Drug-Drug Interaction Study of Colchicine and Azithromycin

NCT00983294 | Completed Phase 1 Results

• 1 other identifier: MPC-004-08-1011
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pharmacokinetics

Keywords

blood levels over time;; colchicine;; azithromycin;; healthy

Outcome Measures

Primary Outcomes (3)

• Maximum Plasma Concentration (Cmax)

  The maximum or peak concentration that colchicine reaches in the plasma.

  serial pharmacokinetic plasma concentrations were drawn prior to colchicine dose administration (0 hour) on Days 1 and 19, then at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after colchicine dose administration

• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]

  The area under the colchicine plasma concentration versus time curve, from time 0 to the time of the last measurable colchicine concentration (t), as calculated by the linear trapezoidal rule.

  serial pharmacokinetic plasma concentrations were drawn prior to colchicine dose administration (0 hour) on Days 1 and 19, then at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after colchicine dose administration

• Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]

  The area under the colchicine plasma concentration versus time curve from time 0 to infinity. AUC(0-∞) was calculated as the sum of AUC(0-t) plus the ratio of the last measurable colchicine plasma concentration to the elimination rate constant.

  serial pharmacokinetic plasma concentrations were drawn prior to colchicine dose administration (0 hour) on Days 1 and 19, then at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after colchicine dose administration

Study Arms (2)

Colchicine alone

ACTIVE COMPARATOR

baseline colchicine pharmacokinetics

Drug: Colchicine

Colchicine with steady-state Azithromycin

EXPERIMENTAL

colchicine pharmacokinetics in presence of steady-state azithromycin

Drug: Azithromycin; Drug: Colchicine

Interventions

Colchicine DRUG

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

Also known as: COLCRYS™

Colchicine alone

Azithromycin 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.

Also known as: Zithromax® Tablets USP, 250 mg

Colchicine with steady-state Azithromycin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mutual Pharmaceutical Company, Inc.: lead

Related Publications (1)

• 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.

  PMID: 21480191 DERIVED

Related Links

• Recalls, Market Withdrawals and Safety Alerts
• Daily Med - Posting of Recently Submitted Labeling to the FDA

MeSH Terms

Interventions

Colchicine; Azithromycin

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Medical Director
• Organization: Mutual Pharmaceutical Company, Inc.

clinicaltrials@urlmutual.com

215-697-1743

Study Officials

• Anthony R Godfrey, Pharm.D.

  PRACS - Cetero

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 13, 2009
• First Posted: September 24, 2009
• Study Start: July 1, 2008
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: October 28, 2009
• Results First Posted: September 24, 2009

Record last verified: 2009-10