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Drug-Drug Interaction Study Between Colchicine and Cyclosporine

Phase 1
Completed
Conditions
Pharmacokinetics
Healthy
Interventions
Registration Number
NCT00983931
Lead Sponsor
Mutual Pharmaceutical Company, Inc.
Brief Summary

Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). Cyclosporine is a potent inhibitor of both CYP3A4 and P-gp. This study will evaluate the effect of single-dose cyclosporine 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

Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). Cyclosporine is a potent inhibitor of both CYP3A4 and P-gp. This study will evaluate the effect of single-dose cyclosporine on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. On study 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 one oral dose of colchicine (1 x 0.6 mg tablet). Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for 24 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. A 14 day washout period will be completed after the first dose of colchicine on Day 1. On Day 15 after a fast of at least 10 hours, all study participants will receive co-administered single oral doses of colchicine (1 x 0.6 mg tablet) and cyclosporine (1 x 100 mg capsule). Fasting will continue for 4 hours after the dose. Subjects will be confined to the clinic for dosing and a 24 hour period after the dose. Blood samples will be drawn from all participants before dosing and during the 24 hour post-dose period at times sufficient to adequately determine the pharmacokinetics of colchicine. Blood sampling will continue on a non-confined basis on Days 16-19. 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. Vital signs (blood pressure and pulse) will be measured prior to dosing and at 1, 2, and 3 hours following drug administration on Days 1 and 15 to coincide with peak plasma concentrations of both colchicine and cyclosporine. 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
Inclusion Criteria
  • 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.
Exclusion Criteria
  • 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 cyclosporine

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Colchicine aloneColchicine-baseline colchicine pharmacokinetics
Colchicine with CyclosporineCyclosporine-colchicine pharmacokinetics in presence of cyclosporine
Colchicine with CyclosporineColchicine-colchicine pharmacokinetics in presence of cyclosporine
Primary Outcome Measures
NameTimeMethod
Maximum Plasma Concentration (Cmax)serial pharmacokinetic blood samples drawn immediately prior to colchicine dosing on Days 1 and 15, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after colchicine dose administration

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

Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]serial pharmacokinetic blood samples drawn immediately prior to colchicine dosing on Days 1 and 15, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after colchicine dose administration

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.

Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]serial pharmacokinetic blood samples drawn immediately prior to colchicine dosing on Days 1 and 15, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after colchicine dose administration

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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

PRACS Institute, Ltd. - Cetero Research

🇺🇸

Fargo, North Dakota, United States

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