Drug-Drug Interaction Between Colchicine and Ritonavir

Pharmacokinetics Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00983515
• Other study ID #: MPC-004-08-1013
• Status: Completed
• Phase: Phase 1
• First received: August 13, 2009
• Last updated: October 12, 2009
• Start date: July 2008
• Est. completion date: August 2008

Study information

• Verified date: October 2009
• Source: Mutual Pharmaceutical Company, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Pharmacokinetics

Intervention

Drug:
• Colchicine
A single dose of colchicine 0.6 mg administered alone at 7:00 a.m. on Day 1 after an overnight fast of at least 10 hours.
• Ritonavir
One 100 mg ritonavir capsule administered twice daily at 7:00 a.m. and 7:00 p.m. on Days 15 to 18 without regard to meals, then along with colchicine at 7:00 a.m. on Day 19 after an overnight fast of at least 10 hours; final dose of 100 mg ritonavir administered at 7:00 p.m. on Day 19
• Colchicine
A single dose of colchicine 0.6 mg administered along with ritonavir at 7:00 a.m. on Day 19

Locations

Country	Name	City	State
United States	PRACS Institute, Ltd. - Cetero Research	East Grand Forks	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mutual Pharmaceutical Company, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Plasma Concentration (Cmax)		serial pharmacokinetic blood samples drawn within 1 hour prior to colchicine dosing (0 hour) on Days 1 and 19, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after colchicine dose administration	No
Primary	Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]		serial pharmacokinetic blood samples drawn within 1 hour prior to colchicine dosing (0 hour) on Days 1 and 19, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after colchicine dose administration	No
Primary	Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-8)]		serial pharmacokinetic blood samples drawn within 1 hour prior to colchicine dosing (0 hour) on Days 1 and 19, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after colchicine dose administration	No

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