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

Summary: 
      Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp).
      Verapamil hydrochloride is a potent inhibitor of cytochrome P450 (CYP) 3A4 and P-gp. This
      study will evaluate the effect of multiple doses of extended-release verapamil hydrochloride
      (verapamil HCl ER) 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).
      Verapamil hydrochloride is a potent inhibitor of cytochrome P450 (CYP) 3A4 and P-gp. This
      study will evaluate the effect of multiple doses of extended-release verapamil hydrochloride
      (verapamil HCl ER) 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 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. After a 14 day washout
      period, on Day 15 subjects will return to the clinic for dosing of verapamil HCl ER (1 x 240
      mg tablet) and a post-dose confinement period of 12 hours. Subjects will return on Days 16-19
      for a morning dose of verapamil HCl ER (1 x 240 mg tablet). Verapamil HCl ER doses
      administered on Days 15-18 will not necessarily be in a fasted state. On the morning of Day
      19 after a fast of at least 10 hours, all study participants will receive co-administered
      single doses of colchicine (1 x 0.6 mg) and verapamil HCl ER (1 x 240 mg). Fasting will
      continue for 4 hours following these doses and subjects will be confined to the clinic for
      dosing and for 24 hours after the dose. Blood samples will be drawn at times sufficient to
      adequately define the pharmacokinetics of colchicine in the presence of verapamil HCL at
      steady state. Blood sampling will continue on a non-confined basis on Days 20-23. 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 pre-dose and 1, 2, and 3 hours post-dose on Day 1, pre-dose and 12 hours post-dose
      on Day 15, and pre-dose and 1, 2 ,3 and 12 hours post-dose on Day 19 to coincide with peak
      plasma concentrations of both colchicine and verapamil HCl ER. 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; Verapamil HCl ER; Colchicine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): A single dose of 0.6 mg colchicine administered alone at 8am on Day 1 after an overnight fast of at least 10 hours.; One 240 mg verapamil HCl ER tablet taken at 8am on Days 15-18 without regard to meals and along with colchicine at 8am on Day 19 after an overnight fast of at least 10 hours.; A single dose of 0.6 mg colchicine administered along with verapamil HCL ER at 8 am on Day 19 after an overnight fast of at least 10 hours.
Intervention MeSH terms: Colchicine; Verapamil
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science