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Drug-Drug Interaction Study Between Colchicine and Cyclosporine

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ClinicalTrials.gov Identifier: NCT00983931
Recruitment Status : Completed
First Posted : September 24, 2009
Results First Posted : September 24, 2009
Last Update Posted : October 15, 2009
Sponsor:
Information provided by:
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

Condition or disease Intervention/treatment Phase
Pharmacokinetics Healthy Drug: Colchicine Drug: Cyclosporine Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A One-Directional, Open-label Drug Interaction Study to Investigate the Effects of Single-Dose Cyclosporine on Single-Dose Pharmacokinetics of Colchicine in Healthy Volunteers
Study Start Date : August 2008
Actual Primary Completion Date : September 2008
Actual Study Completion Date : September 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Arm Intervention/treatment
Active Comparator: Colchicine alone
-baseline colchicine pharmacokinetics
Drug: Colchicine
A single dose of 0.6 mg colchicine administered alone at 7:15 a.m. on Day 1 after an overnight fast of at least 10 hours.
Other Name: COLCRYS™

Experimental: Colchicine with Cyclosporine
-colchicine pharmacokinetics in presence of cyclosporine
Drug: Cyclosporine
A single dose of 100 mg cyclosporine administered with colchicine at 7:15 a.m. on Day 15 after an overnight fast of at least 10 hours.
Other Name: Neoral® (Novartis Pharmaceuticals Corporation)

Drug: Colchicine
A single dose of 0.6 mg colchicine administered with cyclosporine at 7:15 a.m. on Day 15 after an overnight fast of at least 10 hours.




Primary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) [ Time Frame: 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.

  2. Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] [ Time Frame: 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.

  3. Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00983931


Locations
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United States, North Dakota
PRACS Institute, Ltd. - Cetero Research
Fargo, North Dakota, United States, 58104
Sponsors and Collaborators
Mutual Pharmaceutical Company, Inc.
Investigators
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Principal Investigator: Anthony R G, Pharm.D. PRACS - Cetero
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Vice President, Branded Products and Medical Affairs, Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier: NCT00983931    
Other Study ID Numbers: MPC-004-08-1016
First Posted: September 24, 2009    Key Record Dates
Results First Posted: September 24, 2009
Last Update Posted: October 15, 2009
Last Verified: October 2009
Keywords provided by Mutual Pharmaceutical Company, Inc.:
healthy
adult
colchicine
cyclosporine
blood levels over time
Additional relevant MeSH terms:
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Cyclosporine
Colchicine
Cyclosporins
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Gout Suppressants
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents