Drug-Drug Interaction Study Between Colchicine and Atorvastatin

NCT00960323 | Completed Phase 1 Results

• 1 other identifier: MPC-004-08-1019
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Colchicine is a substrate for cytochrome P450 3A4 (CYP3A4). In-vitro studies have indicated that the ortho-and para-hydroxylated metabolites of atorvastatin may be CYP3A4/5 competitive and mechanism-based inhibitors (MBI). This study will evaluate the effect of multiple doses of atorvastatin 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

Keywords

pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• Maximum Plasma Concentration (Cmax) of Colchicine

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

  serial pharmacokinetic blood samples drawn prior to dosing on Days 1 and 28 and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 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 concentration (t), as calculated by the linear trapezoidal rule for colchicine.

  Serial pharmacokinetic blood samples drawn prior to dosing on Days 1 and 28 and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 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 plasma concentration to the elimination rate constant for colchicine.

  Serial pharmacokinetic blood samples drawn prior to dosing on Days 1 and 28 and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours after dose administration.

Study Arms (2)

Colchicine Alone

ACTIVE COMPARATOR

baseline colchicine pharmacokinetics

Drug: Colchicine

Colchicine with Atorvastatin

EXPERIMENTAL

Colchicine pharmacokinetics in the presence of atorvastatin at steady state.

Drug: Atorvastatin; Drug: Colchicine

Interventions

Colchicine DRUG

A single dose of 0.6 mg colchicine administered alone in the morning on Day 1.

Colchicine Alone

Atorvastatin DRUG

Atorvastatin (1 x 40 mg tablet) administered once daily on Days 15-28.

Colchicine with Atorvastatin

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)
• Body mass index (BMI) greater than or equal to 18 and less than or equal to 32, inclusive
• Hemoglobin greater than or equal to 11.5g/dL

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 atorvastatin or any other HMG-CoA reductase inhibitor agents (i.e. simvastatin, lovastatin, rosuvastatin, fluvastatin, and pravastatin)

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)

• Davis MW, Wason S. Effect of steady-state atorvastatin on the pharmacokinetics of a single dose of colchicine in healthy adults under fasted conditions. Clin Drug Investig. 2014 Apr;34(4):259-67. doi: 10.1007/s40261-013-0168-8.

  PMID: 24452746 DERIVED

MeSH Terms

Interventions

Colchicine; Atorvastatin

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

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

clinicaltrials@urlmutual.com

215-697-1743

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: August 17, 2009
• Study Start: February 1, 2009
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: March 30, 2010
• Results First Posted: March 16, 2010

Record last verified: 2010-03

Locations

US (1)