Healthy and Renal Impairment Study of Colcrys (Colchicine, USP)

Single-Dose, Open-Label Study of the Pharmacokinetics, Safety, and Tolerability of Colcrys (Colchicine, USP) Tablets 0.6 mg Administered to Healthy Subjects and Subjects With Mild, Moderate, Severe Renal Impairment, and End-Stage Renal Disease

The primary objective of this study is to compare the pharmacokinetic profiles of colchicine and its primary metabolites in plasma and urine following a single 0.6 mg oral dose of colchicine in healthy adults with normal renal function, in patients with mild, moderate or severe renal impairment, and in patients with end-stage renal disease on hemodialysis. An additional objective of this study is to study the clearance of colchicine and its metabolites by hemodialysis. Secondary objectives include evaluation of the safety and tolerability of colchicine in the study population.

40 male and female subjects will be enrolled in the study and stratified into one of five groups based on their renal status as determined from creatinine clearance (CrCL) estimated using the serum creatinine (sCR) and the Cockcroft-Gault and Modified Diet in Renal Disease (MDRD) equations as follows: Treatment group 1 - healthy adults with normal renal function (CrCL/eGFR> 90 mL/min); Treatment groups 2, 3 and 4 - patients with mild (CrCL/eGFR 60-89 mL/min), moderate (CrCL/eGFR 30 to 59 mL/min), and severe (CrCL/eGFR 15 to 29 mL/min) renal impairment, respectively; and Treatment group 5 - subjects with end-stage renal disease requiring hemodialysis. On study day 1, participants in Treatment Groups 1 to 4 will be administered one colchicine 0.6 mg tablet at 8 a.m. under standard fasting conditions. Blood samples will be collected from all participants before dosing and both blood and urine samples will be collected for 120 hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of colchicine and its primary metabolites. There will be two study periods for treatment group 5; Period 1 off dialysis and Period 2 on dialysis with a 14 day washout period between the two study periods. On study day 1, participants in treatment group 5 will be administered one colchicine 0.6 mg tablet under standard fasting conditions immediately following dialysis. Blood samples will be collected from all participants before dosing and for up to 70 hours post-dose at times sufficient to adequately determine the pharmacokinetics of colchicine and its primary metabolites. All adverse events will be evaluated by the investigator and reported in the participant's case report form.

Inclusion Criteria:

• Adult males and females 18-70 years old with a body mass index of <39 kg/m^2.
• Patients with normal renal function or mild renal impairment should be generally healthy on the basis of medical history and physical exam.
• Patients with moderate to end stage renal impairment should be generally medically healthy other than with respect to the morbidities associated with impaired renal function.
• Non-pregnant (post-menopausal, surgically sterile or using effective contraceptive measures).

Exclusion Criteria:

• Known hypersensitivity to colchicine or any component of the formulation of the study drug.
• Patients with a history or presence of a significant medical condition that would interfere with interpretation of the study results.
• Patients who have used any drugs or substances known to inhibit or induce cytochrome P450 (CYP) enzymes and/or P-glycoprotein within 28 days prior to the first dose and throughout the study.
• Patients with recent (2 year) history or evidence of alcoholism or drug abuse or significant psychiatric disease.
• Patients with chronic hepatic dysfunction.