Drug-Drug Interaction Between Colchicine and Verapamil ER

NCT00983242 | Completed Phase 1 Results

• 1 other identifier: MPC-004-08-1014
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). Verapamil hydrochloride is a potent inhibitor of cytochrome P450 (CYP) 3A4 and P-gp. This study will evaluate the effect of multiple doses of extended-release verapamil hydrochloride (verapamil HCl ER) 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

Outcome Measures

Primary Outcomes (3)

• Maximum Plasma Concentration (Cmax)

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

  On Days 1 and 19 - serial pharmacokinetic blood samples were collected pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose.

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

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

  On Days 1 and 19 - serial pharmacokinetic blood samples were collected pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose.

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

  The area under the 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.

  On Days 1 and 19 - serial pharmacokinetic blood samples were collected pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose.

Study Arms (2)

Colchicine alone

ACTIVE COMPARATOR

baseline colchicine pharmacokinetics

Drug: Colchicine

Colchicine with Verapamil HCl ER

EXPERIMENTAL

colchicine pharmacokinetics in presence of steady-state verapamil

Drug: Verapamil HCl ER; Drug: Colchicine

Interventions

Colchicine DRUG

A single dose of 0.6 mg colchicine administered alone at 8am on Day 1 after an overnight fast of at least 10 hours.

Colchicine alone

Verapamil HCl ER DRUG

One 240 mg verapamil HCl ER tablet taken at 8am on Days 15-18 without regard to meals and along with colchicine at 8am on Day 19 after an overnight fast of at least 10 hours.

Colchicine with Verapamil HCl ER

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 (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.

You may not qualify if:

• 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 verapamil

Sponsors & Collaborators

• Mutual Pharmaceutical Company, Inc.: lead

Study Sites (1)

PRACS Institute, Ltd. - Cetero Research

East Grand Forks, Minnesota, 56721, United States

Location

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; Verapamil

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

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

clinicaltrials@urlpharma.com

215-697-1743

Study Officials

• Anthony R Godfrey, PharmD

  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: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 13, 2009
• First Posted: September 24, 2009
• Study Start: September 1, 2008
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: October 15, 2009
• Results First Posted: September 24, 2009

Record last verified: 2009-10

Locations

US (1)