Ignite Creation Date:
2025-12-25 @ 12:59 AM
Ignite Modification Date:
2025-12-25 @ 11:13 PM
Study NCT ID:
NCT04419493
Status:
COMPLETED
Last Update Posted:
2023-04-26
First Post:
2020-06-04
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
A Study in Healthy Men to Compare 2 Different Formulations of Alteplase
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D010959', 'term': 'Tissue Plasminogen Activator'}, {'id': 'D006493', 'term': 'Heparin'}], 'ancestors': [{'id': 'D012697', 'term': 'Serine Endopeptidases'}, {'id': 'D010450', 'term': 'Endopeptidases'}, {'id': 'D010447', 'term': 'Peptide Hydrolases'}, {'id': 'D006867', 'term': 'Hydrolases'}, {'id': 'D004798', 'term': 'Enzymes'}, {'id': 'D045762', 'term': 'Enzymes and Coenzymes'}, {'id': 'D057057', 'term': 'Serine Proteases'}, {'id': 'D010960', 'term': 'Plasminogen Activators'}, {'id': 'D001779', 'term': 'Blood Coagulation Factors'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D001685', 'term': 'Biological Factors'}, {'id': 'D006025', 'term': 'Glycosaminoglycans'}, {'id': 'D011134', 'term': 'Polysaccharides'}, {'id': 'D002241', 'term': 'Carbohydrates'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'clintriage.rdg@boehringer-ingelheim.com', 'phone': '1-800-243-0127', 'title': 'Boehringer Ingelheim, Call Center', 'organization': 'Boehringer Ingelheim'}, 'certainAgreement': {'piSponsorEmployee': True}, 'limitationsAndCaveats': {'description': 'For study Part A three subjects underwent only one treatment period, thereafter the trial was put on-hold. Trial Part B was performed as planned. There were no important protocol deviations (IPDs). Each entered subject met all of the inclusion criteria and none of the exclusion criteria.'}}, 'adverseEventsModule': {'timeFrame': 'Up to 22 days after the last administration of alteplase.', 'description': 'Treated set - part A (TS-A) and Treated set - part B (TS-B): The treated sets includes all subjects who were randomized and treated with at least one dose of study drug.', 'eventGroups': [{'id': 'EG000', 'title': 'Part A: Alteplase, TPA-02', 'description': 'Participants were administered during trial Part A a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 minutes (min) infusion.', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 1, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Part B: Alteplase, TPA-02', 'description': 'Participants were administered during trial Part B a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 minutes (min) infusion. 5 min prior to the infusion of alteplase, TPA-02, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.', 'otherNumAtRisk': 18, 'deathsNumAtRisk': 18, 'otherNumAffected': 7, 'seriousNumAtRisk': 18, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Part A: Alteplase, TPA-05', 'description': 'Participants were administered during trial Part A a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 minutes (min) infusion.', 'otherNumAtRisk': 11, 'deathsNumAtRisk': 11, 'otherNumAffected': 4, 'seriousNumAtRisk': 11, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG003', 'title': 'Part B: Alteplase, TPA-05', 'description': 'Participants were administered during trial Part B a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 minutes (min) infusion. 5 min prior to the infusion of alteplase, TPA-05, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.', 'otherNumAtRisk': 17, 'deathsNumAtRisk': 17, 'otherNumAffected': 6, 'seriousNumAtRisk': 17, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Catheter site paraesthesia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Catheter site swelling', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Haematoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Catheter site haematoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Catheter site pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Infusion site pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Vessel puncture site haematoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Muscle discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Paraesthesia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Hypotension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 0}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Subcutaneous haematoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 0}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Device occlusion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 18, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 11, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 17, 'numAffected': 1}], 'organSystem': 'Product Issues', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Part A: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Time Interval From 0 up to the Last Quantifiable Data Point (AUC0-tz)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Part A: Alteplase, TPA -02', 'description': 'Participants were administered during trial Part A a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 minutes (min) infusion.'}, {'id': 'OG001', 'title': 'Part A: Alteplase, TPA-05', 'description': 'Participants were administered during trial Part B a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 minutes (min) infusion.'}], 'timeFrame': 'Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.', 'description': 'The area under the concentration-time curve of alteplase in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic parameter analysis set - part A (PKS-A): Includes all subjects in the treated set - part A (TS-A) who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol violation to the evaluation of PK or due to PK non-evaluability. PK data for Part A were not used for the final assessment of bioequivalence according to protocol amendment after obtaining unreliable PK results.'}, {'type': 'PRIMARY', 'title': 'Part B: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Time Interval From 0 up to the Last Quantifiable Data Point (AUC0-tz)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}, {'value': '16', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Part B: Alteplase, TPA -02', 'description': 'Participants were administered during trial Part B a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 minutes (min) infusion. 5 min prior to the infusion of alteplase, TPA-02, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.'}, {'id': 'OG001', 'title': 'Part B: Alteplase, TPA-05', 'description': 'Participants were administered during trial Part B a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 minutes (min) infusion. 5 min prior to the infusion of alteplase, TPA-05, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.'}], 'classes': [{'categories': [{'measurements': [{'value': '369.21', 'spread': 'NA', 'comment': 'The standard error is actually adjusted standard error and is equal to 1.03.', 'groupId': 'OG000'}, {'value': '377.35', 'spread': 'NA', 'comment': 'The standard error is actually adjusted standard error and is equal to 1.03.', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric Least Squares Mean ratio (%)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '92.83', 'paramValue': '102.20', 'ciLowerLimit': '94.87', 'ciUpperLimit': '110.10', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '10.8', 'estimateComment': 'Geometric Least Squares Mean ratio is: Alteplase, TPA-02/Alteplase, TPA-05. Standard Error of the mean is actually the intra-individual geometric coefficient variation.', 'groupDescription': 'The null hypothesis was that the ratio of expected geometric least squares means Alteplase, TPA-02 vs. Alteplase, TPA-05 is less than 80.00% or more than 125.00%.\n\nThe statistical model used for the analysis of this endpoints was an analysis of variance (ANOVA) model on the logarithmic scale.\n\nThis model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. All effects were considered as fixed.', 'nonInferiorityType': 'EQUIVALENCE', 'nonInferiorityComment': 'Bioequivalence was concluded, if the confidence interval (CI) for the comparison of geometric least squares means ratio was included in the pre-defined equivalence range of 80.00% to 125.00%'}], 'paramType': 'GEOMETRIC_LEAST_SQUARES_MEAN', 'timeFrame': 'Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.', 'description': 'The area under the concentration-time curve of Alteplase in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.', 'unitOfMeasure': 'hour * nanogram / milliliter (h*ng/mL)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic parameter analysis set - part B(PKS-B): This set includes all subjects in the treated set - part B (TS-B) who provide at least one Pharmacokinetic (PK) endpoint that was defined as primary or secondary and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.'}, {'type': 'PRIMARY', 'title': 'Part A: Maximum Measured Concentration of Alteplase in Plasma (Cmax)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Part A: Alteplase, TPA -02', 'description': 'Participants were administered during trial Part A a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 minutes (min) infusion.'}, {'id': 'OG001', 'title': 'Part A: Alteplase, TPA-05', 'description': 'Participants were administered during trial Part A a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 minutes (min) infusion.'}], 'timeFrame': 'Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.', 'description': 'Maximum measured concentration of alteplase in plasma is reported.', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic parameter analysis set - part A (PKS-A): Includes all subjects in the treated set - part A (TS-A) who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol violation to the evaluation of PK or due to PK non-evaluability. PK data for Part A were not used for the final assessment of bioequivalence according to protocol amendment after obtaining unreliable PK results.'}, {'type': 'PRIMARY', 'title': 'Part B: Maximum Measured Concentration of Alteplase in Plasma (Cmax)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}, {'value': '16', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Part B: Alteplase, TPA -02', 'description': 'Participants were administered during trial Part B a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 minutes (min) infusion. 5 min prior to the infusion of alteplase, TPA-02, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.'}, {'id': 'OG001', 'title': 'Part B: Alteplase, TPA-05', 'description': 'Participants were administered during trial Part B a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 minutes (min) infusion. 5 min prior to the infusion of alteplase, TPA-05, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.'}], 'classes': [{'categories': [{'measurements': [{'value': '738.35', 'spread': 'NA', 'comment': 'The standard error is actually adjusted standard error and is equal to 1.02.', 'groupId': 'OG000'}, {'value': '781.24', 'spread': 'NA', 'comment': 'The standard error is actually adjusted standard error and is equal to 1.02.', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric Least Squares Mean ratio (%)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '92.83', 'paramValue': '105.81', 'ciLowerLimit': '99.18', 'ciUpperLimit': '112.88', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '9.3', 'estimateComment': 'Geometric Least Squares Mean ratio is: Alteplase, TPA-02/Alteplase, TPA-05. Standard Error of the mean is actually the intra-individual geometric coefficient variation.', 'groupDescription': 'The null hypothesis was that the ratio of expected geometric least squares means Alteplase, TPA-02 vs. Alteplase, TPA-05 is less than 80.00% or more than 125.00%.\n\nThe statistical model used for the analysis of this endpoints was an analysis of variance (ANOVA) model on the logarithmic scale.\n\nThis model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. All effects were considered as fixed.', 'nonInferiorityType': 'EQUIVALENCE', 'nonInferiorityComment': 'Bioequivalence was concluded, if the confidence interval (CI) for the comparison of geometric least squares means ratio was included in the pre-defined equivalence range of 80.00% to 125.00%'}], 'paramType': 'GEOMETRIC_LEAST_SQUARES_MEAN', 'timeFrame': 'Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.', 'description': 'Maximum measured concentration of Alteplase in plasma (Cmax) is reported.', 'unitOfMeasure': 'nanogram / milliliter (ng/mL)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic parameter analysis set - part B(PKS-B): This set includes all subjects in the treated set - part B (TS-B) who provide at least one Pharmacokinetic (PK) endpoint that was defined as primary or secondary and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.'}, {'type': 'SECONDARY', 'title': 'Part A: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Part A: Alteplase, TPA -02', 'description': 'Participants were administered during trial Part A a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 minutes (min) infusion.'}, {'id': 'OG001', 'title': 'Part A: Alteplase, TPA-05', 'description': 'Participants were administered during trial Part A a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 minutes (min) infusion.'}], 'timeFrame': 'Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.', 'description': 'Area under the concentration-time curve of alteplase in plasma over interval from 0 extrapolated to infinity is reported.', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic parameter analysis set - part A (PKS-A): Includes all subjects in the treated set - part A (TS-A) who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol violation to the evaluation of PK or due to PK non-evaluability. PK data for Part A were not used for the final assessment of bioequivalence according to protocol amendment after obtaining unreliable PK results.'}, {'type': 'SECONDARY', 'title': 'Part B: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Interval From 0 Extrapolated to Infinity (AUC0-∞)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}, {'value': '16', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Part B: Alteplase, TPA -02', 'description': 'Participants were administered during trial Part B a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 minutes (min) infusion. 5 min prior to the infusion of alteplase, TPA-02, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.'}, {'id': 'OG001', 'title': 'Part B: Alteplase, TPA-05', 'description': 'Participants were administered during trial Part B a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 minutes (min) infusion. 5 min prior to the infusion of alteplase, TPA-05, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.'}], 'classes': [{'categories': [{'measurements': [{'value': '371.85', 'spread': 'NA', 'comment': 'The standard error is actually adjusted standard error and is equal to 1.03.', 'groupId': 'OG000'}, {'value': '379.90', 'spread': 'NA', 'comment': 'The standard error is actually adjusted standard error and is equal to 1.03.', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric Least Squares Mean ratio (%)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '92.83', 'paramValue': '102.17', 'ciLowerLimit': '94.79', 'ciUpperLimit': '110.12', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '10.8', 'estimateComment': 'Geometric Least Squares Mean ratio is: Alteplase, TPA-02/Alteplase, TPA-05. Standard Error of the mean is actually the intra-individual geometric coefficient variation.', 'groupDescription': 'The null hypothesis was that the ratio of expected geometric least squares means Alteplase, TPA-02 vs. Alteplase, TPA-05 is less than 80.00% or more than 125.00%.\n\nThe statistical model used for the analysis of this endpoints was an analysis of variance (ANOVA) model on the logarithmic scale.\n\nThis model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. All effects were considered as fixed.', 'nonInferiorityType': 'EQUIVALENCE', 'nonInferiorityComment': 'Bioequivalence was concluded, if the confidence interval (CI) for the comparison of geometric least squares means ratio was included in the pre-defined equivalence range of 80.00% to 125.00% .'}], 'paramType': 'GEOMETRIC_LEAST_SQUARES_MEAN', 'timeFrame': 'Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.', 'description': 'Area under the concentration-time curve of alteplase in plasma over the interval from 0 extrapolated to infinity is reported.', 'unitOfMeasure': 'hour*nanogram/milliliter (h*ng/mL)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic parameter analysis set - part B(PKS-B): This set includes all subjects in the treated set - part B (TS-B) who provide at least one Pharmacokinetic (PK) endpoint that was defined as primary or secondary and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Part A: Alteplase, TPA-02 Then Alteplase, TPA-05', 'description': 'Participants were administered on Day 1 of Period 1 a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 minutes (min) infusion.\n\nOn Day 1 of Period 2 participants were administered a single dose of 0.2 mg/kg body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 min infusion.\n\nThe 2 treatment periods were separated by a washout period of at least 24 hours (h).'}, {'id': 'FG001', 'title': 'Part A: Alteplase, TPA-05 Then Alteplase, TPA-02', 'description': 'Participants were administered on Day 1 of Period 1 a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 minutes (min) infusion.\n\nOn Day 1 of Period 2 participants were administered a single dose of 0.2 mg/kg body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 min infusion.\n\nThe 2 treatment periods were separated by a washout period of at least 24 hours (h).'}, {'id': 'FG002', 'title': 'Part B: Alteplase, TPA-02 Then Alteplase, TPA-05', 'description': 'Participants were administered on Day 1 of Period 1 a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 minutes (min) infusion. 5 min prior to the infusion of alteplase, TPA-02, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.\n\nOn Day 1 of Period 2 participants were administered a single dose of 0.2 mg/kg body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 min infusion. 5 min prior to the infusion of alteplase, TPA-05, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.\n\nThe 2 treatment periods were separated by a washout period of at least 24 hours (h).'}, {'id': 'FG003', 'title': 'Part B: Alteplase, TPA-05 Then Alteplase, TPA-02', 'description': 'Participants were administered on Day 1 of Period 1 a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 minutes (min) infusion. 5 min prior to the infusion of alteplase, TPA-05, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.\n\nOn Day 1 of Period 2 participants were administered a single dose of 0.2 mg/kg body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 min infusion. 5 min prior to the infusion of alteplase, TPA-02, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.\n\nThe 2 treatment periods were separated by a washout period of at least 24 hours (h).'}], 'periods': [{'title': 'Period 1', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}, {'groupId': 'FG002', 'numSubjects': '9'}, {'groupId': 'FG003', 'numSubjects': '9'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}, {'groupId': 'FG002', 'numSubjects': '9'}, {'groupId': 'FG003', 'numSubjects': '9'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}]}]}, {'title': 'Wash-out After Period 1', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}, {'groupId': 'FG002', 'numSubjects': '9'}, {'groupId': 'FG003', 'numSubjects': '9'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '4'}, {'groupId': 'FG002', 'numSubjects': '8'}, {'groupId': 'FG003', 'numSubjects': '9'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '2'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '2'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '0'}]}]}, {'title': 'Period 2', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '4'}, {'groupId': 'FG002', 'numSubjects': '8'}, {'groupId': 'FG003', 'numSubjects': '9'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '4'}, {'groupId': 'FG002', 'numSubjects': '8'}, {'groupId': 'FG003', 'numSubjects': '9'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'This was a randomised, open-label, 2 -way cross-over design with at least 24 h wash-out, to establish the bioequivalence of alteplase derived from two different manufacturing processes (new process, tissue plasminogen activator (TPA)-05, vs. current process, TPA-02) in healthy male volunteers.', 'preAssignmentDetails': 'All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria.\n\nSubjects were not to be allocated to a treatment group if any of the entry criteria were violated. In this cross-over trial 2 single doses of alteplase were infused on 2 consecutive days keeping a wash-out period of at least 24 h.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}, {'value': '9', 'groupId': 'BG003'}, {'value': '30', 'groupId': 'BG004'}]}], 'groups': [{'id': 'BG000', 'title': 'Part A: Alteplase, TPA-02 Then Alteplase, TPA-05', 'description': 'Participants were administered on Day 1 of Period 1 a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 minutes (min) infusion.\n\nOn Day 1 of Period 2 participants were administered a single dose of 0.2 mg/kg body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 min infusion.\n\nThe 2 treatment periods were separated by a washout period of at least 24 hours (h).'}, {'id': 'BG001', 'title': 'Part A: Alteplase, TPA-05 Then Alteplase, TPA-02', 'description': 'Participants were administered on Day 1 of Period 1 a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 minutes (min) infusion.\n\nOn Day 1 of Period 2 participants were administered a single dose of 0.2 mg/kg body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 min infusion.\n\nThe 2 treatment periods were separated by a washout period of at least 24 hours (h).'}, {'id': 'BG002', 'title': 'Part B: Alteplase, TPA-02 Then Alteplase, TPA-05', 'description': 'Participants were administered on Day 1 of Period 1 a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 minutes (min) infusion. 5 min prior to the infusion of alteplase, TPA-02, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.\n\nOn Day 1 of Period 2 participants were administered a single dose of 0.2 mg/kg body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 min infusion. 5 min prior to the infusion of alteplase, TPA-05, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.\n\nThe 2 treatment periods were separated by a washout period of at least 24 hours (h).'}, {'id': 'BG003', 'title': 'Part B: Alteplase, TPA-05 Then Alteplase, TPA-02', 'description': 'Participants were administered on Day 1 of Period 1 a single dose of 0.2 milligram (mg)/kilogram (kg) body weight of alteplase from modified manufacturing process (alteplase, TPA-05) intravenously (i.v.) over a 30 minutes (min) infusion. 5 min prior to the infusion of alteplase, TPA-05, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.\n\nOn Day 1 of Period 2 participants were administered a single dose of 0.2 mg/kg body weight of alteplase from current manufacturing process (alteplase, TPA-02) intravenously (i.v.) over a 30 min infusion. 5 min prior to the infusion of alteplase, TPA-02, participants were administered 5000 international units (IU) of the auxiliary medicinal product (AMP) unfractionated heparin (Heparin-Natrium-ratiopharm®) as an intravenous bolus.\n\nThe 2 treatment periods were separated by a washout period of at least 24 hours (h).'}, {'id': 'BG004', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '34.3', 'spread': '5.8', 'groupId': 'BG000'}, {'value': '32.2', 'spread': '6.2', 'groupId': 'BG001'}, {'value': '31.7', 'spread': '5.8', 'groupId': 'BG002'}, {'value': '35.8', 'spread': '5.8', 'groupId': 'BG003'}, {'value': '33.5', 'spread': '5.8', 'groupId': 'BG004'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}, {'title': 'Male', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}, {'value': '9', 'groupId': 'BG003'}, {'value': '30', 'groupId': 'BG004'}]}]}], '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'}, {'value': '1', 'groupId': 'BG003'}, {'value': '1', 'groupId': 'BG004'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}, {'value': '8', 'groupId': 'BG003'}, {'value': '29', 'groupId': 'BG004'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}]}], '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'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '1', 'groupId': 'BG003'}, {'value': '1', 'groupId': 'BG004'}]}, {'title': 'White', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}, {'value': '8', 'groupId': 'BG003'}, {'value': '29', 'groupId': 'BG004'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'Treated set - part A (TS-A) included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.\n\nTreated set - part B (TS-B) included all subjects who had been randomised and treated with at least 1 dose of the investigational medicinal product.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-04-14', 'size': 804618, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2022-05-31T04:01', 'hasProtocol': True}, {'date': '2021-04-19', 'size': 244095, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2022-05-31T04:01', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'Part A: Open label Part B: Adaptive two-stage group-sequential design'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 30}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-06-23', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-04', 'completionDateStruct': {'date': '2021-06-21', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-04-25', 'studyFirstSubmitDate': '2020-06-04', 'resultsFirstSubmitDate': '2022-06-20', 'studyFirstSubmitQcDate': '2020-06-04', 'lastUpdatePostDateStruct': {'date': '2023-04-26', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-04-25', 'studyFirstPostDateStruct': {'date': '2020-06-05', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2023-04-26', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-06-21', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Part A: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Time Interval From 0 up to the Last Quantifiable Data Point (AUC0-tz)', 'timeFrame': 'Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.', 'description': 'The area under the concentration-time curve of alteplase in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.'}, {'measure': 'Part B: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Time Interval From 0 up to the Last Quantifiable Data Point (AUC0-tz)', 'timeFrame': 'Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.', 'description': 'The area under the concentration-time curve of Alteplase in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.'}, {'measure': 'Part A: Maximum Measured Concentration of Alteplase in Plasma (Cmax)', 'timeFrame': 'Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.', 'description': 'Maximum measured concentration of alteplase in plasma is reported.'}, {'measure': 'Part B: Maximum Measured Concentration of Alteplase in Plasma (Cmax)', 'timeFrame': 'Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.', 'description': 'Maximum measured concentration of Alteplase in plasma (Cmax) is reported.'}], 'secondaryOutcomes': [{'measure': 'Part A: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)', 'timeFrame': 'Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.', 'description': 'Area under the concentration-time curve of alteplase in plasma over interval from 0 extrapolated to infinity is reported.'}, {'measure': 'Part B: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Interval From 0 Extrapolated to Infinity (AUC0-∞)', 'timeFrame': 'Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.', 'description': 'Area under the concentration-time curve of alteplase in plasma over the interval from 0 extrapolated to infinity is reported.'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Healthy']}, 'referencesModule': {'references': [{'pmid': '37248330', 'type': 'DERIVED', 'citation': 'Glund S, Hoefler J, Lang B, Cafiero S, Panova-Noeva M, Place C, Wolff M. Bioequivalence of Intravenous Alteplase from Two Different Manufacturing Processes in Healthy Male Volunteers: Results from a Two-Stage, Adaptive-Design Study. Clin Pharmacokinet. 2023 Jul;62(7):1023-1030. doi: 10.1007/s40262-023-01253-3. Epub 2023 May 30.'}], 'seeAlsoLinks': [{'url': 'http://www.mystudywindow.com', 'label': 'Related Info'}]}, 'descriptionModule': {'briefSummary': 'To establish the bioequivalence of alteplase derived from two different manufacturing processes.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT'], 'maximumAge': '45 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests\n* Age of 18 to 45 years (inclusive)\n* Body mass index (weight divided by height squared) (BMI) of 18.5 to 29.9 kg/m2 (inclusive)\n* Body weight of 65 - 100 kg (inclusive) at screening\n* Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation\n\nExclusion Criteria:\n\n* Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator\n* Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm\n* Any laboratory value outside the reference range that the investigator considers to be of clinical relevance, e.g. thrombotic predisposition according to thrombophilic testing\n* Any evidence of a concomitant disease assessed as clinically relevant by the investigator\n* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders\n* Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders\n* History of relevant orthostatic hypotension, fainting spells, or blackouts\n* Chronic or relevant acute infections\n* History of relevant allergy or hypersensitivity\n* During COVID-19 pandemic: laboratory test indicative of an ongoing SARS-CoV-2 infection Further exclusion criteria apply.'}, 'identificationModule': {'nctId': 'NCT04419493', 'briefTitle': 'A Study in Healthy Men to Compare 2 Different Formulations of Alteplase', 'organization': {'class': 'INDUSTRY', 'fullName': 'Boehringer Ingelheim'}, 'officialTitle': 'Bioequivalence of Alteplase Derived From Two Different Manufacturing Processes Following Intravenous Administration in Healthy Male Volunteers', 'orgStudyIdInfo': {'id': '0135-0340'}, 'secondaryIdInfos': [{'id': '2019-004932-40', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Part B: Alteplase, TPA-02 then Alteplase, TPA-05', 'interventionNames': ['Drug: Alteplase (from modified manufacturing process)', 'Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin)']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Part B: Alteplase, TPA-05 then Alteplase, TPA-02', 'interventionNames': ['Drug: Alteplase (from current manufacturing process)', 'Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin)']}, {'type': 'EXPERIMENTAL', 'label': 'Part A: Alteplase, TPA-05 then Alteplase, TPA-02', 'description': 'Open-label', 'interventionNames': ['Drug: Alteplase (from modified manufacturing process)', 'Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin)']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Part A: Alteplase, TPA-02 then Alteplase, TPA-05', 'interventionNames': ['Drug: Alteplase (from current manufacturing process)', 'Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin)']}], 'interventions': [{'name': 'Alteplase (from modified manufacturing process)', 'type': 'DRUG', 'description': 'Alteplase, TPA-05', 'armGroupLabels': ['Part A: Alteplase, TPA-05 then Alteplase, TPA-02', 'Part B: Alteplase, TPA-02 then Alteplase, TPA-05']}, {'name': 'Alteplase (from current manufacturing process)', 'type': 'DRUG', 'description': 'Alteplase, TPA-02', 'armGroupLabels': ['Part A: Alteplase, TPA-02 then Alteplase, TPA-05', 'Part B: Alteplase, TPA-05 then Alteplase, TPA-02']}, {'name': 'Heparin-Natrium-5000-ratiopharm (unfractionated heparin)', 'type': 'DRUG', 'description': 'Heparin-Natrium-5000-ratiopharm (unfractionated heparin)', 'armGroupLabels': ['Part A: Alteplase, TPA-02 then Alteplase, TPA-05', 'Part A: Alteplase, TPA-05 then Alteplase, TPA-02', 'Part B: Alteplase, TPA-02 then Alteplase, TPA-05', 'Part B: Alteplase, TPA-05 then Alteplase, TPA-02']}]}, 'contactsLocationsModule': {'locations': [{'zip': '88397', 'city': 'Biberach', 'country': 'Germany', 'facility': 'Humanpharmakologisches Zentrum Biberach', 'geoPoint': {'lat': 48.33333, 'lon': 8.03333}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:\n\n1. studies in products where Boehringer Ingelheim is not the license holder;\n2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;\n3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).\n\nFor more details refer to: https://www.mystudywindow.com/msw/datasharing'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Boehringer Ingelheim', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}