Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Drug-Food Interaction Study Between Colchicine and Grapefruit Juice

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier:
NCT00984009
First received: August 13, 2009
Last updated: November 11, 2011
Last verified: November 2011

August 13, 2009
November 11, 2011
September 2008
October 2008   (final data collection date for primary outcome measure)
  • Maximum Plasma Concentration (Cmax) [ Time Frame: serial pharmacokinetic blood samples drawn immediately prior to colchicine dosing on Days 1 and 18, 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 ] [ Designated as safety issue: No ]
    The maximum or peak concentration that colchicine reaches in the plasma.
  • 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 18, 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 ] [ Designated as safety issue: No ]
    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.
  • 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 18, 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 ] [ Designated as safety issue: No ]
    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.
  • Maximum Plasma Concentration (Cmax) [ Time Frame: serial pharmacokinetic blood samples drawn immediately prior to colchicine dosing on Days 1 and 18, 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 ] [ Designated as safety issue: No ]
  • 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 18, 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 ] [ Designated as safety issue: No ]
  • 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 18, 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 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00984009 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
A Drug-Food Interaction Study Between Colchicine and Grapefruit Juice
A One-Directional, Open-Label Drug-Food Interaction Study to Investigate the Effects of Multiple-Daily Consumptions of Grapefruit Juice on the Single-Dose Pharmacokinetics of Colchicine in Healthy Volunteers

Grapefruit juice is an inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the enzyme systems responsible for the metabolism of colchicine. This study will evaluate the effect of multiple daily consumptions of grapefruit juice 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.

Grapefruit juice is an inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the enzyme systems responsible for the metabolism of colchicine. This study will evaluate the effect of multiple daily consumptions of grapefruit juice 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-two healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 will be given one 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 continue on a non-confined basis on Days 2-5. After a 14 day washout period, starting on the morning of Day 15 and continuing through Day 17, subjects will return to the clinic for consumption of an administered dose of grapefruit juice (1 x 240 ml) twice daily. On the morning of Day 18 after a fast of at least 10 hours all subjects will receive a co-administered single oral dose of colchicine (1 x 0.6 mg) and grapefruit juice (1 x 240 ml). 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 in the presence of grapefruit juice. Blood sampling will continue on a non-confined basis on Days 19-22. Subjects will consume the final administered dose of grapefruit juice (1 x 240 ml) in the evening on Day 18. 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. Seated blood pressure and pulse will be measured prior to dosing and at approximately 1, 2, and 3 hours following drug administration on Days 1 and 18 to coincide with peak plasma concentrations of colchicine. 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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Pharmacokinetics
  • Drug: Colchicine
    A single dose of 0.6 mg colchicine administered alone at 7:15 a.m. on Day 1
    Other Name: COLCRYS™
  • Other: Grapefruit Juice
    240 mL of grapefruit juice ingested twice daily at 7:15 a.m. and 7:15 p.m. on Days 15 to 18.
  • Drug: Colchicine
    A single dose of 0.6 mg colchicine administered with grapefruit juice at 7:15 a.m. on Day 18 after an overnight fast of at least 10 hours.
  • Active Comparator: Colchicine alone
    baseline colchicine pharmacokinetics
    Intervention: Drug: Colchicine
  • Experimental: Colchicine with Grapefruit Juice
    colchicine pharmacokinetics in presence of grapefruit juice
    Interventions:
    • Other: Grapefruit Juice
    • Drug: Colchicine
Wason S, DiGiacinto JL, Davis MW. Effects of grapefruit and Seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects. Clin Ther. 2012 Oct;34(10):2161-73. doi: 10.1016/j.clinthera.2012.08.007. Epub 2012 Aug 31.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
October 2008
October 2008   (final data collection date for primary outcome measure)

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
Both
18 Years to 45 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00984009
MPC-004-08-1017
No
Mutual Pharmaceutical Company, Inc.
Mutual Pharmaceutical Company, Inc.
Not Provided
Principal Investigator: Anthony R Godfrey, Pharm.D. PRACS - Cetero
Mutual Pharmaceutical Company, Inc.
November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP