Drug-Drug Interaction Study of Colchicine and Clarithromycin
Condition: Pharmacokinetics
Intervention: colchicine; clarithromycin; colchicine
Intervention description: 0.6mg tablet administered at 9am on Day 1; 250 mg clarithromycin tablet taken on an outpatient basis twice daily at 8am and 8pm for 14 doses (starting with 8pm dose on Day 22 and concluding with 8am dose on Day 29); 0.6 mg tablet administered at 9am on Day 29
Intervention MeSH terms: Clarithromycin; Colchicine
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: healthy; pharmacokinetics; drug-drug interaction

Summary:

      Clarithromycin is a potent inhibitor of the activity of cytochrome P450 (CYP) 3A4 and
      P-glycoprotein (P-gp). CYP 3A4 plays a role in the metabolism of colchicine and P-gp is
      responsible for the efflux of colchicine across membranes. This study will evaluate the
      effect of clarithromycin-related inhibition of CYP 3A4 and P-gp on the pharmacokinetics of
      colchicine. It will also evaluate the safety and tolerability of concurrent administration of
      clarithromycin and a single dose of colchicine.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy, non-smoking, adult volunteers, male and female, 18 to 45 years of age,
             weighing at least 55 kg and within 15% of ideal body weight, with hemoglobin >/=12
             g/dL.

          -  Female volunteers must be sexually abstinent for 14 days prior to the first dose and
             throughout the study or using acceptable birth control methods (prior to and during
             the study), including being postmenopausal or surgically sterile (or sexual activity
             restricted to a partner that is surgically sterile), hormonal contraception, an IUD,
             or barrier methods with spermicide. Additionally, they will be advised to remain
             sexually inactive or to keep the same birth control method for at least 14 days
             following the last dose of colchicine.

        Exclusion Criteria:

          -  Subjects who are pregnant or lactating

          -  Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface
             antigen (HbsAg) or hepatitis C virus (HCV)

          -  Have history or presence of significant cardiovascular, pulmonary, hepatic, renal,
             hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or
             psychiatric disease; have used any drugs or substances known to inhibit or induce CYP
             enzymes and/or P-gp within 30 days prior to the first dose and throughout the study

          -  Recent (2-year) history of evidence of alcoholism or drug abuse

          -  Subjects who donated 50-499 ml of blood within 30 days and more than 499 ml within 56
             days prior to the first dose; subjects who have donated in excess of 500 ml of blood
             in 14 days, 1500 ml or blood in 180 days, or 2500 ml of blood in 1 year (through
             completion of the study)

          -  Have participated in another clinical trial within 30 days prior to dosing

          -  Known and documented drug allergies to colchicine or macrolide antibiotics.