Drug-Drug Interaction Study Between Colchicine and Diltiazem ER
Information source: Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy; Adult; Volunteer; Colchicine; Pharmacokinetics; Diltiazem; Cytochrome p450 3A4; P-glycoprotein
Intervention: Colchicine (Drug); Diltiazem ER (Drug); Colchicine (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Mutual Pharmaceutical Company, Inc. Official(s) and/or principal investigator(s):
Anthony R Godfrey, PharmD, Principal Investigator, Affiliation: PRACS - Cetero
Summary
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.
Clinical Details
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
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: Maximum Plasma Concentration (Cmax)Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
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
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Both.
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.
Locations and Contacts
PRACS Institute, Ltd. - Cetero Research, Fargo, North Dakota 58104, United States
Additional Information
Starting date: August 2008
Last updated: October 12, 2009
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