Drug-Drug Interaction Study Between Colchicine and Cyclosporine
Condition: Pharmacokinetics; Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp).
      Cyclosporine is a potent inhibitor of both CYP3A4 and P-gp. This study will evaluate the
      effect of single-dose cyclosporine 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 both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp).
      Cyclosporine is a potent inhibitor of both CYP3A4 and P-gp. This study will evaluate the
      effect of single-dose cyclosporine 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-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). 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 then continue on a non-confined basis on
      Days 2-5. A 14 day washout period will be completed after the first dose of colchicine on Day
      1. On Day 15 after a fast of at least 10 hours, all study participants will receive
      co-administered single oral doses of colchicine (1 x 0.6 mg tablet) and cyclosporine (1 x 100
      mg capsule). Fasting will continue for 4 hours after the dose. Subjects will be confined to
      the clinic for dosing and a 24 hour period after the dose. Blood samples will be drawn from
      all participants before dosing and during the 24 hour post-dose period at times sufficient to
      adequately determine the pharmacokinetics of colchicine. Blood sampling will continue on a
      non-confined basis on Days 16-19. 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 15 to coincide with peak plasma concentrations of
      both colchicine and cyclosporine. 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; Cyclosporine; Colchicine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): A single dose of 0.6 mg colchicine administered alone at 7:15 a.m. on Day 1 after an overnight fast of at least 10 hours.; A single dose of 100 mg cyclosporine administered with colchicine at 7:15 a.m. on Day 15 after an overnight fast of at least 10 hours.; A single dose of 0.6 mg colchicine administered with cyclosporine at 7:15 a.m. on Day 15 after an overnight fast of at least 10 hours.
Other intervention name(s): COLCRYS™; Neoral® (Novartis Pharmaceuticals Corporation)
Intervention MeSH terms: Cyclosporine; Colchicine; Cyclosporins
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: healthy; adult; colchicine; cyclosporine; blood levels over time