Ignite Creation Date:
2025-12-24 @ 9:46 PM
Ignite Modification Date:
2026-03-13 @ 8:12 PM
Study NCT ID:
NCT01601132
Status:
COMPLETED
Last Update Posted:
2013-06-17
First Post:
2012-05-15
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Drug Interaction Study of Colchicine and Theophylline
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D013806', 'term': 'Theophylline'}, {'id': 'D003078', 'term': 'Colchicine'}], 'ancestors': [{'id': 'D014970', 'term': 'Xanthines'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D011688', 'term': 'Purinones'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'clinicaltrialregistry@tpna.com', 'phone': '800-778-2860', 'title': 'Sr. VP, Clinical Science', 'organization': 'Takeda Global Research and Development Center, Inc.'}, 'certainAgreement': {'otherDetails': 'The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'From the time of first study drug administration until 5 days after last dose.', 'description': 'At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.', 'eventGroups': [{'id': 'EG000', 'title': 'Theophylline', 'description': 'Theophylline 300 mg, solution, orally, on Day 1, followed by a 4-day washout period.', 'otherNumAtRisk': 30, 'otherNumAffected': 10, 'seriousNumAtRisk': 30, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Colchicine', 'description': 'Colchicine, 0.6 mg tablet, orally, twice daily, from Days 5-18.', 'otherNumAtRisk': 30, 'otherNumAffected': 10, 'seriousNumAtRisk': 30, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Colchicine + Theophylline', 'description': 'Theophylline 300 mg, solution, orally, single dose and colchicine 0.6 mg, tablets, orally, twice daily, on Day 19.', 'otherNumAtRisk': 29, 'otherNumAffected': 10, 'seriousNumAtRisk': 29, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Palpitations', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 2}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Tachycardia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 8}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Dry mouth', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Dyspepsia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 4}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Feeling jittery', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Decreased appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 5}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 4}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Somnolence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Oropharyngeal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Hyperhidrosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 30, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 29, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Time to Reach the Maximum Plasma Concentration (Tmax) of Theophylline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'OG000'}, {'value': '28', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Theophylline', 'description': 'Theophylline 300 mg, solution, orally, on Day 1.'}, {'id': 'OG001', 'title': 'Theophylline + Colchicine', 'description': 'Theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.'}], 'classes': [{'categories': [{'measurements': [{'value': '1.25', 'groupId': 'OG000', 'lowerLimit': '0.25', 'upperLimit': '4.00'}, {'value': '1.5', 'groupId': 'OG001', 'lowerLimit': '0.25', 'upperLimit': '4.00'}]}]}], 'analyses': [{'pValue': '0.5663', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Significant difference defined a priori as p \\< 0.05', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEDIAN', 'timeFrame': 'Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.', 'description': 'The time to each the maximum or peak concentration of theophylline in the plasma, after a single dose on Day 1, and after a single dose on Day 19, following 14 days of colchicine dosing.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The pharmacokinetic (PK) population is defined as any participant who took a single dose of study medication and had sufficient blood sampling to characterize the non-compartmental PK parameters. Patients with available data are included in the analysis.'}, {'type': 'PRIMARY', 'title': 'Maximum Plasma Concentration (Cmax) of Theophylline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'OG000'}, {'value': '28', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Theophylline', 'description': 'Theophylline 300 mg, solution, orally, on Day 1.'}, {'id': 'OG001', 'title': 'Theophylline + Colchicine', 'description': 'Theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.'}], 'classes': [{'categories': [{'measurements': [{'value': '11.0', 'spread': '2.16', 'groupId': 'OG000'}, {'value': '11.7', 'spread': '2.79', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Ratio (%) (Test/Reference)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '105.86', 'ciLowerLimit': '101.77', 'ciUpperLimit': '110.12', 'estimateComment': 'Ratio (theophylline+colchicine/theophylline) of LSMs calculated using the exponentiation of the difference between treatment LSM from the log-transformed Cmax, expressed as a percentage relative to the reference treatment.', 'groupDescription': 'Analysis of variance (ANOVA) was performed on the log-transformed Cmax to calculate least squares mean (LSM) for each treatment. The ANOVA model included sequence, treatment, and treatment within a sequence as fixed effects, and participant as a random effect. The criterion for demonstrating a lack of a clinically significant interaction is a 90% CI for the ratio for AUC0-t, (AUC0-∞), and Cmax to be within the 0.80 to 1.25 interval, representing a maximum of 20% difference between treatments.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.', 'description': 'The maximum or peak concentration of theophylline in the plasma, after a single dose on Day 1, and after another single dose on Day 19 following 14 days of colchicine dosing.', 'unitOfMeasure': 'μg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The pharmacokinetic (PK) population is defined as any participant who took a single dose of study medication and had sufficient blood sampling to characterize the non-compartmental PK parameters.'}, {'type': 'PRIMARY', 'title': 'Area Under the Concentration Versus Time Curve From Time 0 to Time of the Last Quantifiable Concentration[AUC(0-t)]', 'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'OG000'}, {'value': '28', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Theophylline', 'description': 'Theophylline 300 mg, solution, orally, on Day 1.'}, {'id': 'OG001', 'title': 'Theophylline + Colchicine', 'description': 'Theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.'}], 'classes': [{'categories': [{'measurements': [{'value': '155.6', 'spread': '34.86', 'groupId': 'OG000'}, {'value': '164.0', 'spread': '40.01', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Ratio (%) (Test/Reference)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '105.63', 'ciLowerLimit': '101.81', 'ciUpperLimit': '109.59', 'estimateComment': 'Ratio (theophylline+colchicine/theophylline) of LSMs calculated using the exponentiation of the difference between treatment LSM from the log-transformed AUC(0-t)\\], expressed as a percentage relative to the reference treatment.', 'groupDescription': 'Analysis of variance (ANOVA) was performed on the log-transformed AUC(0-t) to calculate least squares mean (LSM) for each treatment. The ANOVA model included sequence, treatment, and treatment within a sequence as fixed effects, and participant as a random effect. The criterion for demonstrating a lack of a clinically significant interaction is a 90% CI for the ratio for AUC0-t, AUC0-∞, and Cmax to be within the 0.80 to 1.25 interval, representing a maximum of 20% difference between treatments.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.', 'description': 'The area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration (t), as calculated by the linear trapezoidal rule for theophylline.', 'unitOfMeasure': 'hours*μg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population'}, {'type': 'PRIMARY', 'title': 'Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]', 'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'OG000'}, {'value': '28', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Theophylline', 'description': 'Theophylline 300 mg, solution, orally, on Day 1.'}, {'id': 'OG001', 'title': 'Theophylline + Colchicine', 'description': 'Theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.'}], 'classes': [{'categories': [{'measurements': [{'value': '180.7', 'spread': '62.30', 'groupId': 'OG000'}, {'value': '185.7', 'spread': '54.46', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Ratio (%) (Test/Reference)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '106.43', 'ciLowerLimit': '101.10', 'ciUpperLimit': '112.04', 'estimateComment': 'Ratio (theophylline+colchicine/theophylline) of LSMs calculated using the exponentiation of the difference between treatment LSM from the log-transformed AUC(0-∞) , expressed as a percentage relative to the reference treatment.', 'groupDescription': 'Analysis of variance (ANOVA) was performed on the log-transformed AUC(0-∞) to calculate least squares mean (LSM) for each treatment. The ANOVA model included sequence, treatment, and treatment within a sequence as fixed effects, and participant as a random effect. The criterion for demonstrating a lack of a clinically significant interaction is a 90% CI for the ratio for AUC0-t, AUC0-∞, and Cmax to be within the 0.80 to 1.25 interval, representing a maximum of 20% difference between treatments.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.', 'description': 'The area under the plasma concentration versus time curve from time 0 to infinity. \\[AUC(0-∞)\\] was calculated as the sum of AUC (0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant for theophylline.', 'unitOfMeasure': 'hours*μg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population'}, {'type': 'PRIMARY', 'title': 'Apparent Total Body Clearance (CL/F) of Theophylline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'OG000'}, {'value': '28', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Theophylline', 'description': 'Theophylline 300 mg, solution, orally, on Day 1.'}, {'id': 'OG001', 'title': 'Theophylline + Colchicine', 'description': 'Theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.'}], 'classes': [{'categories': [{'measurements': [{'value': '1.832', 'spread': '0.5849', 'groupId': 'OG000'}, {'value': '1.741', 'spread': '0.4799', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Ratio (%) (Test/Reference)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '93.96', 'ciLowerLimit': '89.25', 'ciUpperLimit': '98.92', 'estimateComment': 'Ratio (theophylline+colchicine/theophylline) of LSMs calculated using the exponentiation of the difference between treatment LSM from the log-transformed CL/F, expressed as a percentage relative to the reference treatment.', 'groupDescription': 'Analysis of variance (ANOVA) was performed on the log-transformed CL/F to calculate least squares mean (LSM) for each treatment. The ANOVA model included sequence, treatment, and treatment within a sequence as fixed effects, and participant as a random effect. The criterion for demonstrating a lack of a clinically significant interaction is a 90% CI for the ratio for AUC0-t, AUC0-∞, and Cmax to be within the 0.80 to 1.25 interval, representing a maximum of 20% difference between treatments.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.', 'description': 'Apparent total body clearance after oral administration, calculated as Dose /(AUC0-∞).', 'unitOfMeasure': 'liters/hour', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population'}, {'type': 'PRIMARY', 'title': 'Apparent Total Volume of Distribution (Vd/F) of Theophylline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'OG000'}, {'value': '28', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Theophylline', 'description': 'Theophylline 300 mg, solution, orally, on Day 1.'}, {'id': 'OG001', 'title': 'Theophylline + Colchicine', 'description': 'Theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.'}], 'classes': [{'categories': [{'measurements': [{'value': '36.21', 'spread': '13.03', 'groupId': 'OG000'}, {'value': '34.44', 'spread': '10.39', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Ratio (%) (Test/Reference)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '98.59', 'ciLowerLimit': '90.97', 'ciUpperLimit': '106.85', 'estimateComment': 'Ratio (theophylline+colchicine/theophylline) of LSMs calculated using the exponentiation of the difference between treatment LSM from the log-transformed Vd/F, expressed as a percentage relative to the reference treatment.', 'groupDescription': 'Analysis of variance (ANOVA) was performed on the log-transformed Vd/F to calculate least squares mean (LSM) for each treatment. The ANOVA model included sequence, treatment, and treatment within a sequence as fixed effects, and participant as a random effect. The criterion for demonstrating a lack of a clinically significant interaction is a 90% CI for the ratio for AUC0-t, AUC0-∞, and Cmax to be within the 0.80 to 1.25 interval, representing a maximum of 20% difference between treatments.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.', 'description': 'Apparent total volume of distribution after oral administration, calculated as Dose /(AUC0-∞) \\* Apparent first-order elimination rate constant \\[Kel\\])', 'unitOfMeasure': 'liters', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Theophylline + Colchicine', 'description': 'Theophylline 300 mg, solution, orally, on Day 1, then colchicine 0.6 mg tablets, orally, twice daily on Days 5-18, then theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '30'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '28'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}]}], 'dropWithdraws': [{'type': 'Patient withdrew consent', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Protocol deviation', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'Participants took part in the study at one investigative site in the USA from 11 June 2012 to 01 July 2012.', 'preAssignmentDetails': 'Thirty non-smoking, adult male and female volunteers (ages 18 to 45 years) were enrolled in this single group study.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Theophylline + Colchicine', 'description': 'Theophylline 300 mg, solution, orally, on Day 1, then colchicine 0.6 mg tablets, orally, twice daily on Days 5-18, then theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.'}], 'measures': [{'title': 'Age Continuous', 'classes': [{'categories': [{'measurements': [{'value': '31.8', 'spread': '7.8', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '18', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '12', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'American Indian or Alaska Native', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}, {'title': 'Black or African American', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}, {'title': 'White', 'categories': [{'measurements': [{'value': '25', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'Hispanic or Latino', 'categories': [{'measurements': [{'value': '23', 'groupId': 'BG000'}]}]}, {'title': 'Not Hispanic or Latino', 'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '30', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'Participants'}, {'title': 'Tobacco history', 'classes': [{'title': 'Never used tobacco', 'categories': [{'measurements': [{'value': '26', 'groupId': 'BG000'}]}]}, {'title': 'Past smoker or has used other forms of tobacco', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 30}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2012-05'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2013-04', 'completionDateStruct': {'date': '2012-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2013-04-18', 'studyFirstSubmitDate': '2012-05-15', 'resultsFirstSubmitDate': '2013-03-07', 'studyFirstSubmitQcDate': '2012-05-15', 'lastUpdatePostDateStruct': {'date': '2013-06-17', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2013-04-18', 'studyFirstPostDateStruct': {'date': '2012-05-17', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2013-06-17', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Time to Reach the Maximum Plasma Concentration (Tmax) of Theophylline', 'timeFrame': 'Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.', 'description': 'The time to each the maximum or peak concentration of theophylline in the plasma, after a single dose on Day 1, and after a single dose on Day 19, following 14 days of colchicine dosing.'}, {'measure': 'Maximum Plasma Concentration (Cmax) of Theophylline', 'timeFrame': 'Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.', 'description': 'The maximum or peak concentration of theophylline in the plasma, after a single dose on Day 1, and after another single dose on Day 19 following 14 days of colchicine dosing.'}, {'measure': 'Area Under the Concentration Versus Time Curve From Time 0 to Time of the Last Quantifiable Concentration[AUC(0-t)]', 'timeFrame': 'Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.', 'description': 'The area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration (t), as calculated by the linear trapezoidal rule for theophylline.'}, {'measure': 'Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]', 'timeFrame': 'Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.', 'description': 'The area under the plasma concentration versus time curve from time 0 to infinity. \\[AUC(0-∞)\\] was calculated as the sum of AUC (0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant for theophylline.'}, {'measure': 'Apparent Total Body Clearance (CL/F) of Theophylline', 'timeFrame': 'Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.', 'description': 'Apparent total body clearance after oral administration, calculated as Dose /(AUC0-∞).'}, {'measure': 'Apparent Total Volume of Distribution (Vd/F) of Theophylline', 'timeFrame': 'Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.', 'description': 'Apparent total volume of distribution after oral administration, calculated as Dose /(AUC0-∞) \\* Apparent first-order elimination rate constant \\[Kel\\])'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['pharmacokinetics', 'colchicine', 'theophylline'], 'conditions': ['Healthy']}, 'descriptionModule': {'briefSummary': 'Colchicine is a supressor of hepatic CYP1A2 and theophylline is a sensitive CYP1A2 probe substrate. When the two are co-administered the potential exists for a clinically significant drug interaction. This study aims to determine the effect of steady-state colchicine on the pharmacokinetics of theophylline administered as a single dose. A secondary goal is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the entire study period.', 'detailedDescription': "Colchicine is a supressor of hepatic CYP1A2 and theophylline is a sensitive CYP1A2 probe substrate. When the two are co-administered the potential exists for a clinically significant drug interaction. This study aims to determine the effect of steady-state colchicine on the pharmacokinetics of theophylline administered as a single dose. After a fast of at least 10 hours, thirty healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 will be given one dose of 300mg (80mg/15ml concentrate) theophylline (theophylline elixir) on Day 1. Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose on a confined basis at times sufficient to adequately determine the pharmacokinetics of theophylline. Blood sampling will then continue on a non-confined basis on days 2-3. A four day washout period will be completed after the theophylline dose on Day 1 and prior to administration of the first colchicine dose on Day 5. Participants will return to the clinic on days 5-18 for non-confined dosing of colchicine (1x0.6mg twice daily every 12 hours). Administered dosing on these days will not necessarily be in a fasted state. Co-administration of a single 300mg dose of theophylline (80mg/15ml) and colchicine (1x0.6mg) will occur on the morning of Day 19 following a fast of at least 10 hours. Twelve hours later, subjects will receive the last dose of colchicine (1x0.6mg). Blood samples will be drawn from all participants before dosing on Day 19 and for 24 hours post-dose on a confined basis at times sufficient to adequately determine the pharmacokinetics of theophylline. Blood sampling will then continue on a non-confined basis on days 20 and 21. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Seated blood pressure and pulse will be measured prior to dosing and at approximately 1, 2, and 3 hours following drug administration on Days 1, 5 (after the morning dose) and 19. All adverse events whether elicited by query, spontaneously reported, or observed by clinic staff will be evaluated by the Investigator and reported in the subject's case report form."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '45 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Healthy adults 18-45 years of age, non smoking and non-pregnant (postmenopausal, surgically sterile or using effective contraceptive measures) with a body mass index (BMI) greater than or equal to 18 and less than or equal to 32, inclusive; hemoglobin greater than or equal to 11.5g/dL\n\nExclusion Criteria:\n\n* Recent participation (within 28 days) in other research studies\n* Recent significant blood donation or donation of plasma\n* Pregnant or lactating\n* Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV)\n* Recent (2-year) history or evidence of alcoholism or drug abuse\n* Subjects who test positive for drugs of abuse or alcohol at screening or check-in\n* History or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease or active sexually transmitted disease\n* History of neuropathy or muscle disorders, peptic ulcer disease, clinically significant cardiac arrhythmias, seizure disorder, and low white blood cell count or other bone marrow disorders\n* Subjects who have used any drugs or substances known to inhibit or induce cytochrome (CYP) P450 enzymes and/or P-glycoprotein (P-gp) within 28 days prior to the first dose and throughout the study\n* History of allergy or sensitivity to colchicine or theophylline or aminophylline\n* Subjects who have had a tattoo or body piercing within 30 days prior to administration of study drug\n* Subjects with irritable bowel syndrome, chronic diarrhea or other chronic gastro-intestinal problems\n* Subjects who are lactose intolerant'}, 'identificationModule': {'nctId': 'NCT01601132', 'briefTitle': 'Drug Interaction Study of Colchicine and Theophylline', 'organization': {'class': 'INDUSTRY', 'fullName': 'Takeda'}, 'officialTitle': 'An Open-Label, One Sequence, Pharmacokinetic Drug Interaction Study of Colchicine and Theophylline in Healthy Subjects', 'orgStudyIdInfo': {'id': 'MPC-004-11-4001'}, 'secondaryIdInfos': [{'id': 'U1111-1141-7355', 'type': 'REGISTRY', 'domain': 'WHO'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'theophylline', 'description': '300mg (80mg/15ml elixir) theophylline', 'interventionNames': ['Drug: theophylline']}, {'type': 'EXPERIMENTAL', 'label': 'Colchicine', 'description': 'colchicine 0.6mg by mouth twice daily on Days 5-19, co-administered with theophylline 300mg (80mg/15ml) on the morning of Day 19', 'interventionNames': ['Drug: colchicine']}], 'interventions': [{'name': 'theophylline', 'type': 'DRUG', 'otherNames': ['Elixophyllin®'], 'description': '300mg (80mg/15ml elixir)', 'armGroupLabels': ['theophylline']}, {'name': 'colchicine', 'type': 'DRUG', 'otherNames': ['COLCRYS®'], 'description': 'colchicine 0.6mg by mouth twice daily on Days 5-19, co-administered with theophylline 300mg (80mg/15ml) on the morning of Day 19', 'armGroupLabels': ['Colchicine']}]}, 'contactsLocationsModule': {'locations': [{'zip': '78217', 'city': 'San Antonio', 'state': 'Texas', 'country': 'United States', 'facility': 'Worlwide Clinical Trials Drug Development Solutions, Clinical Research Services', 'geoPoint': {'lat': 29.42412, 'lon': -98.49363}}], 'overallOfficials': [{'name': 'Matthew Davis, M.D.', 'role': 'STUDY_CHAIR', 'affiliation': 'Mutual Pharmaceutical Company, Inc.'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Takeda', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}