Drug-Drug Interaction Between Colchicine and Ritonavir
Condition: Pharmacokinetics
Study type: Interventional
Phase: Phase 1

Summary: 
      Ritonavir is a potent inhibitor of CYP3A4, one of the enzymes responsible for the metabolism
      of colchicine. This study will evaluate the effect of multiple doses of ritonavir 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: 
      Ritonavir is a potent inhibitor of CYP3A4, one of the enzymes responsible for the metabolism
      of colchicine. This study will evaluate the effect of multiple doses of ritonavir 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. 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) on Day 1. 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 14 day washout
      period, on study Days 15-18, subjects will return to the clinic daily for non-confined dosing
      of ritonavir (1 x 100 mg capsule) every 12 hours. Administered ritonavir doses on these days
      will not necessarily be in a fasted state. On Day 15, after taking the first dose of
      ritonavir, 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, a single dose of colchicine (1 x
      0.6 mg tablet) and ritonavir (1 x 100 mg capsule) will be co-administered to all study
      participants. Fasting will continue for 4 hours following the co-administered doses of
      ritonavir and colchicine. All participants will be confined to the clinic for dosing and
      24-hour blood sampling at times sufficient to adequately determine the pharmacokinetics of
      colchicine. Blood sampling will continue on a non-confined basis on Days 20-23. The final
      dose of ritonavir (1 x 100 mg capsule) will be administered to subjects the evening of Day
      19, in a non-fasting state. 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 prior to dosing and at 1, 2, and 3 hours
      following drug administration on Days 1, 15 and 19 to coincide with peak plasma
      concentrations of both colchicine and ritonavir. 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; Ritonavir; Colchicine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): A single dose of colchicine 0.6 mg administered alone at 7:00 a.m. on Day 1 after an overnight fast of at least 10 hours.; One 100 mg ritonavir capsule administered twice daily at 7:00 a.m. and 7:00 p.m. on Days 15 to 18 without regard to meals, then along with colchicine at 7:00 a.m. on Day 19 after an overnight fast of at least 10 hours; final dose of 100 mg ritonavir administered at 7:00 p.m. on Day 19; A single dose of colchicine 0.6 mg administered along with ritonavir at 7:00 a.m. on Day 19
Other intervention name(s): COLCRYS™; Norvir® Capsules USP, 100 mg (Abbott Laboratories)
Intervention MeSH terms: Ritonavir; Colchicine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science