Drug-Drug Interaction Study Between Colchicine and Diltiazem ER

This study has been completed.
Sponsor:
Information provided by:
Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier:
NCT00983372
First received: August 13, 2009
Last updated: October 12, 2009
Last verified: October 2009
  Purpose

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.


Condition Intervention Phase
Healthy; Adult; Volunteer; Colchicine; Pharmacokinetics; Diltiazem; Cytochrome p450 3A4; P-glycoprotein
Drug: Colchicine
Drug: Diltiazem ER
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Mutual Pharmaceutical Company, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: August 2008
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Colchicine alone
-colchicine baseline pharmacokinetics
Drug: Colchicine
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 Name: COLCRYS™
Experimental: Colchicine with steady-state Diltiazem
-colchicine pharmacokinetics in presence of steady-state diltiazem
Drug: Diltiazem ER
One 240 mg diltiazem ER capsule administered daily at 7:15 am on Days 15 to 21.
Other Name: Cardizem® CD (Biovail Pharmaceuticals, Inc.)
Drug: Colchicine
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00983372

Locations
United States, North Dakota
PRACS Institute, Ltd. - Cetero Research
Fargo, North Dakota, United States, 58104
Sponsors and Collaborators
Mutual Pharmaceutical Company, Inc.
Investigators
Principal Investigator: Anthony R Godfrey, PharmD PRACS - Cetero
  More Information

No publications provided by Mutual Pharmaceutical Company, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Vice President, Branded Products and Medical Affairs, Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier: NCT00983372     History of Changes
Other Study ID Numbers: MPC-004-08-1015
Study First Received: August 13, 2009
Results First Received: August 13, 2009
Last Updated: October 12, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Mutual Pharmaceutical Company, Inc.:
healthy; adult; volunteer; colchicine; diltiazem; blood levels over time

Additional relevant MeSH terms:
Colchicine
Diltiazem
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents
Calcium Channel Blockers
Membrane Transport Modulators
Cardiovascular Agents
Antihypertensive Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on April 23, 2014