Drug-Drug Interaction Study Between Colchicine and Atorvastatin
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      Colchicine is a substrate for cytochrome P450 3A4 (CYP3A4). In-vitro studies have indicated
      that the ortho-and para-hydroxylated metabolites of atorvastatin may be CYP3A4/5 competitive
      and mechanism-based inhibitors (MBI). This study will evaluate the effect of multiple doses
      of atorvastatin 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: 
      Colchicine is a substrate for cytochrome P450 3A4 (CYP3A4). In-vitro studies have indicated
      that the ortho-and para-hydroxylated metabolites of atorvastatin may be CYP3A4 /5 competitive
      and mechanism-based inhibitors (MBI). This study will evaluate the effect of multiple doses
      of atorvastatin 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 oral dose of colchicine (1 x 0.6 mg tablet) on Day 1 after an
      overnight fast. Blood samples will be drawn from all participants before dosing and for 24
      hours post-dose at times sufficient to adequately define the pharmacokinetics of colchicine.
      After a 14 day washout period, starting on the morning of Day 15 and continuing through Day
      27, subjects will return to the clinic for once daily administration of atorvastatin (1 x 40
      mg tablet) after an overnight fast. After taking the first dose of atorvastatin on Day 15,
      subjects will remain in the clinic for 1 hour post-dose administration for observation. On
      the morning of Day 28 after an overnight fast, all study participants will receive a
      co-administered single oral dose of colchicine (1 x 0.6 mg tablet) and atorvastatin (1 x 40
      mg tablet). Blood samples will be drawn from all participants before dosing and for
      twenty-four hours post-dose at times sufficient to adequately define the pharmacokinetics of
      colchicine in the presence of atorvastatin at steady 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. Seated blood pressure and pulse, respiratory rate and temperature will be
      measured at screening, baseline and upon study discharge. Blood pressure and pulse will also
      be measured pre-dose and at 1 and 2 hours post-dose on Days 1 and 28 to coincide with peak
      plasma concentrations of colchicine and atorvastatin. 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; Atorvastatin; Colchicine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): A single dose of 0.6 mg colchicine administered alone in the morning on Day 1.; Atorvastatin (1 x 40 mg tablet) administered once daily on Days 15-28.; A single dose of 0.6 mg colchicine administered with a single dose of 40 mg atorvastatin in the morning on Day 28 after an overnight fast.
Intervention MeSH terms: Colchicine; Atorvastatin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: pharmacokinetics