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

Summary: 
      Azithromycin is a possible weak to moderate inhibitor of CYP3A4, one of the enzymes
      responsible for the metabolism of colchicine. This study will evaluate the effect of multiple
      doses of azithromycin 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: 
      Azithromycin is a possible weak to moderate inhibitor of CYP3A4, one of the enzymes
      responsible for the metabolism of colchicine. This study will evaluate the effect of multiple
      doses of azithromycin on the pharmacokinetic profile of a single 0.6 mg 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 0.6 mg. 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 on Days 2-5. After a 2 week washout
      period, beginning on Day 15 and continuing through day 18, subjects will return to the clinic
      daily for non-confined dosing of azithromycin given orally 2 x 250 mg tablets on Day 15
      followed by 1 x 250 mg tablet on Days 16-18. Administered azithromycin doses on these days
      will not necessarily be in a fasted state. On Day 15 after taking the first dose of
      azithromycin, subjects will remain in the clinic for observation for 1 hour post-dose
      administration. On Day 19, after a fast of at least 10 hours, all study subjects will receive
      a co-administered single dose of colchicine (0.6 mg) and azithromycin (1 x 250 mg tablet).
      All subjects will be confined to the clinic for the 24-hour period following the dose. Blood
      will be drawn at time sufficient to define the pharmacokinetics of colchicine in the presence
      of azithromycin 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. Seated blood pressure and
      pulse will be measured prior to dosing and at approximately 1, 2, and 3 hours following drug
      administration on Days 1 and 19. 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; Azithromycin; Colchicine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): A single dose of 0.6 mg colchicine administered alone at 7:30 am on Day 1; Two 250 mg azithromycin tablets administered at 7:30 am on Day 15, then one 250 mg tablet administered daily at 7:30 am on Days 16 to 19.; A single dose of 0.6 mg colchicine administered with azithromycin at 7:30 am on Day 19.
Other intervention name(s): COLCRYS™; Zithromax® Tablets USP, 250 mg; COLCRYS™
Intervention MeSH terms: Azithromycin; Colchicine
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: blood levels over time;; colchicine;; azithromycin;; healthy