Clinical trial NCT00960193
Conditions: Healthy
Keywords: blood levels over time colchicine seville orange juice pharmacokinetics
Sponsor: Mutual Pharmaceutical Company, Inc.
Start date: 2009-02-01; Completion date: 2009-04-01
Enrollment: 24 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief 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.

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.

Arms: arm 1: baseline colchicine pharmacokinetics arm 2: colchicine pharmacokinetics in presence of Seville orange juice
Interventions: intervention 1: Colchicine intervention 2: Seville Orange Juice
Intervention descriptions: intervention 1: A single dose of 0.6 mg colchicine administered alone in the morning on Day 1 and a single dose of 0.6 mg colchicine administered with Seville orange juice in the morning on Day 18 after an overnight fast of at least 10 hours. intervention 2: 240 mL of Seville orange juice administered in the morning and evening on Days 15 to 18.

Protocol documents: