Drug-Drug Interaction Study Between Colchicine and Ketoconazole
Condition: Pharmacokinetics
Study type: Interventional
Phase: Phase 1

Summary: 
      Ketoconazole is a potent 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 doses of ketoconazole 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: 
      Ketoconazole is a potent 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 doses of ketoconazole 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. 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 years
      will be given one dose of colchicine (1 x 0.6 mg tablet) orally on Day 1. Fasting will
      continue for 4 hours after the dose. Blood samples will be drawn from all participants before
      dosing and for twenty-four 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. On Days 15-18, subjects will return to the clinic daily for
      non-confined dosing of ketoconazole (1 x 200 mg tablet) twice daily, every 12 hours.
      Administered ketoconazole doses on these days will not necessarily be in a fasted state. On
      Day 15, after taking the first dose of ketoconazole, subjects will remain in the clinic for
      observation for 1 hour post-dose administration. Then, on Day 19, co-administration of a
      single dose of colchicine (1 x 0.6 mg tablet) and ketoconazole (1 x 200 mg tablet) will occur
      following a fast of at least 10 hours in subjects confined to the clinic for dosing and
      24-hour blood sampling will be performed at times sufficient to adequately determine the
      pharmacokinetics of colchicine. Blood sampling will continue on a non-confined basis on Days
      20-23. Fasting will continue for 4 hours following the co-administered dose of ketoconazole
      and colchicine. The final dose of ketoconazole (1 x 200 mg tablet) will be administered to
      subjects the evening of Day 19, in a non-fasting state. 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 19 to coincide with peak
      plasma concentrations of both colchicine and ketoconazole. 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.
    

Intervention name(s): Colchicine; Ketoconazole; Colchicine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): A single dose of colchicine 0.6 mg administered alone at 7:30 a.m. on Day 1.; one 200 mg Ketoconazole tablet administered twice daily at 7:15 a.m. and 7:15 p.m. on Days 15-18 without regard to meals, then along with colchicine at 7:15 a.m. on Day 19 after an overnight fast of at least 10 hours; final dose of 200 mg administered at 7:15 p.m. on Day 19; A single dose of colchicine 0.6 mg administered along with ketoconazole at 7:15 a.m. on Day 19 after an overnight fast of at least 10 hours
Other intervention name(s): COLCRYS TM
Intervention MeSH terms: Ketoconazole; Colchicine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: blood levels over time;; pharmacokinetics;; healthy adult;; cytochrome p450