Ignite Creation Date:
2025-12-25 @ 3:09 AM
Ignite Modification Date:
2025-12-30 @ 9:48 PM
Study NCT ID:
NCT05225805
Status:
COMPLETED
Last Update Posted:
2024-06-17
First Post:
2022-01-07
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Study to Assess the Safety and PK of Oral and IV Xenleta in Adults With Cystic Fibrosis
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003550', 'term': 'Cystic Fibrosis'}], 'ancestors': [{'id': 'D010182', 'term': 'Pancreatic Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D007232', 'term': 'Infant, Newborn, Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000591018', 'term': 'lefamulin'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'christine.guico-pabia@nabriva.com', 'phone': '610-981-2874', 'title': 'Christine Guico-Pabia, MD, MBA, MPH', 'organization': 'Nabriva Therapeutics US, Inc.'}, 'certainAgreement': {'restrictionType': 'LTE60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Up-to Follow-up (4 to 7 days after the final dose).', 'description': 'Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.', 'eventGroups': [{'id': 'EG000', 'title': 'Lefamulin Oral Treatment', 'description': 'Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.', 'otherNumAtRisk': 13, 'deathsNumAtRisk': 13, 'otherNumAffected': 4, 'seriousNumAtRisk': 13, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Lefamulin IV Treatment', 'description': 'Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.', 'otherNumAtRisk': 13, 'deathsNumAtRisk': 13, 'otherNumAffected': 4, 'seriousNumAtRisk': 13, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Total', 'description': 'Lefamulin oral treatment + Lefamulin IV treatment\n\nLefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.\n\nLefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.', 'otherNumAtRisk': 13, 'deathsNumAtRisk': 13, 'otherNumAffected': 6, 'seriousNumAtRisk': 13, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (25.0)'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (25.0)'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (25.0)'}, {'term': 'Infusion site erythema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (25.0)'}, {'term': 'Infusion site pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (25.0)'}, {'term': 'Cystic fibrosis gastrointestinal disease', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'Congenital, familial and genetic disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (25.0)'}, {'term': 'Tooth fracture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (25.0)'}, {'term': 'Presyncope', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (25.0)'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'The Median for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter Tmax in Cystic Fibrosis (CF) Patients.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Lefamulin Oral Treatment', 'description': 'Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.'}, {'id': 'OG001', 'title': 'Lefamulin IV Treatment', 'description': 'Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.'}], 'classes': [{'title': 'Lefamulin', 'categories': [{'measurements': [{'value': '2.00', 'groupId': 'OG000', 'lowerLimit': '0.983', 'upperLimit': '3.900'}, {'value': '0.583', 'groupId': 'OG001', 'lowerLimit': '0.500', 'upperLimit': '1.717'}]}]}, {'title': 'Lefamulin metabolite BC-8041', 'categories': [{'measurements': [{'value': '1.517', 'groupId': 'OG000', 'lowerLimit': '1.017', 'upperLimit': '4.017'}, {'value': '1.500', 'groupId': 'OG001', 'lowerLimit': '0.933', 'upperLimit': '1.817'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose', 'description': 'Appropriate non-compartmental techniques were used to obtain estimates for the PK parameter Tmax in plasma for lefamulin and its metabolite BC-8041.\n\nTime to reach maximum plasma concentration of lefamulin following drug administration (Tmax)\n\nTmax will be determined by direct inspection of the concentration versus time data by WinNonlin.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic (PK) Population: All 13 adult subjects completed both periods of the study. Plasma samples from 13 subjects were analyzed for lefamulin and BC-8041.'}, {'type': 'PRIMARY', 'title': 'The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter Cmax in CF Patients.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Lefamulin Oral Treatment', 'description': 'Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.'}, {'id': 'OG001', 'title': 'Lefamulin IV Treatment', 'description': 'Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.'}], 'classes': [{'title': 'Lefamulin', 'categories': [{'measurements': [{'value': '1.314', 'spread': '0.308', 'groupId': 'OG000'}, {'value': '1.924', 'spread': '0.417', 'groupId': 'OG001'}]}]}, {'title': 'Lefamulin Metabolite BC-8041', 'categories': [{'measurements': [{'value': '0.351', 'spread': '0.417', 'groupId': 'OG000'}, {'value': '0.030', 'spread': '0.470', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose', 'description': 'Appropriate non-compartmental techniques will be used to obtain estimates for the PK parameter Cmax in plasma for lefamulin and its metabolite BC-8041.\n\nMaximum observed plasma concentration (Cmax)\n\nCmax was determined by direct inspection of the concentration versus time data by WinNonlin.', 'unitOfMeasure': 'mg/L', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic (PK) Population: All 13 adult subjects completed both periods of the study. Plasma samples from 13 subjects were analyzed for lefamulin and BC-8041.'}, {'type': 'PRIMARY', 'title': 'The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter AUC(0-last) in CF Patients.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Oral Treatment', 'description': 'Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.'}, {'id': 'OG001', 'title': 'IV Treatment', 'description': 'Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.'}], 'classes': [{'title': 'Lefamulin', 'categories': [{'measurements': [{'value': '6.881', 'spread': '0.380', 'groupId': 'OG000'}, {'value': '6.220', 'spread': '0.286', 'groupId': 'OG001'}]}]}, {'title': 'Lefamulin Metabolite BC-8041', 'categories': [{'measurements': [{'value': '1.990', 'spread': '0.442', 'groupId': 'OG000'}, {'value': '0.232', 'spread': '0.536', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose', 'description': 'Appropriate non-compartmental techniques will be used to obtain estimates for the PK parameter (AUC0-last) in plasma for lefamulin and its metabolite BC-8041.\n\nAUC calculations will be performed using the linear/log trapezoidal rule. AUC0-last will be calculated between t0hr and the last measurable concentration.\n\nArea under the drug concentration curve from time zero (0 h) to 24 h (AUC0-last)', 'unitOfMeasure': 'mg·h/L', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic (PK) Population: All 13 adult subjects completed both periods of the study. Plasma samples from 13 subjects were analyzed for lefamulin and BC-8041.'}, {'type': 'PRIMARY', 'title': 'The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter AUC(0-inf) in CF Patients.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Lefamulin Oral Treatment', 'description': 'Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.'}, {'id': 'OG001', 'title': 'Lefamulin IV Treatment', 'description': 'Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.'}], 'classes': [{'title': 'Lefamulin', 'categories': [{'measurements': [{'value': '7.277', 'spread': '0.384', 'groupId': 'OG000'}, {'value': '6.568', 'spread': '0.286', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite BC-8041', 'categories': [{'measurements': [{'value': '2.095', 'spread': '0.448', 'groupId': 'OG000'}, {'value': '0.272', 'spread': '0.517', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose', 'description': 'Appropriate non-compartmental techniques will be used to obtain estimates for PK parameter AUC(0-inf) in plasma for lefamulin and its metabolite BC-8041.\n\nAUC calculations will be performed using the linear/log trapezoidal rule. AUC(0-inf) will be will be calculated between t0hr and infinity.\n\nArea under the drug concentration curve from time zero (0 h) to infinity (AUC(0-inf)', 'unitOfMeasure': 'mg·h/L', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic (PK) Population: All 13 adult subjects completed both periods of the study. Plasma samples from 13 subjects were analyzed for lefamulin and BC-8041.'}, {'type': 'PRIMARY', 'title': 'The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter t1/2 in CF Patients.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Oral Treatment', 'description': 'Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.'}, {'id': 'OG001', 'title': 'IV Treatment', 'description': 'Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.'}], 'classes': [{'title': 'Lefamulin', 'categories': [{'measurements': [{'value': '6.422', 'spread': '0.182', 'groupId': 'OG000'}, {'value': '6.297', 'spread': '0.188', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite BC-8041', 'categories': [{'measurements': [{'value': '5.796', 'spread': '0.175', 'groupId': 'OG000'}, {'value': '8.128', 'spread': '0.176', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose', 'description': 'Appropriate non-compartmental techniques will be used to obtain estimates for thr PK parameter t1/2 in plasma for lefamulin and its metabolite BC-8041.\n\nApparent elimination half-life calculated as ln(2)/ke (t½)', 'unitOfMeasure': 'hours', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic (PK) Population: All 13 adult subjects completed both periods of the study. Plasma samples from 13 subjects were analyzed for lefamulin and BC-8041.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Group A (IV-Oral)', 'description': 'Group A will receive single dose of lefamulin 150 mg IV infusion in 250 mL citrate buffered saline over 1 hour followed by lefamulin 600-mg immediate-release (IR) tablet orally in the fasted state.\n\nLefamulin: Antibiotic'}, {'id': 'FG001', 'title': 'Group B (Oral-IV)', 'description': 'Group B will receive single dose of lefamulin 600 mg immediate-release (IR) tablet orally in the fasted state followed by single dose of lefamulin 150 mg IV infusion in 250 mL citrate buffered saline over 1 hour.\n\nLefamulin: Antibiotic'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '7'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '7'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'This study was conducted at multiple investigative sites in United States.', 'preAssignmentDetails': 'A total of 13 subjects (4 females, 9 males) was enrolled in the study and treated in the study NAB-BC-3781-1014. One subject failed screening.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Group A (IV-Oral)', 'description': 'Group A will receive single dose of lefamulin 150 mg IV infusion in 250 mL citrate buffered saline over 1 hour followed by lefamulin 600-mg immediate-release (IR) tablet orally in the fasted state.\n\nLefamulin: Antibiotic'}, {'id': 'BG001', 'title': 'Group B (Oral-IV)', 'description': 'Group B will receive single dose of lefamulin 600 mg immediate-release (IR) tablet orally in the fasted state followed by single dose of lefamulin 150 mg IV infusion in 250 mL citrate buffered saline over 1 hour.\n\nLefamulin: Antibiotic'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '27.0', 'spread': '11.14', 'groupId': 'BG000'}, {'value': '31.1', 'spread': '9.01', 'groupId': 'BG001'}, {'value': '29.2', 'spread': '9.84', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'Safety population: All 13 adult subjects received at least 1 dose of IMP and were included in the safety population.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-11-02', 'size': 541075, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2023-12-22T04:50', 'hasProtocol': True}, {'date': '2022-09-16', 'size': 779962, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2023-12-22T04:51', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'Open-label, Crossover Study'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 13}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2022-03-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-01', 'completionDateStruct': {'date': '2023-01-13', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-12-28', 'studyFirstSubmitDate': '2022-01-07', 'resultsFirstSubmitDate': '2023-12-28', 'studyFirstSubmitQcDate': '2022-02-02', 'lastUpdatePostDateStruct': {'date': '2024-06-17', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-12-28', 'studyFirstPostDateStruct': {'date': '2022-02-07', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2024-06-17', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-09-20', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'The Median for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter Tmax in Cystic Fibrosis (CF) Patients.', 'timeFrame': 'Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose', 'description': 'Appropriate non-compartmental techniques were used to obtain estimates for the PK parameter Tmax in plasma for lefamulin and its metabolite BC-8041.\n\nTime to reach maximum plasma concentration of lefamulin following drug administration (Tmax)\n\nTmax will be determined by direct inspection of the concentration versus time data by WinNonlin.'}, {'measure': 'The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter Cmax in CF Patients.', 'timeFrame': 'Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose', 'description': 'Appropriate non-compartmental techniques will be used to obtain estimates for the PK parameter Cmax in plasma for lefamulin and its metabolite BC-8041.\n\nMaximum observed plasma concentration (Cmax)\n\nCmax was determined by direct inspection of the concentration versus time data by WinNonlin.'}, {'measure': 'The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter AUC(0-last) in CF Patients.', 'timeFrame': 'Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose', 'description': 'Appropriate non-compartmental techniques will be used to obtain estimates for the PK parameter (AUC0-last) in plasma for lefamulin and its metabolite BC-8041.\n\nAUC calculations will be performed using the linear/log trapezoidal rule. AUC0-last will be calculated between t0hr and the last measurable concentration.\n\nArea under the drug concentration curve from time zero (0 h) to 24 h (AUC0-last)'}, {'measure': 'The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter AUC(0-inf) in CF Patients.', 'timeFrame': 'Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose', 'description': 'Appropriate non-compartmental techniques will be used to obtain estimates for PK parameter AUC(0-inf) in plasma for lefamulin and its metabolite BC-8041.\n\nAUC calculations will be performed using the linear/log trapezoidal rule. AUC(0-inf) will be will be calculated between t0hr and infinity.\n\nArea under the drug concentration curve from time zero (0 h) to infinity (AUC(0-inf)'}, {'measure': 'The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter t1/2 in CF Patients.', 'timeFrame': 'Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose', 'description': 'Appropriate non-compartmental techniques will be used to obtain estimates for thr PK parameter t1/2 in plasma for lefamulin and its metabolite BC-8041.\n\nApparent elimination half-life calculated as ln(2)/ke (t½)'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Cystic Fibrosis']}, 'referencesModule': {'references': [{'pmid': '38195348', 'type': 'DERIVED', 'citation': 'Sawicki GS, Wicha WW, Hiley TS, Close NC, Gelone SP, Guico-Pabia CJ. Safety and Pharmacokinetics Following Oral or Intravenous Lefamulin in Adults With Cystic Fibrosis. Clin Ther. 2024 Feb;46(2):96-103. doi: 10.1016/j.clinthera.2023.12.002. Epub 2024 Jan 8.'}]}, 'descriptionModule': {'briefSummary': 'This study is intended to assess the pharmacokinetic (PK) and safety of a single dose of IV and oral formulations of lefamulin in adults with cystic fibrosis (CF).', 'detailedDescription': 'Staphylococcus aureus is one of the most common causative pathogens associated with exacerbations of CF. Current treatment guidelines for the management of exacerbations of CF caused by S. aureus recommend the use of unapproved antibacterial agents. Further, many of the recommended treatments can only be administered via the IV route and/or have limitations due to safety and tolerability. Lefamulin is a novel, first-in-class, IV and oral pleuromutilin antimicrobial agent that has been demonstrated to be highly potent against S. aureus, including Methicillin-resistant Staphylococcus aureus (MRSA) and strains obtained from patients with CF. Cystic fibrosis patients have altered drug distribution and elimination kinetics for many antimicrobials relative to patients without CF. While the advent of Cystic fibrosis transmembrane conductance regulator (protein) (CFTR) modulators has resulted in improved lung function and had a positive impact on the quality of life of CF patients, limited data have been published describing the impact of the concomitant use of CFTR modulators and commonly used antibacterial agents.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Signed informed consent.\n2. Adult patients, ≥ 18 years of age.\n3. Genetic confirmation of CF diagnosis by a report from a genetic test, such as "F508 deletion detected."\n4. Weight \\> 40 kgs.\n5. Forced expiration volume (FEV)1 \\> 40% predicted, as measured during the most recent evaluation.\n6. Mentally and physically able to participate in the study as determined by the Investigator, ie, clinically stable with no significant changes in health status within 28 days prior to, and including, Day 1.\n7. Vital signs within the following ranges:\n\n 1. Tympanic temperature, \\< 38°C\n 2. Systolic blood pressure, 90 to 160 mmHg\n 3. Diastolic blood pressure, 50 to 90 mmHg\n 4. Heart rate \\< 100 beats per minute at rest\n 5. Respiration rate 12 to 20 breaths per minute\n 6. Oxygen saturation to be documented. No selection criteria; supplemental oxygen use is acceptable.\n8. Negative beta-human chorionic gonadotropin (β-hCG) urine or serum pregnancy test for females of childbearing potential.\n9. Willing to commit to acceptable methods of contraception as defined in the protocol.\n\nExclusion Criteria:\n\n1. Known history of chronic liver or biliary disease, Gilbert\'s syndrome, or any of the following at Screening: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \\> 2 x upper limit of normal (ULN), total bilirubin \\> 1.5 x ULN.\n2. Prolonged baseline corrected QT interval corrected according to Fridericia (QTcF) defined as \\> 440 ms (females) and \\> 430 ms (males).\n3. Family history or presence of prolonged QTc syndrome, Torsades de Pointes, or known conduction defects (eg, bundle branch block, atrioventricular block).\n4. Use of Orkambi® (lumacaftor/ivacaftor) within 28 days prior to Day 1.\n5. Use of cytochrome P450 (CYP)3A substrates that prolong the QT interval within 24 hours prior to Day 1.\n6. Use of strong and moderate Cytochrome P450 (CYP3A) inducers or P-glycoprotein (P-gp) inducers within 28 days prior to Day 1.\n7. Use of strong inhibitors of CYP3A4 within 24 hours prior to Day 1.\n8. Serum potassium level below the normal reference range at Screening.\n9. Known allergy to pleuromutilin class of antibiotic or any of the excipients of the lefamulin formulations.\n10. Consumption of grapefruit, grapefruit juice, grapefruit products, pomelo, or Seville oranges within 24 hours before Day 1.\n11. Use of vaporized nicotine or cannabidiol products, smoking (regularly or intermittently) more than 5 cigarettes (or equivalent) per day, or any use of tobacco other than in cigarettes or cigars within 28 days of Day 1.\n12. Positive blood test for hepatitis C, human immunodeficiency virus (HIV), or hepatitis B antigen or core antibody (indicating active infection).\n13. Positive test for drugs of abuse or alcohol at Screening or Day 1 that cannot be satisfactorily supported by medical history.\n14. Use of an investigational product within the 30 days prior to Day 1 (3 months prior to Day 1 if the study drug was a new chemical entity).\n15. Difficulty swallowing tablets.\n16. Females who are pregnant or breastfeeding.\n17. Does not have suitable venous access for multiple venipuncture or cannulation.\n18. Any medical, psychological, cognitive, social, or legal conditions that, in the opinion of the Investigator, would interfere with the patient\'s ability to give an informed consent and/or participate fully in the study.\n19. Any other reason, in the opinion of the Investigator, the patient is unsuitable to participate.'}, 'identificationModule': {'nctId': 'NCT05225805', 'briefTitle': 'Study to Assess the Safety and PK of Oral and IV Xenleta in Adults With Cystic Fibrosis', 'organization': {'class': 'INDUSTRY', 'fullName': 'Nabriva Therapeutics AG'}, 'officialTitle': 'A Phase 1, Open-Label, Randomized, Crossover Study to Assess the Safety and Pharmacokinetics Following Single Doses of Oral and Intravenous Xenleta (Lefamulin) in Adult Patients With Cystic Fibrosis', 'orgStudyIdInfo': {'id': 'NAB-BC-3781-1014'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Group A', 'description': 'Group A will receive one dose of 150 mg lefamulin IV followed by one dose of 600 mg lefamulin oral', 'interventionNames': ['Drug: Lefamulin']}, {'type': 'EXPERIMENTAL', 'label': 'Group B', 'description': 'Group B will receive one dose of 600 mg lefamulin oral followed by one dose of 150 mg lefamulin IV', 'interventionNames': ['Drug: Lefamulin']}], 'interventions': [{'name': 'Lefamulin', 'type': 'DRUG', 'otherNames': ['BC-3781'], 'description': 'Antibiotic', 'armGroupLabels': ['Group A', 'Group B']}]}, 'contactsLocationsModule': {'locations': [{'zip': '66160', 'city': 'Kansas City', 'state': 'Kansas', 'country': 'United States', 'facility': 'University of Kansas School of Medicine', 'geoPoint': {'lat': 39.11417, 'lon': -94.62746}}, {'zip': '02115', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': "Boston Children's Hospital", 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '10595', 'city': 'Valhalla', 'state': 'New York', 'country': 'United States', 'facility': 'New York Medical College', 'geoPoint': {'lat': 41.07482, 'lon': -73.77513}}, {'zip': '44106', 'city': 'Cleveland', 'state': 'Ohio', 'country': 'United States', 'facility': 'University Hospitals Cleveland Medical Center', 'geoPoint': {'lat': 41.4995, 'lon': -81.69541}}, {'zip': '17033', 'city': 'Hershey', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'Penn State University College of Medicine', 'geoPoint': {'lat': 40.28592, 'lon': -76.65025}}, {'zip': '84112', 'city': 'Salt Lake City', 'state': 'Utah', 'country': 'United States', 'facility': 'University of Utah', 'geoPoint': {'lat': 40.76078, 'lon': -111.89105}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Nabriva Therapeutics AG', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}