A Drug-Food Interaction Study Between Colchicine and Grapefruit Juice

NCT ID: NCT00984009

Last Updated: 2011-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2008-10-31

Brief Summary

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.

Detailed Description

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.

Conditions

Pharmacokinetics

Keywords

healthy; pharmacokinetics; grapefruit juice; furanocoumarins; cytochrome p450 3A4

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Colchicine alone

baseline colchicine pharmacokinetics

Group Type: ACTIVE_COMPARATOR

Colchicine

Intervention Type: DRUG

A single dose of 0.6 mg colchicine administered alone at 7:15 a.m. on Day 1

Colchicine with Grapefruit Juice

colchicine pharmacokinetics in presence of grapefruit juice

Group Type: EXPERIMENTAL

Grapefruit Juice

Intervention Type: OTHER

240 mL of grapefruit juice ingested twice daily at 7:15 a.m. and 7:15 p.m. on Days 15 to 18.

Colchicine

Intervention Type: DRUG

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.

Interventions

Colchicine

A single dose of 0.6 mg colchicine administered alone at 7:15 a.m. on Day 1

Intervention Type: DRUG

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.

Intervention Type: OTHER

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.

Intervention Type: DRUG

Other Intervention Names

COLCRYS™

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mutual Pharmaceutical Company, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anthony R Godfrey, Pharm.D.

Role: PRINCIPAL_INVESTIGATOR

PRACS - Cetero

Locations

PRACS Institute, Ltd. - Cetero Research

Fargo, North Dakota, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 22940371 (View on PubMed)

Related Links

http://www.fda.gov/opacom/7alerts.html

Recalls, Market Withdrawals and Safety Alerts

http://dailymed.nlm.nih.gov/dailymed/about.cfm

Daily Med - Posting of Recently Submitted Labeling to the FDA

Other Identifiers

MPC-004-08-1017

Identifier Type: -

Identifier Source: org_study_id