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

Summary: 
      Colchicine is a supressor of hepatic CYP1A2 and theophylline is a sensitive CYP1A2 probe
      substrate. When the two are co-administered the potential exists for a clinically significant
      drug interaction. This study aims to determine the effect of steady-state colchicine on the
      pharmacokinetics of theophylline administered as a single dose. A secondary goal is to
      evaluate the safety and tolerability of this regimen in healthy volunteers. All study
      subjects will be monitored for adverse events throughout the entire study period.
    

Detailed description: 
      Colchicine is a supressor of hepatic CYP1A2 and theophylline is a sensitive CYP1A2 probe
      substrate. When the two are co-administered the potential exists for a clinically significant
      drug interaction . This study aims to determine the effect of steady-state colchicine on the
      pharmacokinetics of theophylline administered as a single dose. After a fast of at least 10
      hours, thirty healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages
      of 18 and 45 will be given one dose of 300mg (80mg/15ml concentrate) theophylline
      (theophylline elixir) on Day 1. 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 determine the pharmacokinetics of
      theophylline. Blood sampling will then continue on a non-confined basis on days 2-3. A four
      day washout period will be completed after the theophylline dose on Day 1 and prior to
      administration of the first colchicine dose on Day 5. Participants will return to the clinic
      on days 5-18 for non-confined dosing of colchicine (0.6mg every 12 hours). Administered
      dosing on these days will not necessarily be in a fasted state.

      On Day 19 after a fast of at least 10 hours, all study participants will receive 300mg
      theophylline (80mg/15ml) and 0.6 mg colchicine (1 x 0.6mg tablet) together. Fasting will
      continue for 4 hours following these co-administered doses. All subjects will be confined to
      the clinic for dosing and the following 24-hour period. Blood samples will be drawn at times
      sufficient to adequately determine the pharmacokinetics of theophylline in the presence of
      colchicine at steady state. Blood sampling will continue on a non-confined basis on Days
      20-21. The final dose of colchicine (1x0.6mg) will be administered to subjects the evening of
      Day 19.

      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, 5 (after the morning dose) 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): Theophylline; Colchicine
Intervention type(s): Drug; Drug
Intervention description(s): single doses of 300 mg (80 mg/15 ml elixer) administered alone at 7:45 am on Day 1 and then along with colchicine at 7:45 am on Day 19; one 0.6 mg tablet twice daily at 7:45 am and 7:45 pm on Days 5 to 19
Other intervention name(s): Elixophyllin® Elixir (Theophylline Anhydrous) 80/15 ml concentrate
Intervention MeSH terms: Colchicine; Theophylline
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: healthy;; adult;; blood levels over time