Ignite Creation Date:
2025-12-25 @ 2:55 AM
Ignite Modification Date:
2026-01-05 @ 11:44 PM
Study NCT ID:
NCT03726333
Status:
TERMINATED
Last Update Posted:
2024-06-21
First Post:
2018-09-24
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Hepatic Impairment Study for Lorlatinib in Cancer Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008175', 'term': 'Lung Neoplasms'}], 'ancestors': [{'id': 'D012142', 'term': 'Respiratory Tract Neoplasms'}, {'id': 'D013899', 'term': 'Thoracic Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000590786', 'term': 'lorlatinib'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'ClinicalTrials_gov_Inquiries@pfizer.com', 'phone': '1-800-718-1021', 'title': 'Pfizer ClinicalTrials.gov Call Center', 'organization': 'Pfizer Inc.'}, 'certainAgreement': {'otherDetails': 'Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}, 'limitationsAndCaveats': {'description': 'The study was terminated due to difficulties with enrolling eligible patients. Only 1 participant was enrolled in this study. Outcome measures and AE data were not reported as planned in the protocol because doing so would risk re-dentification of the individual participant.'}}, 'adverseEventsModule': {'timeFrame': 'From Screening (within 28 days prior to Cycle 1 Day 1) through and including at least 28 days after after the last lorlatinib dose. The duration is approximately 42 days.', 'description': 'AE information were reported by using the System Organ Class instead of preferred term to avoid the risk of re-identification of the participant.', 'eventGroups': [{'id': 'EG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.', 'otherNumAtRisk': 1, 'deathsNumAtRisk': 1, 'otherNumAffected': 1, 'seriousNumAtRisk': 1, 'deathsNumAffected': 0, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'General disorders', 'stats': [{'groupId': 'EG000', 'numAtRisk': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v24.1'}, {'term': 'Metabolism and nutrition disorders', 'stats': [{'groupId': 'EG000', 'numAtRisk': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v24.1'}, {'term': 'Nervous system disorders', 'stats': [{'groupId': 'EG000', 'numAtRisk': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v24.1'}, {'term': 'Psychiatric disorders', 'stats': [{'groupId': 'EG000', 'numAtRisk': 1, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v24.1'}], 'seriousEvents': [{'term': 'Nervous system disorders', 'stats': [{'groupId': 'EG000', 'numAtRisk': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v24.1'}, {'term': 'Psychiatric disorders', 'stats': [{'groupId': 'EG000', 'numAtRisk': 1, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v24.1'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Area Under Plasma Lorlatinib Concentration-Time Curve From Time 0 to Dosing Interval of 24 Hours (AUC24) at Steady State On Cycle 2 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'AUC24 was defined as area under the plasma concentration time profile during 1 dosing interval (24 hours).', 'unitOfMeasure': 'nanogram*hour per milliliter (ng*hr/mL)', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'PRIMARY', 'title': 'Observed Maximal Plasma Concentration (Cmax) at Steady State on Cycle 2 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant.', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Cmax was defined as maximum plasma concentration and was observed directly from data.', 'unitOfMeasure': 'nanogram per milliliter (ng/mL)', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'title': 'All-causality TEAEs', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of the participant.', 'groupId': 'OG000'}]}]}, {'title': 'Treatment-related TEAEs', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of the participant.', 'groupId': 'OG000'}]}]}, {'title': 'All-causality serious AEs', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of the participant.', 'groupId': 'OG000'}]}]}, {'title': 'Treatment-related serious AEs', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of the participant.', 'groupId': 'OG000'}]}]}, {'title': 'All-causalities AEs ≥Grade 3', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of the participant.', 'groupId': 'OG000'}]}]}, {'title': 'Treatment-related AEs ≥Grade 3', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of the participant.', 'groupId': 'OG000'}]}]}, {'title': 'All-causalities Grade 1 AEs', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of the participant.', 'groupId': 'OG000'}]}]}, {'title': 'Treatment-related Grade 1 AEs', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of the participant.', 'groupId': 'OG000'}]}]}, {'title': 'All-causalities Grade 2 AEs', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of the participant.', 'groupId': 'OG000'}]}]}, {'title': 'Treatment-related Grade 2 AEs', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of the participant.', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'From Screening (within 28 days prior to Cycle 1 Day 1) through and including at least 28 days after after the last lorlatinib dose. The duration is approximately 42 days.', 'description': 'An Adverse event (AE) was any untoward medical occurrence in a participant. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect or that was considered to be an important medical event. AEs were graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. The grades were defined as follows: Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. The focus of AE summaries was on treatment-emergent AE (TEAE). An AE was considered TEAE if the event occurred during the on-treatment period.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib.'}, {'type': 'SECONDARY', 'title': 'Objective Response Rate (ORR)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000', 'lowerLimit': '0', 'upperLimit': '97.5'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Baseline up to approximately 1 year', 'description': 'ORR was defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 relative to the response-evaluable population.', 'unitOfMeasure': 'Percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib.'}, {'type': 'SECONDARY', 'title': 'Duration of Response (DR)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'comment': 'The participant had an overall objective tumor assessment of progressive disease. As no patient responded DR is Not Applicable.', 'groupId': 'OG000', 'lowerLimit': 'NA', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Baseline up to approximately 1 year', 'description': 'DR was measured from the date that an objective tumor response (CR or PR) was first documented (whichever occurred first) to date of objective tumor progression or death due to any cause, whichever occurred first.', 'unitOfMeasure': 'Months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib.'}, {'type': 'SECONDARY', 'title': 'Lorlatinib Area Under Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) After Single Dose on Cycle 1 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'AUClast was defined as area under the plasma concentration time profile from time 0 to the time of the last quantifiable concentration (Clast)', 'unitOfMeasure': 'ng*hr/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'The Time of The Last Quantifiable Concentration (Tlast) of Lorlatinib After Single Dose on Cycle 1 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant', 'groupId': 'OG000', 'lowerLimit': 'NA', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Tlast was defined as the time of the last quantifiable concentration.', 'unitOfMeasure': 'hour', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'The Time to Cmax (Tmax) of Lorlatinib After Single Dose on Cycle 1 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant', 'groupId': 'OG000', 'lowerLimit': 'NA', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Tmax was defined as time for Cmax.', 'unitOfMeasure': 'hour', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Observed Minimal Plasma Concentration (Cmin) at Steady State On Cycle 2 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant.', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Cmin was defined as minimum plasma concentration and was observed directly from data.', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Plasma Lorlatinib AUClast at Steady State On Cycle 2 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant.', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast.', 'unitOfMeasure': 'ng*hr/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Plasma Lorlatinib Tlast at Steady State On Cycle 2 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant', 'groupId': 'OG000', 'lowerLimit': 'NA', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Tlast was defined as the time of the last quantifiable concentration.', 'unitOfMeasure': 'hour', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Apparent Clearance (CL/F) at Steady State On Cycle 2 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant.', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as Dose/AUC24 at steady-state.', 'unitOfMeasure': 'Liter per hour (L/hr)', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Plasma Lorlatinib Metabolite AUC24 at Steady State', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'AUC24 was defined as area under the plasma concentration time profile during one dosing interval (24 hours).', 'unitOfMeasure': 'ng*hr/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Plasma Lorlatinib Metabolite AUClast After Single Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast.', 'unitOfMeasure': 'ng*hr/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Plasma Lorlatinib Metabolite AUClast at Steady State', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast.', 'unitOfMeasure': 'ng*hr/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Plasma Lorlatinib Metabolite Cmax After Single Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant.', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Cmax was defined as maximum plasma concentration and was observed directly from data.', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Plasma Lorlatinib Metabolite Cmax at Steady State', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant.', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Cmax was defined as maximum plasma concentration and was observed directly from data.', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Plasma Lorlatinib Metabolite Tlast After Single Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant.', 'groupId': 'OG000', 'lowerLimit': 'NA', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Tlast was defined as the time of the last quantifiable concentration.', 'unitOfMeasure': 'hour', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Plasma Lorlatinib Metabolite Tlast at Steady State', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant', 'groupId': 'OG000', 'lowerLimit': 'NA', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Tlast was defined as the time of the last quantifiable concentration.', 'unitOfMeasure': 'hour', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Metabolite Ratio of Lorlatinib Metabolite for AUC24 (MRAUC24) at Steady State on Cycle 2 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant.', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'MRAUC24 was defined as metabolite ratio of lorlatinib metabolite for AUC24.', 'unitOfMeasure': 'Ratio', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Metabolite Ratio of Lorlatinib Metabolite for AUClast (MRAUClast) at Steady State on Cycle 2 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant.', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'MRAUClast was defined as metabolite ratio of lorlatinib metabolite for AUClast.', 'unitOfMeasure': 'Ratio', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Metabolite Ratio of Lorlatinib Metabolite for Cmax (MRCmax) at Steady State on Cycle 2 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant.', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'MRCmax was defined as metabolite ratio of lorlatinib metabolite for AUClast.', 'unitOfMeasure': 'Ratio', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}, {'type': 'SECONDARY', 'title': 'Metabolite Ratio of Lorlatinib Metabolite for AUClast (MRAUClast) at Steady State on Cycle 1 Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'spread': 'NA', 'comment': 'No PK parameter estimation was performed for the 1 treated participant.', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'MRAUClast was defined as metabolite ratio of lorlatinib metabolite for AUClast.', 'unitOfMeasure': 'Ratio', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Group A1 Normal Hepatic Function', 'description': 'Continued daily administration of lorlatinib 100 mg in patients with normal hepatic function until disease progression, patient refusal, or unacceptable toxicity occurrence'}, {'id': 'FG001', 'title': 'Group A2 Normal Hepatic Function', 'description': 'Continued daily administration of lorlatinib in patients with normal hepatic function at the dose level same as Group C for the first 22 days and 100 mg once a day (QD) afterwards.'}, {'id': 'FG002', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}, {'id': 'FG003', 'title': 'Group C Moderate Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with moderate hepatic impairment at 50 mg QD initially and may be adjusted based on PK and safety results from the initial several patients.'}, {'id': 'FG004', 'title': 'Group D Severe Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with severe hepatic impairment at the dose level determined based on preliminary PK and safety results from first several patients in Group C.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Progressive Disease', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}]}], 'preAssignmentDetails': 'A total of 4 participants were screened. Among them, 1 participant was enrolled and treated in Group B (mild impairment), 1 participant was eligible for Group A (normal) but not enrolled as Group A was not open for enrolment at that time, and 2 participants were screen failed.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Group B Mild Hepatic Impairment', 'description': 'Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of the participant.', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of the participant..', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': 'NA', 'comment': 'Data cannot be reported because doing so would risk re-identification of participants.', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-11-14', 'size': 3977455, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2022-06-06T15:40', 'hasProtocol': True}, {'date': '2018-08-24', 'size': 1920256, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2022-06-06T15:40', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Patients in the study will be assigned to different groups according to their liver function. Patients in each group will receive specific lorlatinib dose. Plasma samples for pharmacokinetic analysis will be collected in all patients. Safety and efficacy will also be followed in all patients until at least 28 days after the last study treatment.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 1}}, 'statusModule': {'whyStopped': 'The study stopped due to lack of enrollment', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2020-01-14', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-01', 'completionDateStruct': {'date': '2021-07-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-01-11', 'studyFirstSubmitDate': '2018-09-24', 'resultsFirstSubmitDate': '2022-06-06', 'studyFirstSubmitQcDate': '2018-10-29', 'lastUpdatePostDateStruct': {'date': '2024-06-21', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2024-01-11', 'studyFirstPostDateStruct': {'date': '2018-10-31', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2024-06-21', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-07-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Area Under Plasma Lorlatinib Concentration-Time Curve From Time 0 to Dosing Interval of 24 Hours (AUC24) at Steady State On Cycle 2 Day 1', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'AUC24 was defined as area under the plasma concentration time profile during 1 dosing interval (24 hours).'}, {'measure': 'Observed Maximal Plasma Concentration (Cmax) at Steady State on Cycle 2 Day 1', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Cmax was defined as maximum plasma concentration and was observed directly from data.'}], 'secondaryOutcomes': [{'measure': 'Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator', 'timeFrame': 'From Screening (within 28 days prior to Cycle 1 Day 1) through and including at least 28 days after after the last lorlatinib dose. The duration is approximately 42 days.', 'description': 'An Adverse event (AE) was any untoward medical occurrence in a participant. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect or that was considered to be an important medical event. AEs were graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. The grades were defined as follows: Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. The focus of AE summaries was on treatment-emergent AE (TEAE). An AE was considered TEAE if the event occurred during the on-treatment period.'}, {'measure': 'Objective Response Rate (ORR)', 'timeFrame': 'Baseline up to approximately 1 year', 'description': 'ORR was defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 relative to the response-evaluable population.'}, {'measure': 'Duration of Response (DR)', 'timeFrame': 'Baseline up to approximately 1 year', 'description': 'DR was measured from the date that an objective tumor response (CR or PR) was first documented (whichever occurred first) to date of objective tumor progression or death due to any cause, whichever occurred first.'}, {'measure': 'Lorlatinib Area Under Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) After Single Dose on Cycle 1 Day 1', 'timeFrame': 'Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'AUClast was defined as area under the plasma concentration time profile from time 0 to the time of the last quantifiable concentration (Clast)'}, {'measure': 'The Time of The Last Quantifiable Concentration (Tlast) of Lorlatinib After Single Dose on Cycle 1 Day 1', 'timeFrame': 'Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Tlast was defined as the time of the last quantifiable concentration.'}, {'measure': 'The Time to Cmax (Tmax) of Lorlatinib After Single Dose on Cycle 1 Day 1', 'timeFrame': 'Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Tmax was defined as time for Cmax.'}, {'measure': 'Observed Minimal Plasma Concentration (Cmin) at Steady State On Cycle 2 Day 1', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Cmin was defined as minimum plasma concentration and was observed directly from data.'}, {'measure': 'Plasma Lorlatinib AUClast at Steady State On Cycle 2 Day 1', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast.'}, {'measure': 'Plasma Lorlatinib Tlast at Steady State On Cycle 2 Day 1', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Tlast was defined as the time of the last quantifiable concentration.'}, {'measure': 'Apparent Clearance (CL/F) at Steady State On Cycle 2 Day 1', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as Dose/AUC24 at steady-state.'}, {'measure': 'Plasma Lorlatinib Metabolite AUC24 at Steady State', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'AUC24 was defined as area under the plasma concentration time profile during one dosing interval (24 hours).'}, {'measure': 'Plasma Lorlatinib Metabolite AUClast After Single Dose', 'timeFrame': 'Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast.'}, {'measure': 'Plasma Lorlatinib Metabolite AUClast at Steady State', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast.'}, {'measure': 'Plasma Lorlatinib Metabolite Cmax After Single Dose', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Cmax was defined as maximum plasma concentration and was observed directly from data.'}, {'measure': 'Plasma Lorlatinib Metabolite Cmax at Steady State', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Cmax was defined as maximum plasma concentration and was observed directly from data.'}, {'measure': 'Plasma Lorlatinib Metabolite Tlast After Single Dose', 'timeFrame': 'Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Tlast was defined as the time of the last quantifiable concentration.'}, {'measure': 'Plasma Lorlatinib Metabolite Tlast at Steady State', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'Tlast was defined as the time of the last quantifiable concentration.'}, {'measure': 'Metabolite Ratio of Lorlatinib Metabolite for AUC24 (MRAUC24) at Steady State on Cycle 2 Day 1', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'MRAUC24 was defined as metabolite ratio of lorlatinib metabolite for AUC24.'}, {'measure': 'Metabolite Ratio of Lorlatinib Metabolite for AUClast (MRAUClast) at Steady State on Cycle 2 Day 1', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'MRAUClast was defined as metabolite ratio of lorlatinib metabolite for AUClast.'}, {'measure': 'Metabolite Ratio of Lorlatinib Metabolite for Cmax (MRCmax) at Steady State on Cycle 2 Day 1', 'timeFrame': 'Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'MRCmax was defined as metabolite ratio of lorlatinib metabolite for AUClast.'}, {'measure': 'Metabolite Ratio of Lorlatinib Metabolite for AUClast (MRAUClast) at Steady State on Cycle 1 Day 1', 'timeFrame': 'Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.', 'description': 'MRAUClast was defined as metabolite ratio of lorlatinib metabolite for AUClast.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['hepatic impairment', 'lorlatinib', 'cancer', 'pharmacokinetic', 'Lung cancer'], 'conditions': ['Advanced Cancers']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'https://pmiform.com/clinical-trial-info-request?StudyID=B7461009', 'label': 'To obtain contact information for a study center near you, click here.'}]}, 'descriptionModule': {'briefSummary': 'This is a phase 1 study in advanced cancer patients with varied hepatic functions to evaluate the potential effect of hepatic impairment on pharmacokinetics and safety of lorlatinib and provide dose recommendation for patients with hepatic impairment if possible.', 'detailedDescription': 'This will be a Phase 1, open label, multi center, multiple dose, non randomized, Phase 1 clinical trial of lorlatinib in advanced cancer patients with varying degrees of hepatic impairment and necessary age , weight , and gender matched prospect normal hepatic function patients. This study is intended to evaluate the potential effect of hepatic impairments on the PK and safety of lorlatinib after daily administration of lorlatinib and to provide dosing recommendation for patients with varied degree of hepatic impairment if possible.\n\nPatients in the study will be assigned to different groups (A1, normal liver function, control for group B; A2, normal liver function, control for group C; B, mild hepatic impairment; C, moderate hepatic impairment; D, severe hepatic impairment) according to their liver function. The enrollment of approximately 76 advanced cancer patients is anticipated in this study in order to have 8 PK-evaluable patients in each of Groups A1, A2, B and C, and 6 PK-evaluable patients in Group D for final statistical analysis. Evaluable patients are those who complete the planned PK sample collection on Cycle 2 Day 1 and have no lorlatinib dose modification until completion of Cycle 2 Day 1 PK evaluation. Patients who are not evaluable for PK will be replaced. Each patient will be treated with repeated oral once daily doses of lorlatinib in 21-day cycles until disease progression, patient refusal, or unacceptable toxicity occurs. The dose schedule may be modified as necessary for individual patients according to tolerability.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Histologically or cytologically confirmed solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative or palliative measures do not exist, or are no longer effective;\n* Biliary obstruction with a biliary drain or stent;\n* Neurologically stable gliomas and brain metastases;\n* ECOG performance status of 0, 1, or 2;\n* adequate bone marrow function;\n* adequate pancreatic function;\n* adequate renal function;\n* female patients with negative pregnancy test\n\nExclusion Criteria:\n\n* untreated esophageal varices; uncontrolled ascites;\n* episodes of hepatic encephalopathy within the last 4 weeks;\n* spinal cord compression; major surgery within 4 weeks prior to enrollment;\n* radiation therapy within 2 weeks prior to enrollment;\n* last anti-cancer treatment within 2 weeks prior to screening;\n* previous high-dose chemotherapy requiring stem cell rescue;\n* prior to irradiation to \\>25% of the bone marrow;\n* gastrointestinal abnormalities;\n* known prior or suspected hypersensitivity to lorlatinib or lorlatinib tablet;\n* clinically significant bacterial, fungal or viral infections for non-liver cancer patients;\n* clinically significant cardiovascular disease;\n* uncontrolled hypertension; acute pancreatitis with predisposing characteristics;\n* history of grade 3 or 4 interstitial fibrosis or interstitial lung disease;\n* active hemoelysis or evidence of biliary sepsis;\n* prior major gastrointestinal surgery;\n* concurrent use of known strong CYP3A inhibitors, inducers and P-gp substrates with a narrow therapeutic index;\n* concurrent use of CYP3A substrates with narrow therapeutic indices;\n* prior treatment with lorlatinib; active bleeding disorder'}, 'identificationModule': {'nctId': 'NCT03726333', 'briefTitle': 'Hepatic Impairment Study for Lorlatinib in Cancer Patients', 'organization': {'class': 'INDUSTRY', 'fullName': 'Pfizer'}, 'officialTitle': 'A PHASE 1 STUDY TO EVALUATE THE EFFECT OF HEPATIC IMPAIRMENT ON THE PHARMACOKINETICS AND SAFETY OF LORLATINIB IN ADVANCED CANCER PATIENTS', 'orgStudyIdInfo': {'id': 'B7461009'}, 'secondaryIdInfos': [{'id': 'lorlatinib HEPATIC IMPAIRMENT', 'type': 'OTHER', 'domain': 'Alias Study Number'}, {'id': 'HEPATIC IMPAIRMENT', 'type': 'OTHER', 'domain': 'Alias Study Number'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Group A1 Normal hepatic function', 'description': 'continued daily administration of lorlatinib in patients with normal hepatic function', 'interventionNames': ['Drug: lorlatinib']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Group A2 Normal hepatic function', 'description': 'continued daily administration of lorlatinib in patients with normal hepatic function', 'interventionNames': ['Drug: lorlatinib']}, {'type': 'EXPERIMENTAL', 'label': 'Group B mild hepatic impairment', 'description': 'continued daily administration of lorlatinib in patients with mild hepatic impairment', 'interventionNames': ['Drug: lorlatinib']}, {'type': 'EXPERIMENTAL', 'label': 'Group C moderate hepatic impairment', 'description': 'continued daily administration of lorlatinib in patients with moderate hepatic impairment', 'interventionNames': ['Drug: lorlatinib']}, {'type': 'EXPERIMENTAL', 'label': 'Group D severe hepatic impairment', 'description': 'continued daily administration of lorlatinib in patients with severe hepatic impairment', 'interventionNames': ['Drug: lorlatinib']}], 'interventions': [{'name': 'lorlatinib', 'type': 'DRUG', 'description': 'continued daily administration of 100 mg lorlatinib', 'armGroupLabels': ['Group A1 Normal hepatic function']}, {'name': 'lorlatinib', 'type': 'DRUG', 'description': 'continued daily administration of lorlatinib at the dose level same as Group C for the first 22 days and 100 mg QD afterwards', 'armGroupLabels': ['Group A2 Normal hepatic function']}, {'name': 'lorlatinib', 'type': 'DRUG', 'description': 'continued daily administration of 100 mg QD lorlatinib', 'armGroupLabels': ['Group B mild hepatic impairment']}, {'name': 'lorlatinib', 'type': 'DRUG', 'description': 'continued daily administration of lorlatinib at 50 mg QD initially and may be adjusted based on PK and safety results from the initial several patients', 'armGroupLabels': ['Group C moderate hepatic impairment']}, {'name': 'lorlatinib', 'type': 'DRUG', 'description': 'continued daily administration of lorlatinib at the dose level determined based on preliminary PK and safety results from first several patients in Group C', 'armGroupLabels': ['Group D severe hepatic impairment']}]}, 'contactsLocationsModule': {'locations': [{'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': 'University of Colorado Denver CTO (CTRC)', 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': 'University of Colorado Hospital, Anschutz Cancer Pavilion (ACP)', 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': 'University of Colorado Hospital, Anschutz Inpatient Pavilion (AIP)', 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': 'University of Colorado Hospital, Anschutz Outpatient Pavilion (AOP)', 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'facility': 'Emory University Hospital', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'facility': 'Investigational Drug Service', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'facility': 'The Emory Clinic', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'facility': 'Winship Cancer Institute, Emory University', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '78229', 'city': 'San Antonio', 'state': 'Texas', 'country': 'United States', 'facility': 'Mays Cancer Center', 'geoPoint': {'lat': 29.42412, 'lon': -98.49363}}, {'zip': '78229', 'city': 'San Antonio', 'state': 'Texas', 'country': 'United States', 'facility': 'University Health System', 'geoPoint': {'lat': 29.42412, 'lon': -98.49363}}], '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'}}}}