Ignite Creation Date:
2025-12-24 @ 4:55 PM
Ignite Modification Date:
2025-12-28 @ 1:24 PM
Study NCT ID:
NCT05032950
Status:
COMPLETED
Last Update Posted:
2023-10-04
First Post:
2021-08-27
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Drug-Drug Interaction Study to Estimate the Effect of PF-07321332/Ritonavir and Ritonavir on Midazolam in Healthy Participants
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000086382', 'term': 'COVID-19'}, {'id': 'D045169', 'term': 'Severe Acute Respiratory Syndrome'}], 'ancestors': [{'id': 'D011024', 'term': 'Pneumonia, Viral'}, {'id': 'D011014', 'term': 'Pneumonia'}, {'id': 'D012141', 'term': 'Respiratory Tract Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D018352', 'term': 'Coronavirus Infections'}, {'id': 'D003333', 'term': 'Coronaviridae Infections'}, {'id': 'D030341', 'term': 'Nidovirales Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008874', 'term': 'Midazolam'}, {'id': 'C000718217', 'term': 'nirmatrelvir'}, {'id': 'D019438', 'term': 'Ritonavir'}], 'ancestors': [{'id': 'D001569', 'term': 'Benzodiazepines'}, {'id': 'D001552', 'term': 'Benzazepines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D013844', 'term': 'Thiazoles'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'ClinicalTrials.gov_Inquiries@pfizer.com', 'phone': '1-800-718-1021', 'title': 'Pfizer ClinicalTrials.gov Call Center', 'organization': 'Pfizer Inc.'}, 'certainAgreement': {'piSponsorEmployee': True, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'Baseline up to Day 28', 'eventGroups': [{'id': 'EG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 4, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5', 'otherNumAtRisk': 11, 'deathsNumAtRisk': 11, 'otherNumAffected': 9, 'seriousNumAtRisk': 11, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Ritonavir 100 mg + Midazolam 2 mg', 'description': 'Ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5', 'otherNumAtRisk': 11, 'deathsNumAtRisk': 11, 'otherNumAffected': 7, 'seriousNumAtRisk': 11, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Nodal rhythm', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Abdominal discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Dry mouth', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Dyspepsia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Haematochezia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Chest discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Vessel puncture site pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Vessel puncture site reaction', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Folliculitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Dysgeusia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 6}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Somnolence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 3}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Nightmare', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Heavy menstrual bleeding', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}], 'organSystem': 'Reproductive system and breast disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Vaginal haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}], 'organSystem': 'Reproductive system and breast disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Dry throat', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Rhinorrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}, {'term': 'Rash maculo-papular', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 24.1'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Maximum Plasma Concentration (Cmax) of Midazolam When Administered Alone and With PF-07321332/Ritonavir', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'categories': [{'measurements': [{'value': '9.812', 'spread': '38', 'groupId': 'OG000'}, {'value': '36.18', 'spread': '17', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Reference/Test Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '368.33', 'ciLowerLimit': '318.91', 'ciUpperLimit': '425.41', 'groupDescription': 'Natural log-transformed Cmax of midazolam was analyzed using mixed effect model with treatment, period and sequence as fixed effects and participant in sequence as random effect. Estimates of the adjusted mean differences (AMD) (Test-Reference) and 90%CIs were obtained from the model. The AMD and 90%CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90%CI for the ratios.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'Cmax for midazolam following single dose administration with and without PF-07321332/ritonavir was observed directly from data. Natural log-transformed Cmax for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam \\[test\\]/midazolam \\[reference\\] and 90% CIs) were expressed as percentages.', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.'}, {'type': 'PRIMARY', 'title': 'Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinity Time (AUCinf) of Midazolam When Administered Alone and With PF-07321332/Ritonavir', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'categories': [{'measurements': [{'value': '26.13', 'spread': '45', 'groupId': 'OG000'}, {'value': '363.9', 'spread': '13', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Reference/Test Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1430.02', 'ciLowerLimit': '1204.54', 'ciUpperLimit': '1697.71', 'groupDescription': 'Natural log-transformed AUCinf of midazolam was analyzed using mixed effect model with treatment, period and sequence as fixed effects and participant in sequence as random effect. Estimates of the adjusted mean differences (AMD) (Test-Reference) and 90%CIs were obtained from the model. The AMD and 90%CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90%CI for the ratios.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'AUCinf for midazolam following single dose administration with and without PF-07321332/ritonavir was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. Natural log-transformed AUCinf for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam \\[test\\]/midazolam \\[reference\\] and 90% CIs) were expressed as percentages.', 'unitOfMeasure': 'ng*hr/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.'}, {'type': 'PRIMARY', 'title': 'Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Midazolam When Administered Alone and With PF-07321332/Ritonavir', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'categories': [{'measurements': [{'value': '25.02', 'spread': '44', 'groupId': 'OG000'}, {'value': '353.8', 'spread': '13', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Test/Reference Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1451.78', 'ciLowerLimit': '1224.42', 'ciUpperLimit': '1721.35', 'groupDescription': 'Natural log-transformed AUClast of midazolam was analyzed using mixed effect model with treatment, period and sequence as fixed effects and participant in sequence as random effect. Estimates of the adjusted mean differences (AMD) (Test-Reference) and 90%CIs were obtained from the model. The AMD and 90%CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90%CI for the ratios.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'AUClast for midazolam following single dose administration with and without PF-07321332/ritonavir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam \\[test\\]/midazolam \\[reference\\] and 90% CIs) were expressed as percentages.', 'unitOfMeasure': 'ng*hr/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Treatment-emergent Adverse Events (TEAEs)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}, {'value': '11', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}, {'id': 'OG002', 'title': 'Ritonavir 100 mg + Midazolam 2 mg', 'description': 'Participants administer Ritonavir orally every 12 hours for a total of 9 doses on Day1-5 and Midazolam orally as a single dose on Day 5, followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).'}], 'classes': [{'title': 'Participants with adverse events (All Causalities)', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '9', 'groupId': 'OG001'}, {'value': '7', 'groupId': 'OG002'}]}]}, {'title': 'Participants with adverse events (Treatment related)', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '9', 'groupId': 'OG001'}, {'value': '7', 'groupId': 'OG002'}]}]}, {'title': 'Participants with serious adverse events', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'Participants with severe adverse events', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline up to Day 28', 'description': 'An adverse event was considered a TEAE if the event started during the effective duration of treatment. All events that start on or after the first dosing day and time/ start time, if collected, but before the last dose plus the lag time (28 days) were flagged as TEAEs. The algorithm did consider any events that started prior to the first dose date. Any events occurring following start of treatment or increasing in severity were counted as treatment emergent. Events that occur in a non-treatment period (for example, Washout or Follow-up) were counted as treatment emergent and attributed to the previous treatment taken.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants randomly assigned to study intervention and who take at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Laboratory Abnormalities', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}, {'value': '11', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}, {'id': 'OG002', 'title': 'Ritonavir 100 mg + Midazolam 2 mg', 'description': 'Ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'title': 'HEMATOLOGY - Lymphocytes/Leukocytes (%) >1.2x ULN', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '1', 'groupId': 'OG002'}]}]}, {'title': 'HEMATOLOGY - Neutrophils (10^3/mm^3) <0.8x LLN', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '1', 'groupId': 'OG002'}]}]}, {'title': 'HEMATOLOGY - Neutrophils/Leukocytes (%) <0.8x LLN', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '1', 'groupId': 'OG002'}]}]}, {'title': 'HEMATOLOGY - Eosinophils/Leukocytes (%) >1.2x ULN', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '1', 'groupId': 'OG002'}]}]}, {'title': 'HEMATOLOGY - Monocytes/Leukocytes (%) >1.2x ULN', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '2', 'groupId': 'OG002'}]}]}, {'title': 'HEMATOLOGY - Prothrombin Time (sec) >1.1x ULN', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '1', 'groupId': 'OG002'}]}]}, {'title': 'CLINICAL CHEMISTRY - Thyrotropin (uIU/mL) <0.8x LLN', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '1', 'groupId': 'OG002'}]}]}, {'title': 'CLINICAL CHEMISTRY - Fibrinogen (mg/dL) >1.25x Baseline', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'URINALYSIS - URINE Hemoglobin (Scalar) ≥1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '3', 'groupId': 'OG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline up to Day 28', 'description': "The haematological, clinical chemistry (serum) and urinalysis safety tests were assessed against the criteria specified in the sponsor reporting standards to determine if there were any clinically significant laboratory abnormalities. The assessment took into account whether each participant's baseline test result was within or outside the laboratory reference range for the particular laboratory parameter. Baseline was defined as the last planned predose measurement taken in each study period.", 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Vital Signs Abnormalities', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}, {'value': '11', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}, {'id': 'OG002', 'title': 'Ritonavir 100 mg + Midazolam 2 mg', 'description': 'Ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline up to Day 28', 'description': 'Baseline was the last predose recording in each study period. Only post baseline values are included in this analysis', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Electrocardiogram (ECG) Abnormalities', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}, {'value': '11', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}, {'id': 'OG002', 'title': 'Ritonavir 100 mg + Midazolam 2 mg', 'description': 'Ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'title': 'PR INTERVAL, AGGREGATE (MSEC) - Value≥300', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'PR INTERVAL, AGGREGATE (MSEC) - %Change≥25/50%', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'QRS DURATION, AGGREGATE (MSEC) - Value≥140', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'QRS DURATION, AGGREGATE (MSEC) - %Change≥50%', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'QTCF INTERVAL, AGGREGATE (MSEC) - 450<Value≤480', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'QTCF INTERVAL, AGGREGATE (MSEC) - 480<Value≤500', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'QTCF INTERVAL, AGGREGATE (MSEC) - Value>500', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'QTCF INTERVAL, AGGREGATE (MSEC) - 30<Change≤60', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'QTCF INTERVAL, AGGREGATE (MSEC) - Change>60', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline up to Day 28', 'description': 'Baseline and changes from baseline in PR, QT, QRS, heart rate and QTcF were summarized by treatment and time postdose. Baseline was defined as the average of the triplicate predose recordings in each study period. ECG endpoints and changes from baseline (QTcF, PR, QRS), over all measurements taken postdose, were also summarized descriptively by treatment using categories as defined in the Criteria for Safety Values of Potential Clinical Concern appendix of the protocol and for QTc values corresponding to ICH E14 thresholds, which are: QTcF (msec): 450\\<value≤480; 480\\<value≤500; \\>500; QTcF (msec) increase from baseline: 30\\<change≤60; change\\>60', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.'}, {'type': 'SECONDARY', 'title': 'Cmax of Midazolam When Administered Alone and With Ritonavir', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'Ritonavir 100 mg + Midazolam 2 mg', 'description': 'ritonavir: Administered orally every 12 hours for a total of 9 doses on Day1-5.\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'categories': [{'measurements': [{'value': '9.812', 'spread': '38', 'groupId': 'OG000'}, {'value': '38.03', 'spread': '18', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Test/Reference Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '387.20', 'ciLowerLimit': '335.25', 'ciUpperLimit': '447.21', 'groupDescription': 'Natural log-transformed Cmax of midazolam was analyzed using mixed effect model with treatment, period and sequence as fixed effects and participant in sequence as random effect. Estimates of the adjusted mean differences (AMD)(Test-Reference) and 90%CIs were obtained from the model. The AMD and 90%CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90%CI for the ratios.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'Cmax for midazolam following single dose administration with and without ritonavir was observed directly form data. Natural log-transformed Cmax for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (ritonavir + midazolam \\[test\\]/midazolam \\[reference\\] and 90% CIs) were expressed as percentages.', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.'}, {'type': 'SECONDARY', 'title': 'AUCinf of Midazolam When Administered Alone and With Ritonavir', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'Ritonavir 100 mg + Midazolam 2 mg', 'description': 'Ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Day1-5.\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'categories': [{'measurements': [{'value': '26.13', 'spread': '45', 'groupId': 'OG000'}, {'value': '418.6', 'spread': '15', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Test/Reference Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1645.15', 'ciLowerLimit': '1385.75', 'ciUpperLimit': '1953.11', 'groupDescription': 'Natural log-transformed AUCinf of midazolam was analyzed using mixed effect model with treatment, period and sequence as fixed effects and participant in sequence as random effect. Estimates of the adjusted mean differences (AMD)(Test-Reference) and 90%CIs were obtained from the model. The AMD and 90%CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90%CI for the ratios', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'AUCinf for midazolam following single dose administration with and without ritonavir was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. Natural log-transformed AUCinf for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (ritonavir + midazolam \\[test\\]/midazolam \\[reference\\] and 90% CIs) were expressed as percentages.', 'unitOfMeasure': 'ng*hr/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.'}, {'type': 'SECONDARY', 'title': 'AUClast of Midazolam When Administered Alone and With Ritonavir', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'Ritonavir 100 mg + Midazolam 2 mg', 'description': 'Ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'categories': [{'measurements': [{'value': '25.02', 'spread': '44', 'groupId': 'OG000'}, {'value': '408.8', 'spread': '15', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Test/Reference Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1677.25', 'ciLowerLimit': '1414.59', 'ciUpperLimit': '1988.69', 'groupDescription': 'Natural log-transformed AUClast of midazolam was analyzed using mixed effect model with treatment, period and sequence as fixed effects and participant in sequence as random effect. Estimates of the adjusted mean differences (AMD)(Test-Reference) and 90%CIs were obtained from the model. The AMD and 90%CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90%CI for the ratios.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam/ritonavir: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose', 'description': 'AUClast for midazolam following single dose administration with and without ritonavir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (ritonavir + midazolam \\[test\\]/midazolam \\[reference\\] and 90% CIs) were expressed as percentages.', 'unitOfMeasure': 'ng*hr/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.'}, {'type': 'SECONDARY', 'title': 'Apparent Clearance (CL/F) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}, {'value': '10', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}, {'id': 'OG002', 'title': 'Ritonavir 100mg+ Midazolam 2mg', 'description': 'Ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'categories': [{'measurements': [{'value': '76.57', 'spread': '45', 'groupId': 'OG000'}, {'value': '5.500', 'spread': '13', 'groupId': 'OG001'}, {'value': '4.776', 'spread': '15', 'groupId': 'OG002'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'CL/F for midazolam following single dose administration with and without PF-07321332/ritonavir or ritonavir was calculated by Dose/AUCinf.', 'unitOfMeasure': 'Litre/hour', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.'}, {'type': 'SECONDARY', 'title': 'Apparent Volume of Distribution (Vz/F) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}, {'value': '10', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}, {'id': 'OG002', 'title': 'Ritonavir 100mg+ Midazolam 2mg', 'description': 'Ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'categories': [{'measurements': [{'value': '488.6', 'spread': '48', 'groupId': 'OG000'}, {'value': '79.84', 'spread': '28', 'groupId': 'OG001'}, {'value': '76.43', 'spread': '31', 'groupId': 'OG002'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'Vz/F for midazolam following single dose administration with and without PF-07321332/ritonavir or ritonavir was calculated by Dose/(AUCinf • kel).', 'unitOfMeasure': 'Litre', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.'}, {'type': 'SECONDARY', 'title': 'Time for Cmax (Tmax) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}, {'value': '10', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}, {'id': 'OG002', 'title': 'Ritonavir 100mg+ Midazolam 2mg', 'description': 'Ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'categories': [{'measurements': [{'value': '1.00', 'groupId': 'OG000', 'lowerLimit': '0.500', 'upperLimit': '1.10'}, {'value': '1.00', 'groupId': 'OG001', 'lowerLimit': '0.500', 'upperLimit': '1.05'}, {'value': '1.02', 'groupId': 'OG002', 'lowerLimit': '0.500', 'upperLimit': '3.17'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'Tmax for midazolam following single dose administration with and without PF-07321332/ritonavir or ritonavir was calculated by observed directly from data as time of first occurrence.', 'unitOfMeasure': 'Hour', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.'}, {'type': 'SECONDARY', 'title': 'Terminal Half-life (t1/2) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}, {'value': '10', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam 2 mg', 'description': 'Midazolam administered as a single dose on Day 1'}, {'id': 'OG001', 'title': 'PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}, {'id': 'OG002', 'title': 'Ritonavir 100 mg + Midazolam 2 mg', 'description': 'Ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5'}], 'classes': [{'categories': [{'measurements': [{'value': '4.988', 'spread': '2.2058', 'groupId': 'OG000'}, {'value': '10.47', 'spread': '2.9096', 'groupId': 'OG001'}, {'value': '11.54', 'spread': '3.4741', 'groupId': 'OG002'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 't½ for midazolam following single dose administration with and without PF-07321332/ritonavir or ritonavir was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear.', 'unitOfMeasure': 'Hour', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Treatment Sequence 1', 'description': 'Period 1: Treatment A: Midazolam Single dose of 2 mg midazolam was administered orally on Day 1, followed by serial PK sampling and 2-day washout (Duration: Day 1 to Day 3).\n\nPeriod 2: Treatment B: PF-07321332/Ritonavir + Midazolam PF-07321332 300 mg/ritonavir 100 mg was administered orally every 12 hours for a total of 9 doses on Days 1-5 and a single oral dose of midazolam 2 mg was administered on Day 5 followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).\n\nPeriod 3: Treatment C: Ritonavir + Midazolam Ritonavir 100 mg was administered orally every 12 hours for a total of 9 doses on Days 1-5 and a single oral dose of midazolam 2 mg was administered on Day 5 followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).'}, {'id': 'FG001', 'title': 'Treatment Sequence 2', 'description': 'Period 1: Treatment C: Ritonavir + Midazolam Ritonavir 100 mg was administered orally every 12 hours for a total of 9 doses on Days 1-5 and a single oral dose of midazolam 2 mg was administered on Day 5 followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).\n\nPeriod 2: Treatment A: Midazolam Single dose of 2 mg midazolam was administered orally on Day 1, followed by serial PK sampling and 2-day washout (Duration: Day 1 to Day 3).\n\nPeriod 3: Treatment B: PF-07321332/Ritonavir + Midazolam PF-07321332 300 mg/ritonavir 100 mg was administered orally every 12 hours for a total of 9 doses on Days 1-5 and a single oral dose of midazolam 2 mg was administered on Day 5 followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).'}, {'id': 'FG002', 'title': 'Treatment Sequence 3', 'description': 'Period 1: Treatment B: PF-07321332/Ritonavir + Midazolam PF-07321332 300 mg/ritonavir 100 mg was administered orally every 12 hours for a total of 9 doses on Days 1-5 and a single oral dose of midazolam 2 mg was administered on Day 5 followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).\n\nPeriod 2: Treatment C: Ritonavir + Midazolam Ritonavir 100 mg was administered orally every 12 hours for a total of 9 doses on Days 1-5 and a single oral dose of midazolam 2 mg was administered on Day 5 followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).\n\nPeriod 3: Treatment A: Midazolam Single dose of 2 mg midazolam was administered orally on Day 1, followed by serial PK sampling and 2-day washout (Duration: Day 1 to Day 3).'}, {'id': 'FG003', 'title': 'Treatment Sequence 4', 'description': 'Period 1: Treatment C: Ritonavir + Midazolam Ritonavir 100 mg was administered orally every 12 hours for a total of 9 doses on Days 1-5 and a single oral dose of midazolam 2 mg was administered on Day 5 followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).\n\nPeriod 2: Treatment B: PF-07321332/Ritonavir + Midazolam PF-07321332 300 mg/ritonavir 100 mg was administered orally every 12 hours for a total of 9 doses on Days 1-5 and a single oral dose of midazolam 2 mg was administered on Day 5 followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).\n\nPeriod 3: Treatment A: Midazolam Single dose of 2 mg midazolam administered orally on Day 1, followed by serial PK sampling and 2-day washout (Duration: Day 1 to Day 3).'}, {'id': 'FG004', 'title': 'Treatment Sequence 5', 'description': 'Period 1: Treatment B: PF-07321332/Ritonavir + Midazolam PF-07321332 300 mg/ritonavir 100 mg was administered orally every 12 hours for a total of 9 doses on Days 1-5 and a single oral dose of midazolam 2 mg was administered on Day 5 followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).\n\nPeriod 2: Treatment A: Midazolam Single dose of 2 mg midazolam was administered orally on Day 1, followed by serial PK sampling and 2-day washout (Duration: Day 1 to Day 3).\n\nPeriod 3: Treatment C: Ritonavir + Midazolam Ritonavir 100 mg was administered orally every 12 hours for a total of 9 doses on Days 1-5 and a single oral dose of midazolam 2 mg was administered on Day 5 followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).'}, {'id': 'FG005', 'title': 'Treatment Sequence 6', 'description': 'Period 1: Treatment A: Midazolam Single dose of 2 mg midazolam was administered orally on Day 1, followed by serial PK sampling and 2-day washout (Duration: Day 1 to Day 3).\n\nPeriod 2: Treatment C: Ritonavir + Midazolam Ritonavir 100 mg was administered orally every 12 hours for a total of 9 doses on Days 1-5 and a single oral dose of midazolam 2 mg was administered on Day 5 followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).\n\nPeriod 3: Treatment B: PF-07321332/Ritonavir + Midazolam PF-07321332 300 mg/ritonavir 100 mg was administered orally every 12 hours for a total of 9 doses on Days 1-5 and a single oral dose of midazolam 2 mg was administered on Day 5 followed by serial PK sampling and a 7-day washout (Duration: Day 1 to Day 12).'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'comment': 'Assigned to Treatment', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '2'}, {'groupId': 'FG002', 'numSubjects': '2'}, {'groupId': 'FG003', 'numSubjects': '2'}, {'groupId': 'FG004', 'numSubjects': '2'}, {'groupId': 'FG005', 'numSubjects': '2'}]}, {'type': 'COMPLETED', 'comment': 'Completed', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '2'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '1'}, {'groupId': 'FG004', 'numSubjects': '2'}, {'groupId': 'FG005', 'numSubjects': '2'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '1'}, {'groupId': 'FG004', 'numSubjects': '0'}, {'groupId': 'FG005', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '1'}, {'groupId': 'FG004', 'numSubjects': '0'}, {'groupId': 'FG005', 'numSubjects': '0'}]}]}], 'preAssignmentDetails': 'A total of 12 healthy participants were randomized to receive midazolam, PF-07321332/ritonavir + midazolam, and ritonavir + midazolam in a total of 6 sequences.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'All Participants', 'description': 'All participants enrolled in this study'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'title': 'Mean (SD)', 'categories': [{'measurements': [{'value': '34.6', 'spread': '9.26', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Age, Customized', 'classes': [{'title': '<18 Years', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': '18-25 Years', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}, {'title': '26-35 Years', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}, {'title': '36-45 Years', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}, {'title': '>45 Years', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '11', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'White', 'categories': [{'measurements': [{'value': '9', 'groupId': 'BG000'}]}]}, {'title': 'Black or African American', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}, {'title': 'Asian', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'Hispanic or Latino', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}, {'title': 'Not Hispanic or Latino', 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-07-23', 'size': 3914765, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2022-11-30T17:21', 'hasProtocol': True}, {'date': '2021-08-30', 'size': 2599223, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2022-11-30T17:21', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'This is a Phase I, crossover, 3-treatment, 6-sequence study to evaluate the effect of PF-07321332/ritonavir and ritonavir on the PK of midazolam in healthy participants. Midazolam is a substrate for CYP3A4. A total of approximately 12 healthy male and/or female participants will be enrolled into the study.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 12}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-09-17', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-12', 'completionDateStruct': {'date': '2021-12-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-12-01', 'studyFirstSubmitDate': '2021-08-27', 'resultsFirstSubmitDate': '2022-12-01', 'studyFirstSubmitQcDate': '2021-08-27', 'lastUpdatePostDateStruct': {'date': '2023-10-04', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2022-12-01', 'studyFirstPostDateStruct': {'date': '2021-09-02', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2023-10-04', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-12-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maximum Plasma Concentration (Cmax) of Midazolam When Administered Alone and With PF-07321332/Ritonavir', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'Cmax for midazolam following single dose administration with and without PF-07321332/ritonavir was observed directly from data. Natural log-transformed Cmax for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam \\[test\\]/midazolam \\[reference\\] and 90% CIs) were expressed as percentages.'}, {'measure': 'Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinity Time (AUCinf) of Midazolam When Administered Alone and With PF-07321332/Ritonavir', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'AUCinf for midazolam following single dose administration with and without PF-07321332/ritonavir was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. Natural log-transformed AUCinf for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam \\[test\\]/midazolam \\[reference\\] and 90% CIs) were expressed as percentages.'}, {'measure': 'Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Midazolam When Administered Alone and With PF-07321332/Ritonavir', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'AUClast for midazolam following single dose administration with and without PF-07321332/ritonavir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam \\[test\\]/midazolam \\[reference\\] and 90% CIs) were expressed as percentages.'}], 'secondaryOutcomes': [{'measure': 'Number of Participants With Treatment-emergent Adverse Events (TEAEs)', 'timeFrame': 'Baseline up to Day 28', 'description': 'An adverse event was considered a TEAE if the event started during the effective duration of treatment. All events that start on or after the first dosing day and time/ start time, if collected, but before the last dose plus the lag time (28 days) were flagged as TEAEs. The algorithm did consider any events that started prior to the first dose date. Any events occurring following start of treatment or increasing in severity were counted as treatment emergent. Events that occur in a non-treatment period (for example, Washout or Follow-up) were counted as treatment emergent and attributed to the previous treatment taken.'}, {'measure': 'Number of Participants With Laboratory Abnormalities', 'timeFrame': 'Baseline up to Day 28', 'description': "The haematological, clinical chemistry (serum) and urinalysis safety tests were assessed against the criteria specified in the sponsor reporting standards to determine if there were any clinically significant laboratory abnormalities. The assessment took into account whether each participant's baseline test result was within or outside the laboratory reference range for the particular laboratory parameter. Baseline was defined as the last planned predose measurement taken in each study period."}, {'measure': 'Number of Participants With Vital Signs Abnormalities', 'timeFrame': 'Baseline up to Day 28', 'description': 'Baseline was the last predose recording in each study period. Only post baseline values are included in this analysis'}, {'measure': 'Number of Participants With Electrocardiogram (ECG) Abnormalities', 'timeFrame': 'Baseline up to Day 28', 'description': 'Baseline and changes from baseline in PR, QT, QRS, heart rate and QTcF were summarized by treatment and time postdose. Baseline was defined as the average of the triplicate predose recordings in each study period. ECG endpoints and changes from baseline (QTcF, PR, QRS), over all measurements taken postdose, were also summarized descriptively by treatment using categories as defined in the Criteria for Safety Values of Potential Clinical Concern appendix of the protocol and for QTc values corresponding to ICH E14 thresholds, which are: QTcF (msec): 450\\<value≤480; 480\\<value≤500; \\>500; QTcF (msec) increase from baseline: 30\\<change≤60; change\\>60'}, {'measure': 'Cmax of Midazolam When Administered Alone and With Ritonavir', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'Cmax for midazolam following single dose administration with and without ritonavir was observed directly form data. Natural log-transformed Cmax for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (ritonavir + midazolam \\[test\\]/midazolam \\[reference\\] and 90% CIs) were expressed as percentages.'}, {'measure': 'AUCinf of Midazolam When Administered Alone and With Ritonavir', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'AUCinf for midazolam following single dose administration with and without ritonavir was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. Natural log-transformed AUCinf for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (ritonavir + midazolam \\[test\\]/midazolam \\[reference\\] and 90% CIs) were expressed as percentages.'}, {'measure': 'AUClast of Midazolam When Administered Alone and With Ritonavir', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam/ritonavir: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose', 'description': 'AUClast for midazolam following single dose administration with and without ritonavir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (ritonavir + midazolam \\[test\\]/midazolam \\[reference\\] and 90% CIs) were expressed as percentages.'}, {'measure': 'Apparent Clearance (CL/F) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'CL/F for midazolam following single dose administration with and without PF-07321332/ritonavir or ritonavir was calculated by Dose/AUCinf.'}, {'measure': 'Apparent Volume of Distribution (Vz/F) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'Vz/F for midazolam following single dose administration with and without PF-07321332/ritonavir or ritonavir was calculated by Dose/(AUCinf • kel).'}, {'measure': 'Time for Cmax (Tmax) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 'Tmax for midazolam following single dose administration with and without PF-07321332/ritonavir or ritonavir was calculated by observed directly from data as time of first occurrence.'}, {'measure': 'Terminal Half-life (t1/2) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir', 'timeFrame': 'Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose', 'description': 't½ for midazolam following single dose administration with and without PF-07321332/ritonavir or ritonavir was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear.'}]}, 'oversightModule': {'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Drug-drug interaction', 'Midazolam', 'COVID-19 (Coronavirus disease 2019)', 'SARS-CoV (severe acute respiratory syndrome coronavirus)'], 'conditions': ['Healthy Participants']}, 'referencesModule': {'references': [{'pmid': '37354048', 'type': 'DERIVED', 'citation': 'Cox DS, Rehman M, Khan T, Ginman K, Salageanu J, LaBadie RR, Wan K, Damle B. Effects of nirmatrelvir/ritonavir on midazolam and dabigatran pharmacokinetics in healthy participants. Br J Clin Pharmacol. 2023 Nov;89(11):3352-3363. doi: 10.1111/bcp.15835. Epub 2023 Jul 12.'}, {'pmid': '37231296', 'type': 'DERIVED', 'citation': 'Sagawa K, Lin J, Jaini R, Di L. Physiologically-Based Pharmacokinetic Modeling of PAXLOVID with First-Order Absorption Kinetics. Pharm Res. 2023 Aug;40(8):1927-1938. doi: 10.1007/s11095-023-03538-5. Epub 2023 May 25.'}], 'seeAlsoLinks': [{'url': 'https://pmiform.com/clinical-trial-info-request?StudyID=C4671013', 'label': 'To obtain contact information for a study center near you, click here.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to estimate the effect PF-07321332/Ritonavir and Ritonavir on Midazolam (a cytochrome P450 \\[CYP\\]3A4 substrate) in Healthy Adult Participants.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Female participants of childbearing potential must have a negative (urine or serum) pregnancy test.\n2. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \\>50 kg (110 lb).\n\n \\-\n\nExclusion Criteria:\n\n1. Positive test result for SARS-CoV-2 infection at the time of Screening or Day -1.\n2. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).\n3. Clinically relevant abnormalities requiring treatment (eg, acute myocardial infarction, unstable ischemic conditions, evidence of ventricular dysfunction, serious tachy or brady arrhythmias) or indicating serious underlying heart disease (eg, prolonged PR interval, cardiomyopathy, heart failure greater than New York Heart Association (NYHA) 1, underlying structural heart disease, Wolff Parkinson-White syndrome).\n4. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).\n5. History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or hepatitis C virus (HCVAb). Hepatitis B vaccination is allowed.\n6. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic (eg, Contact with positive case, residence, or travel to an area with high incidence) that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study."}, 'identificationModule': {'nctId': 'NCT05032950', 'briefTitle': 'Drug-Drug Interaction Study to Estimate the Effect of PF-07321332/Ritonavir and Ritonavir on Midazolam in Healthy Participants', 'organization': {'class': 'INDUSTRY', 'fullName': 'Pfizer'}, 'officialTitle': 'COVID-19: A PHASE 1, OPEN-LABEL, 3-TREATMENT, 6-SEQUENCE, 3-PERIOD CROSSOVER STUDY TO ESTIMATE THE EFFECT OF PF-07321332/RITONAVIR AND RITONAVIR ON THE PHARMACOKINETICS OF MIDAZOLAM IN HEALTHY PARTICIPANTS.', 'orgStudyIdInfo': {'id': 'C4671013'}, 'secondaryIdInfos': [{'id': '2021-003590-62', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Treatment A', 'description': 'Midazolam orally', 'interventionNames': ['Drug: Midazolam']}, {'type': 'EXPERIMENTAL', 'label': 'Treatment B', 'description': 'PF-07321332/ritonavir orally + Midazolam orally', 'interventionNames': ['Drug: PF-07321332/ritonavir + Midazolam']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Treatment C', 'description': 'Ritonavir orally + Midazolam orally', 'interventionNames': ['Drug: Ritonavir + Midazolam']}], 'interventions': [{'name': 'Midazolam', 'type': 'DRUG', 'description': 'Midazolam administered as a single dose on Day 1', 'armGroupLabels': ['Treatment A']}, {'name': 'PF-07321332/ritonavir + Midazolam', 'type': 'DRUG', 'description': 'PF-07321332/ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Days 1-5\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5', 'armGroupLabels': ['Treatment B']}, {'name': 'Ritonavir + Midazolam', 'type': 'DRUG', 'description': 'Ritonavir:\n\nAdministered orally every 12 hours for a total of 9 doses on Day1-5.\n\nMidazolam:\n\nAdministered orally as a single dose on Day 5', 'armGroupLabels': ['Treatment C']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'B-1070', 'city': 'Brussels', 'state': 'Bruxelles-capitale, Région de', 'country': 'Belgium', 'facility': 'Brussels Clinical Research Unit', 'geoPoint': {'lat': 50.85045, 'lon': 4.34878}}], 'overallOfficials': [{'name': 'Pfizer CT.gov Call Center', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Pfizer'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': "Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\\_trials/trial\\_data\\_and\\_results/data\\_requests."}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Pfizer', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}