Drug-Drug Interaction Study Between Colchicine and Diltiazem ER

NCT00983372 | Completed Phase 1 Results

• 1 other identifier: MPC-004-08-1015
• 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). Extended-release diltiazem (diltiazem ER) is a potent inhibitor of both CYP3A4 and P-gp. This study will evaluate the effect of multiple doses of diltiazem 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

Healthy; Adult; Volunteer; Colchicine; Pharmacokinetics; Diltiazem; Cytochrome p450 3A4; P-glycoprotein

Keywords

healthy; adult; volunteer; colchicine; diltiazem; blood levels over time

Outcome Measures

Primary Outcomes (3)

• Maximum Plasma Concentration (Cmax)

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

  serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after dose administration

• 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, from time 0 to the time of the last measurable colchicine concentration (t), as calculated by the linear trapezoidal rule.

  serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after dose administration

• 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.

  serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after dose administration

Study Arms (2)

Colchicine alone

ACTIVE COMPARATOR

-colchicine baseline pharmacokinetics

Drug: Colchicine

Colchicine with steady-state Diltiazem

EXPERIMENTAL

-colchicine pharmacokinetics in presence of steady-state diltiazem

Drug: Diltiazem ER; Drug: Colchicine

Interventions

Colchicine DRUG

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

Also known as: COLCRYS™

Colchicine alone

Diltiazem ER DRUG

One 240 mg diltiazem ER capsule administered daily at 7:15 am on Days 15 to 21.

Also known as: Cardizem® CD (Biovail Pharmaceuticals, Inc.)

Colchicine with steady-state Diltiazem

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 diltiazem.

Sponsors & Collaborators

• Mutual Pharmaceutical Company, Inc.: lead

Study Sites (1)

PRACS Institute, Ltd. - Cetero Research

Fargo, North Dakota, 58104, 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

MeSH Terms

Interventions

Colchicine; Diltiazem

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

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

clinicaltrials@urlmutual.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: August 1, 2008
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: October 15, 2009
• Results First Posted: September 24, 2009

Record last verified: 2009-10

Locations

US (1)