Drug-Drug Interaction Study of Colchicine and Clarithromycin
Condition: Pharmacokinetics
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      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 open-label, one sequence,
      two-period, drug-drug interaction study will evaluate the effect of clarithromycin-related
      inhibition of CYP 3A4 and P-gp on colchicine pharmacokinetics in 24 healthy, non-smoking,
      non-obese (within +/- 15% of ideal body weight), male and female adult volunteers. The safety
      and tolerability of concurrent administration of clarithromycin and a single dose of
      colchicine will also be evaluated. During the first period, subjects will be confined to the
      study unit beginning the afternoon of the day prior to scheduled dosing (Day -1). On the
      morning of Day 1, after an overnight fast of at least 10 hours, subjects will be administered
      a single dose of colchicine 0.6 mg tablet with 240 ml of room temperature water. Blood will
      be drawn at times sufficient to characterize the baseline pharmacokinetics for this group.
      Following a 20 day washout period on Day 22, all subjects will return to the clinic to
      receive a supply of clarithromycin 250 mg tablets, which they will take on an outpatient
      basis twice daily (at 8 a.m. and 8 p.m.) without regard to meals for a total of 14 doses.
      Clinic staff will make telephone contact daily with subjects during this course to confirm
      compliance with the clarithromycin dosing regimen, and to monitor for adverse events and use
      of concomitant medication. On day 28 in the afternoon, subjects will again be confined to the
      study unit. On the morning of day 29, after an overnight fast of at least 10 hours all
      subjects will be administered a single dose of colchicine 0.6 mg and the final dose of
      clarithromycin with 240 ml water. Blood samples will be drawn at times sufficient to
      determine pharmacokinetic profiles of colchicine in the presence of clarithromycin at steady
      state. The pharmacokinetic profiles will be compared to determine the extent of drug-drug
      interaction.
    

Intervention name(s): colchicine; clarithromycin; colchicine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: healthy; pharmacokinetics; drug-drug interaction