- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00983372
Drug-Drug Interaction Study Between Colchicine and Diltiazem ER
October 12, 2009 updated by: Mutual Pharmaceutical Company, Inc.
A One-Directional, Open-Label Drug Interaction Study to Investigate the Effects of Multiple-Dose Diltiazem ER on Single-Dose Pharmacokinetics of Colchicine in Healthy Volunteers
Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp).
Extended-release diltiazem (diltiazem ER) is a potent inhibitor of both CYP3A4 and P-gp.
This study will evaluate the effect of multiple doses of diltiazem ER on the pharmacokinetic profile of a single 0.6 mg dose of colchicine.
A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers.
All study subjects will be monitored for adverse events throughout the study period.
Study Overview
Status
Completed
Intervention / Treatment
Detailed Description
Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp).
Extended-release diltiazem (diltiazem ER) is a potent inhibitor of both CYP3A4 and P-gp.
This study will evaluate the effect of multiple doses of diltiazem ER on the pharmacokinetic profile of a single 0.6mg dose of colchicine.
On Day 1 after a fast of at least 10 hours, twenty-four healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 will be given a single oral dose of colchicine (1 x 0.6 mg tablet).
Fasting will continue for 4 hours after the dose.
Blood samples will be drawn from all participants before dosing and for twenty-four hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of colchicine.
Blood sampling will then continue on a non-confined basis at 36, 48, 72, and 96 hours post-dose.
After a 14-day washout period, beginning on Day 15 and continuing through Day 20 all subjects will return to the clinic for non-confined dosing of diltiazem ER (1 x 240 mg capsule daily).
Administered diltiazem ER doses on these days will not necessarily be in a fasted state.
On Day 21 after a fast of at least 10 hours, all study participants will receive a co-administered single oral dose of colchicine (1 x 0.6 mg tablet) and diltiazem ER (1 x 240 mg capsule).
Blood samples will be drawn from all participants before dosing and for twenty-four hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of colchicine in the presence of diltiazem ER at steady state.
Blood sampling will then continue on a non-confined basis at 36, 48, 72, and 96 hours post-dose administration.
Fasting will continue for 4 hours following the co-administered dose of colchicine and diltiazem ER.
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.
Vital signs (blood pressure and pulse) will be measured pre-dose and at 1, 2, and 3 hours post-dosing on Day 1, pre-dose and 12 hours post-dosing on Day 15 (subjects will return to the study center for the 12-hour post-dose vital sign measurements), and pre-dose and 1, 2, 3 and 12 hours post-dosing on Day 21 to coincide with peak plasma concentrations of both colchicine and diltiazem.
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.
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
North Dakota
-
Fargo, North Dakota, United States, 58104
- PRACS Institute, Ltd. - Cetero Research
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 45 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Healthy adults 18-45 years of age, non-smoking and non-pregnant (post-menopausal, 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.
Exclusion Criteria:
- Recent participation (within 28 days) in other research studies
- Recent significant blood donation or plasma donation
- Pregnant or lactating
- Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV)
- Recent (2-year) history or evidence of alcoholism or drug abuse
- History or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
- 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
- Drug allergies to colchicine or diltiazem.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Colchicine alone
-colchicine baseline pharmacokinetics
|
A single dose of 0.6 mg colchicine administered alone at 7:15 am on Day 1 after an overnight fast of at least 10 hours.
Other Names:
A single dose of 0.6 mg colchicine administered along with diltiazem ER at 7:15 am on Day 21 after an overnight fast of at least 10 hours.
|
Experimental: Colchicine with steady-state Diltiazem
-colchicine pharmacokinetics in presence of steady-state diltiazem
|
A single dose of 0.6 mg colchicine administered alone at 7:15 am on Day 1 after an overnight fast of at least 10 hours.
Other Names:
A single dose of 0.6 mg colchicine administered along with diltiazem ER at 7:15 am on Day 21 after an overnight fast of at least 10 hours.
One 240 mg diltiazem ER capsule administered daily at 7:15 am on Days 15 to 21.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Plasma Concentration (Cmax)
Time Frame: serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after dose administration
|
The maximum or peak concentration that colchicine reaches in the plasma.
|
serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after dose administration
|
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
Time Frame: serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after dose administration
|
The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable colchicine concentration (t), as calculated by the linear trapezoidal rule.
|
serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after dose administration
|
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
Time Frame: serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after dose administration
|
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 colchicine plasma concentration to the elimination rate constant.
|
serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after dose administration
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2008
Primary Completion (Actual)
August 1, 2008
Study Completion (Actual)
August 1, 2008
Study Registration Dates
First Submitted
August 13, 2009
First Submitted That Met QC Criteria
August 13, 2009
First Posted (Estimate)
September 24, 2009
Study Record Updates
Last Update Posted (Estimate)
October 15, 2009
Last Update Submitted That Met QC Criteria
October 12, 2009
Last Verified
October 1, 2009
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Vasodilator Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Membrane Transport Modulators
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Gout Suppressants
- Colchicine
- Diltiazem
Other Study ID Numbers
- MPC-004-08-1015
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Colchicine
-
Population Health Research InstituteCanadian Institutes of Health Research (CIHR)CompletedAtrial Fibrillation | Thoracic SurgeryCanada
-
Population Health Research InstituteRecruitingInflammation | Peripheral Arterial Disease | Atherosclerosis of ExtremitiesCanada
-
Wuhan Union Hospital, ChinaCompletedCoronary Artery Disease | Percutaneous Coronary InterventionChina
-
Eunice Kennedy Shriver National Institute of Child...National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National...CompletedObesity | Metabolic DiseaseUnited States
-
Montreal Heart InstituteCompletedMyocardial Infarction | Coronary Artery DiseaseCanada
-
University of the RyukyusCompletedCoronary Artery Disease | Inflammation | Diabetes Mellitus, Type 2 | Diarrhea | Colchicine | White Blood CellJapan
-
Assistance Publique - Hôpitaux de ParisCompletedColchicine Resistance | Mediterranean FeverFrance
-
Elpen Pharmaceutical Co. Inc.Withdrawn
-
Chinese Academy of Medical Sciences, Fuwai HospitalNot yet recruitingPercutaneous Coronary Intervention | Elderly Patients | Multivessel Coronary Artery Disease | C-Reactive ProteinChina