Drug-Drug Interaction Study Between Colchicine and Diltiazem ER
Condition: Healthy; Adult; Volunteer; Colchicine; Pharmacokinetics; Diltiazem; Cytochrome p450 3A4; P-glycoprotein
Study type: Interventional
Phase: Phase 1

Summary: 
      Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp).
      Extended-release diltiazem (diltiazem ER) is a potent inhibitor of both CYP3A4 and P-gp. This
      study will evaluate the effect of multiple doses of diltiazem 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).
      Extended-release diltiazem (diltiazem ER) is a potent inhibitor of both CYP3A4 and P-gp. This
      study will evaluate the effect of multiple doses of diltiazem ER on the pharmacokinetic
      profile of a single 0.6mg dose of colchicine. On 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 a single 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 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 at 36, 48, 72, and 96 hours post-dose. After a 14-day washout period,
      beginning on Day 15 and continuing through Day 20 all subjects will return to the clinic for
      non-confined dosing of diltiazem ER (1 x 240 mg capsule daily). Administered diltiazem ER
      doses on these days will not necessarily be in a fasted state. On Day 21 after a fast of at
      least 10 hours, all study participants will receive a co-administered single oral dose of
      colchicine (1 x 0.6 mg tablet) and diltiazem ER (1 x 240 mg capsule). 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 in the
      presence of diltiazem ER at steady state. Blood sampling will then continue on a non-confined
      basis at 36, 48, 72, and 96 hours post-dose administration. Fasting will continue for 4 hours
      following the co-administered dose of colchicine and diltiazem ER. 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 at 1, 2, and 3 hours post-dosing on Day 1, pre-dose and 12 hours post-dosing on
      Day 15 (subjects will return to the study center for the 12-hour post-dose vital sign
      measurements), and pre-dose and 1, 2, 3 and 12 hours post-dosing on Day 21 to coincide with
      peak plasma concentrations of both colchicine and diltiazem. 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; Diltiazem ER; Colchicine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): A single dose of 0.6 mg colchicine administered alone at 7:15 am on Day 1 after an overnight fast of at least 10 hours.; One 240 mg diltiazem ER capsule administered daily at 7:15 am on Days 15 to 21.; A single dose of 0.6 mg colchicine administered along with diltiazem ER at 7:15 am on Day 21 after an overnight fast of at least 10 hours.
Other intervention name(s): COLCRYS™; Cardizem® CD (Biovail Pharmaceuticals, Inc.)
Intervention MeSH terms: Colchicine; Diltiazem
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: healthy; adult; volunteer; colchicine; diltiazem; blood levels over time