Ignite Creation Date:
2025-12-25 @ 4:03 AM
Ignite Modification Date:
2025-12-26 @ 2:58 AM
Study NCT ID:
NCT04204902
Status:
COMPLETED
Last Update Posted:
2023-11-08
First Post:
2019-12-17
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Bioequivalence of 5 Tablets of 100 mg Versus 2 Tablets of 250 mg TF3 of Tepotinib
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C000707607', 'term': 'tepotinib'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'service@emdgroup.com', 'phone': '+49-6151-72-5200', 'title': 'Communication Center', 'organization': 'Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany'}, 'certainAgreement': {'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Baseline and up to Day 59', 'eventGroups': [{'id': 'EG000', 'title': 'Tepotinib Test Treatment', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in either treatment period 1 or 2.', 'otherNumAtRisk': 18, 'deathsNumAtRisk': 18, 'otherNumAffected': 7, 'seriousNumAtRisk': 18, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Tepotinib Reference Treatment', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in either treatment period 1 or 2.', 'otherNumAtRisk': 18, 'deathsNumAtRisk': 18, 'otherNumAffected': 6, 'seriousNumAtRisk': 18, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Faeces soft', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Gingivitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Burns first degree', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Alanine aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Decreased appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Spinal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Throat irritation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Skin exfoliation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Haematoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}, {'term': 'Hot flush', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 0}], 'organSystem': 'Vascular disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 22.1'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Tepotinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Tepotinib Test Treatment', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in either treatment period 1 or 2.'}, {'id': 'OG001', 'title': 'Tepotinib Reference Treatment', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in either treatment period 1 or 2.'}], 'classes': [{'categories': [{'measurements': [{'value': '15348', 'spread': '28', 'groupId': 'OG000'}, {'value': '16523', 'spread': '37.6', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Ratio of Geometric Least Square Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '91.15', 'ciLowerLimit': '83.21', 'ciUpperLimit': '99.84', 'nonInferiorityType': 'EQUIVALENCE', 'nonInferiorityComment': 'Analysis was performed with Equivalence Acceptance Range for 90 percentage Confidence Interval (CI) as 80.00 percentage - 125.00 percentage'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 'Area under the plasma concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ), calculated using the mixed log linear trapezoidal rule (linear up/log down).', 'unitOfMeasure': 'Hours*nanogram per milliliter (hr*ng/mL)', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': "Pharmacokinetic(PK) Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure."}, {'type': 'PRIMARY', 'title': 'Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Tepotinib Test Treatment', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in either treatment period 1 or 2.'}, {'id': 'OG001', 'title': 'Tepotinib Reference Treatment', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in either treatment period 1 or 2.'}], 'classes': [{'categories': [{'measurements': [{'value': '15958', 'spread': '28.7', 'groupId': 'OG000'}, {'value': '17201', 'spread': '38.5', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Ratio of Geometric Least square Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '90.92', 'ciLowerLimit': '82.99', 'ciUpperLimit': '99.61', 'nonInferiorityType': 'EQUIVALENCE', 'nonInferiorityComment': 'Analysis was performed with Equivalence Acceptance Range for 90 percentage Confidence Interval (CI) as 80.00 percentage - 125.00 percentage'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 'AUC0-inf was calculated as AUC0-t + AUC from time tlast extrapolated to infinity (AUCextra). AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/lambda z, where Clastpred was the predicted plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLOQ) and lambda z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.', 'unitOfMeasure': 'hr*ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': "PK Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure."}, {'type': 'PRIMARY', 'title': 'Maximum Observed Plasma Concentration (Cmax) of Tepotinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Tepotinib Test Treatment', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in either treatment period 1 or 2.'}, {'id': 'OG001', 'title': 'Tepotinib Reference Treatment', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in either treatment period 1 or 2.'}], 'classes': [{'categories': [{'measurements': [{'value': '252', 'spread': '19.1', 'groupId': 'OG000'}, {'value': '240', 'spread': '27.4', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Ratio of Geometric Least Square Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '104.62', 'ciLowerLimit': '95.17', 'ciUpperLimit': '115.00', 'nonInferiorityType': 'EQUIVALENCE', 'nonInferiorityComment': 'Analysis was performed with Equivalence Acceptance Range for 90 percentage Confidence Interval (CI) as 80.00 percentage - 125.00 percentage'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 'Cmax was obtained directly from the concentration versus time curve.', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results.'}, {'type': 'SECONDARY', 'title': 'Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Tepotinib Test Treatment', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in either treatment period 1 or 2.'}, {'id': 'OG001', 'title': 'Tepotinib Reference Treatment', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in either treatment period 1 or 2.'}], 'classes': [{'categories': [{'measurements': [{'value': '12.0', 'groupId': 'OG000', 'lowerLimit': '6', 'upperLimit': '36'}, {'value': '20.1', 'groupId': 'OG001', 'lowerLimit': '6', 'upperLimit': '48'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 'Tmax was obtained directly from the concentration versus time curve.', 'unitOfMeasure': 'Hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results.'}, {'type': 'SECONDARY', 'title': 'Terminal Half-Life (t1/2) of Tepotinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Tepotinib Test Treatment', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in either treatment period 1 or 2.'}, {'id': 'OG001', 'title': 'Tepotinib Reference Treatment', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in either treatment period 1 or 2.'}], 'classes': [{'categories': [{'measurements': [{'value': '33.1', 'spread': '12.6', 'groupId': 'OG000'}, {'value': '32.1', 'spread': '12.3', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 't1/2 was defined as the time taken for the plasma concentration or the amount of drug in the body to be reduced by half.', 'unitOfMeasure': 'Hours', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': "PK Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure."}, {'type': 'SECONDARY', 'title': 'Apparent Volume of Distribution During Terminal Phase (Vz/f) for Tepotinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Tepotinib Test Treatment', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in either treatment period 1 or 2.'}, {'id': 'OG001', 'title': 'Tepotinib Reference Treatment', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in either treatment period 1 or 2.'}], 'classes': [{'categories': [{'measurements': [{'value': '1347', 'spread': '24.3', 'groupId': 'OG000'}, {'value': '1211', 'spread': '33.1', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 'Vz/f is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f during the terminal phase was reported.', 'unitOfMeasure': 'Liters', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': "PK Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure."}, {'type': 'SECONDARY', 'title': 'Apparent Total Body Clearance (CL/f) of Tepotinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Tepotinib Test Treatment', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in either treatment period 1 or 2.'}, {'id': 'OG001', 'title': 'Tepotinib Reference Treatment', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in either treatment period 1 or 2.'}], 'classes': [{'categories': [{'measurements': [{'value': '28.2', 'spread': '28.7', 'groupId': 'OG000'}, {'value': '26.2', 'spread': '38.5', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 'CL/f following oral administration was calculated as Dose/AUC0-inf, where AUC0-inf calculated as AUC0-t + AUC from time tlast extrapolated to infinity (AUCextra). AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/lambda z, where Clastpred was the predicted plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLOQ) and lambda z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.', 'unitOfMeasure': 'Liters per hour', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': "PK Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure."}, {'type': 'SECONDARY', 'title': 'Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Tepotinib Test Treatment', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in either treatment period 1 or 2.'}, {'id': 'OG001', 'title': 'Tepotinib Reference Treatment', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in either treatment period 1 or 2.'}], 'classes': [{'title': 'TEAEs', 'categories': [{'measurements': [{'value': '7', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}]}, {'title': 'Serious TEAEs', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'TEAE leading to Discontinuation', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'TEAEs Leading to Death', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline up to Day 59', 'description': 'An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety Analysis set included all participants who had received at least one dose of planned study intervention and had one subsequent safety assessment.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Tepotinib Test Treatment', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in either treatment period 1 or 2.'}, {'id': 'OG001', 'title': 'Tepotinib Reference Treatment', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in either treatment period 1 or 2.'}], 'classes': [{'title': 'Laboratory parameters', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'ECG', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Vital Signs', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline up to Day 59', 'description': 'Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. Laboratory parameters included hematology, biochemistry, urinalysis, and coagulation. Number of participants with clinically significant change from baseline in vital signs, ECG and laboratory parameters were reported. Clinical Significance was decided by the investigator.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety Analysis set included all participants who had received at least one dose of planned study intervention and had one subsequent safety assessment.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'First Tepotinib Test, Then Tepotinib Reference', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in treatment period 1 followed by a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in treatment period 2. The treatment periods were separated by 21 day washout period.'}, {'id': 'FG001', 'title': 'First Tepotinib Reference, Then Tepotinib Test', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in treatment period 1 followed by a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in treatment period 2. The treatment periods were separated by 21 day washout period.'}], 'periods': [{'title': 'Treatment Period 1 (Day 1)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Washout Period (21 Days)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Treatment Period 2 (Day 22)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '8'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'Overall 42 participants were screened of which 18 participants were randomized in the study.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Entire Study Population', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) or single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in treatment period 1 or 2. The treatment periods were separated by 21 days of washout period.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '43', 'spread': '8.8', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '17', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '18', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '18', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'Safety Analysis Set included all participants who had received at least one dose of planned study intervention and had one subsequent safety assessment.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-09-05', 'size': 1296653, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2023-01-30T07:37', 'hasProtocol': True}, {'date': '2019-11-22', 'size': 22854442, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2023-01-30T07:37', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 18}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-10-17', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-11', 'completionDateStruct': {'date': '2019-12-16', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-01-30', 'studyFirstSubmitDate': '2019-12-17', 'resultsFirstSubmitDate': '2023-01-30', 'studyFirstSubmitQcDate': '2019-12-17', 'lastUpdatePostDateStruct': {'date': '2023-11-08', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-01-30', 'studyFirstPostDateStruct': {'date': '2019-12-19', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2023-11-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-12-16', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Tepotinib', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 'Area under the plasma concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ), calculated using the mixed log linear trapezoidal rule (linear up/log down).'}, {'measure': 'Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 'AUC0-inf was calculated as AUC0-t + AUC from time tlast extrapolated to infinity (AUCextra). AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/lambda z, where Clastpred was the predicted plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLOQ) and lambda z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.'}, {'measure': 'Maximum Observed Plasma Concentration (Cmax) of Tepotinib', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 'Cmax was obtained directly from the concentration versus time curve.'}], 'secondaryOutcomes': [{'measure': 'Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 'Tmax was obtained directly from the concentration versus time curve.'}, {'measure': 'Terminal Half-Life (t1/2) of Tepotinib', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 't1/2 was defined as the time taken for the plasma concentration or the amount of drug in the body to be reduced by half.'}, {'measure': 'Apparent Volume of Distribution During Terminal Phase (Vz/f) for Tepotinib', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 'Vz/f is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f during the terminal phase was reported.'}, {'measure': 'Apparent Total Body Clearance (CL/f) of Tepotinib', 'timeFrame': 'Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose', 'description': 'CL/f following oral administration was calculated as Dose/AUC0-inf, where AUC0-inf calculated as AUC0-t + AUC from time tlast extrapolated to infinity (AUCextra). AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/lambda z, where Clastpred was the predicted plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLOQ) and lambda z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.'}, {'measure': 'Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation', 'timeFrame': 'Baseline up to Day 59', 'description': 'An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs.'}, {'measure': 'Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs', 'timeFrame': 'Baseline up to Day 59', 'description': 'Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. Laboratory parameters included hematology, biochemistry, urinalysis, and coagulation. Number of participants with clinically significant change from baseline in vital signs, ECG and laboratory parameters were reported. Clinical Significance was decided by the investigator.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Tepotinib', 'Bioequivalence', 'Pharmacokinetics'], 'conditions': ['Healthy']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200095_0038', 'label': 'Trial Awareness and Transparency website'}, {'url': 'https://www.merckgroup.com/en/company/contact-us/medinfo-contact-map.html', 'label': 'Medical Information Location Map - Med Info Contacts'}]}, 'descriptionModule': {'briefSummary': 'This study investigated the bioequivalence of the 100 milligrams (mg) and 250 mg dose strengths of tepotinib tablet formulation 3 (TF3) when administered at the same dose under fasted condition.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '55 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Healthy participants of non-child bearing potential\n* Body weight between 50 to 100 kilogram (kg)\n* Body mass index (BMI) between 18.5 and 29.9 kilogram per meter square (kg/m\\^2)\n* Other protocol defined inclusion criteria could apply\n\nExclusion Criteria:\n\n* Participation in a clinical study within 60 days prior to first drug administration\n* Whole blood donation or loss of greater than 450 milliliter (mL) within 60 days prior to first drug administration\n* Any surgical or medical condition, or any other significant disease that could interfere with the study objectives, conduct, or evaluation\n* Other protocol defined exclusion criteria could apply'}, 'identificationModule': {'nctId': 'NCT04204902', 'briefTitle': 'Bioequivalence of 5 Tablets of 100 mg Versus 2 Tablets of 250 mg TF3 of Tepotinib', 'organization': {'class': 'INDUSTRY', 'fullName': 'Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany'}, 'officialTitle': 'An Open-label, Single-dose, Randomized, 2-period, 2-sequence Cross-over, Single-center Phase I Trial in Healthy Subjects to Assess the Bioequivalence of Tepotinib TF3 Administered as 5 Tablets of 100 mg Versus 2 Tablets of 250 mg Dose Strength', 'orgStudyIdInfo': {'id': 'MS200095_0038'}, 'secondaryIdInfos': [{'id': '2019-003578-13', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Test Treatment then Reference Treatment', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in treatment period 1 followed by a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in treatment period 2. The treatment periods were separated by 21 day washout period.', 'interventionNames': ['Drug: Tepotinib 100 mg', 'Drug: Tepotinib 250 mg']}, {'type': 'EXPERIMENTAL', 'label': 'Reference Treatment then Test Treatment', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in treatment period 1 followed by a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in treatment period 2. The treatment periods were separated by 21 day washout period.', 'interventionNames': ['Drug: Tepotinib 100 mg', 'Drug: Tepotinib 250 mg']}], 'interventions': [{'name': 'Tepotinib 100 mg', 'type': 'DRUG', 'description': 'Participants received a single oral dose of test treatment of tepotinib TF3 (5 \\* 100 mg) in either treatment period 1 or 2.', 'armGroupLabels': ['Reference Treatment then Test Treatment', 'Test Treatment then Reference Treatment']}, {'name': 'Tepotinib 250 mg', 'type': 'DRUG', 'description': 'Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \\* 250 mg) in either treatment period 1 or 2.', 'armGroupLabels': ['Reference Treatment then Test Treatment', 'Test Treatment then Reference Treatment']}]}, 'contactsLocationsModule': {'locations': [{'zip': '89231', 'city': 'Neu-Ulm', 'country': 'Germany', 'facility': 'Nuvisan GmbH', 'geoPoint': {'lat': 48.39279, 'lon': 10.01112}}], 'overallOfficials': [{'name': 'Medical Responsible', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}