Drug-Food Interaction Study of Seville Orange Juice and Colchicine
Information source: Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: Colchicine (Drug); Seville Orange Juice (Other)
Phase: Phase 1
Status: Completed
Sponsored by: Mutual Pharmaceutical Company, Inc.
Summary
Seville orange juice is an inhibitor of the intestinal cytochrome P450 (CYP) 3A4 enzyme, one
of the enzymes responsible for the metabolism of colchicine. This study will evaluate the
effect of multiple daily consumptions of Seville orange 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.
Clinical Details
Official title: A One-Directional, Open-Label Drug-Food Interaction Study to Investigate the Effects of Multiple-Daily Consumptions of Seville Orange Juice on the Single-Dose Pharmacokinetics of Colchicine in Healthy Volunteers
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: Maximum Plasma Concentration (Cmax) of ColchicineArea Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
Detailed description:
Seville orange juice is an inhibitor of the intestinal cytochrome P450 (CYP) 3A4 enzyme, one
of the enzymes responsible for the metabolism of colchicine. This study will evaluate the
effect of multiple daily consumptions of Seville orange juice on the pharmacokinetic profile
of a single 0. 6 mg dose of colchicine. Twenty-four 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) on Day 1, after an overnight fast. 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 to adequately define the baseline pharmacokinetics of
colchicine. 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 240 ml dose of Seville orange juice in the morning and evening. At 8am on Day
18 after an overnight fast, all subjects will receive a co-administered single oral dose of
colchicine (1 x 0. 6 mg) and Seville orange 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 to adequately define the pharmacokinetics of colchicine in the
presence of Seville orange juice. Subjects will consume the final administered 240 ml dose
of Seville orange juice 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.
Eligibility
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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
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
- Intolerance or food allergy to Seville orange juice
Locations and Contacts
PRACS Institute, Ltd. - Cetero Research, Fargo, North Dakota 58104, United States
Additional Information
Recalls, Market Withdrawals and Safety Alerts Daily Med - Posting of Recently Submitted Labeling to the FDA
Starting date: February 2009
Last updated: June 6, 2011
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