Drug-Drug Interaction Study of Colchicine and Azithromycin

NCT ID: NCT00983294

Last Updated: 2009-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2008-08-31

Brief Summary

Azithromycin is a possible weak to moderate inhibitor of CYP3A4, one of the enzymes responsible for the metabolism of colchicine. This study will evaluate the effect of multiple doses of azithromycin 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

Azithromycin is a possible weak to moderate inhibitor of CYP3A4, one of the enzymes responsible for the metabolism of colchicine. This study will evaluate the effect of multiple doses of azithromycin on the pharmacokinetic profile of a single 0.6 mg 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 0.6 mg. 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 2 week washout period, beginning on Day 15 and continuing through day 18, subjects will return to the clinic daily for non-confined dosing of azithromycin given orally 2 x 250 mg tablets on Day 15 followed by 1 x 250 mg tablet on Days 16-18. Administered azithromycin doses on these days will not necessarily be in a fasted state. On Day 15 after taking the first dose of azithromycin, 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, all study subjects will receive a co-administered single dose of colchicine (0.6 mg) and azithromycin (1 x 250 mg tablet). All subjects will be confined to the clinic for the 24-hour period following the dose. Blood will be drawn at time sufficient to define the pharmacokinetics of colchicine in the presence of azithromycin at steady state. Blood sampling will continue on a non-confined basis on Days 20-23. 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. Seated blood pressure and pulse will be measured prior to dosing and at approximately 1, 2, and 3 hours following drug administration on Days 1 and 19. 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• 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 7:30 am on Day 1

Colchicine with steady-state Azithromycin

colchicine pharmacokinetics in presence of steady-state azithromycin

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

Two 250 mg azithromycin tablets administered at 7:30 am on Day 15, then one 250 mg tablet administered daily at 7:30 am on Days 16 to 19.

Colchicine

Intervention Type: DRUG

A single dose of 0.6 mg colchicine administered with azithromycin at 7:30 am on Day 19.

Interventions

Colchicine

A single dose of 0.6 mg colchicine administered alone at 7:30 am on Day 1

Intervention Type: DRUG

Azithromycin

Two 250 mg azithromycin tablets administered at 7:30 am on Day 15, then one 250 mg tablet administered daily at 7:30 am on Days 16 to 19.

Intervention Type: DRUG

Colchicine

A single dose of 0.6 mg colchicine administered with azithromycin at 7:30 am on Day 19.

Intervention Type: DRUG

Other Intervention Names

COLCRYS™; Zithromax® Tablets USP, 250 mg; COLCRYS™

Eligibility Criteria

Inclusion Criteria

• Healthy adults 18-45 years of age, non-smoking and non-pregnant (postmenopausal, 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
• 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, gall bladder or biliary tract, renal, haematological, 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

• 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 Godfrey, Pharm.D.

Role: PRINCIPAL_INVESTIGATOR

PRACS - Cetero

References

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-004-08-1011

Identifier Type: -

Identifier Source: org_study_id