Drug-Drug Interaction Between Colchicine and Ritonavir
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: Pharmacokinetics
Intervention: Colchicine (Drug); Ritonavir (Drug); Colchicine (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Mutual Pharmaceutical Company, Inc.
Summary
Ritonavir is a potent inhibitor of CYP3A4, one of the enzymes responsible for the metabolism
of colchicine. This study will evaluate the effect of multiple doses of ritonavir 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 Ritonavir 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:
Ritonavir is a potent inhibitor of CYP3A4, one of the enzymes responsible for the metabolism
of colchicine. This study will evaluate the effect of multiple doses of ritonavir 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. 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) on Day 1. 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 on Days 2-5. After
a 14 day washout period, on study Days 15-18, subjects will return to the clinic daily for
non-confined dosing of ritonavir (1 x 100 mg capsule) every 12 hours. Administered
ritonavir doses on these days will not necessarily be in a fasted state. On Day 15, after
taking the first dose of ritonavir, subjects will remain in the clinic for observation for 1
hour post-dose administration. On day 19 after a fast of at least 10 hours, a single dose
of colchicine (1 x 0. 6 mg tablet) and ritonavir (1 x 100 mg capsule) will be co-administered
to all study participants. Fasting will continue for 4 hours following the co-administered
doses of ritonavir and colchicine. All participants will be confined to the clinic for
dosing and 24-hour blood sampling at times sufficient to adequately determine the
pharmacokinetics of colchicine. Blood sampling will continue on a non-confined basis on Days
20-23. The final dose of ritonavir (1 x 100 mg capsule) will be administered to subjects the
evening of Day 19, in a non-fasting state. 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 prior to dosing and at
1, 2, and 3 hours following drug administration on Days 1, 15 and 19 to coincide with peak
plasma concentrations of both colchicine and ritonavir. 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, hyperlipidemia, pulmonary,
hepatic, gallbladder or biliary tract, renal, hematologic, gastrointestinal,
endocrine, immunologic, dermatologic, neurological, 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
Locations and Contacts
PRACS Institute, Ltd. - Cetero Research, East Grand Forks, Minnesota 56721, United States
Additional Information
Recalls, Market Withdrawals and Safety Alerts Daily Med - Posting of Recently Submitted Labeling to the FDA
Starting date: July 2008
Last updated: October 12, 2009
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