Drug-Drug Interaction Study Between Colchicine and Cyclosporine

NCT ID: NCT00983931

Last Updated: 2009-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2008-09-30

Brief Summary

Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). Cyclosporine is a potent inhibitor of both CYP3A4 and P-gp. This study will evaluate the effect of single-dose cyclosporine 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

Detailed Description

Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). Cyclosporine is a potent inhibitor of both CYP3A4 and P-gp. This study will evaluate the effect of single-dose cyclosporine on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. On study 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 one 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 24 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. A 14 day washout period will be completed after the first dose of colchicine on Day 1. On Day 15 after a fast of at least 10 hours, all study participants will receive co-administered single oral doses of colchicine (1 x 0.6 mg tablet) and cyclosporine (1 x 100 mg capsule). Fasting will continue for 4 hours after the dose. Subjects will be confined to the clinic for dosing and a 24 hour period after the dose. Blood samples will be drawn from all participants before dosing and during the 24 hour post-dose period at times sufficient to adequately determine the pharmacokinetics of colchicine. Blood sampling will continue on a non-confined basis on Days 16-19. 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 and 15 to coincide with peak plasma concentrations of both colchicine and cyclosporine. 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.

Conditions

Pharmacokinetics; Healthy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Colchicine alone

-baseline colchicine pharmacokinetics

Group Type: ACTIVE_COMPARATOR

Colchicine

Intervention Type: DRUG

A single dose of 0.6 mg colchicine administered alone at 7:15 a.m. on Day 1 after an overnight fast of at least 10 hours.

Colchicine with Cyclosporine

-colchicine pharmacokinetics in presence of cyclosporine

Group Type: EXPERIMENTAL

Cyclosporine

Intervention Type: DRUG

A single dose of 100 mg cyclosporine administered with colchicine at 7:15 a.m. on Day 15 after an overnight fast of at least 10 hours.

Colchicine

Intervention Type: DRUG

A single dose of 0.6 mg colchicine administered with cyclosporine at 7:15 a.m. on Day 15 after an overnight fast of at least 10 hours.

Interventions

Colchicine

A single dose of 0.6 mg colchicine administered alone at 7:15 a.m. on Day 1 after an overnight fast of at least 10 hours.

Intervention Type: DRUG

Cyclosporine

A single dose of 100 mg cyclosporine administered with colchicine at 7:15 a.m. on Day 15 after an overnight fast of at least 10 hours.

Intervention Type: DRUG

Colchicine

A single dose of 0.6 mg colchicine administered with cyclosporine at 7:15 a.m. on Day 15 after an overnight fast of at least 10 hours.

Intervention Type: DRUG

Other Intervention Names

COLCRYS™; Neoral® (Novartis Pharmaceuticals Corporation)

Eligibility 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 cyclosporine

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mutual Pharmaceutical Company, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Mutual Pharmaceutical Company, Inc.

Principal Investigators

Anthony R G, Pharm.D.

Role: PRINCIPAL_INVESTIGATOR

PRACS - Cetero

Locations

PRACS Institute, Ltd. - Cetero Research

Fargo, North Dakota, United States

Countries

United States

References

Wason S, Digiacinto JL, Davis MW. Effect of cyclosporine on the pharmacokinetics of colchicine in healthy subjects. Postgrad Med. 2012 Jul;124(4):189-96. doi: 10.3810/pgm.2012.07.2579.

Reference Type: DERIVED

PMID: 22913907 (View on PubMed)

Terkeltaub RA, Furst DE, Digiacinto JL, Kook KA, Davis MW. Novel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors. Arthritis Rheum. 2011 Aug;63(8):2226-37. doi: 10.1002/art.30389.

Reference Type: DERIVED

PMID: 21480191 (View on PubMed)

Related Links

http://www.fda.gov/opacom/7alerts.html

Recalls, Market Withdrawals and Safety Alerts

http://dailymed.nlm.nih.gov/dailymed/about.cfm

Daily Med - Posting of Recently Submitted Labeling to the FDA

Other Identifiers

MPC-004-08-1016

Identifier Type: -

Identifier Source: org_study_id