Clinical trial NCT01084278
Conditions: Pharmacokinetics
Sponsor: Takeda
Start date: 2010-05-01; Completion date: 2011-02-01
Enrollment: 40 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: Healthy participants with normal renal function (Creatinine Clearance \[CrCl\] ≥90 mL/min) received one colchicine 0.6 mg tablet on study day 1. arm 2: Participants with mild renal impairment (estimated Glomerular Filtration Rate \[eGFR\] 60 to 89 mL/min) received one colchicine 0.6 mg tablet on study day 1. arm 3: Participants with moderate renal impairment (CrCl/eGFR 30 to 59 mL/min) received one colchicine 0.6 mg tablet on study day 1. arm 4: Participants with severe renal impairment (eGFR 15 to 29 mL/min) received one colchicine 0.6 mg tablet on study day 1. arm 5: Participants with end stage renal disease (ESRD) received one colchicine 0.6 mg tablet on study day 1 immediately following dialysis. After a 14-day washout, participants received one colchicine 0.6 mg tablet on Day 15 prior to dialysis.
Interventions: intervention 1: Colchicine
Intervention descriptions: intervention 1: Colchicine tablets

Protocol documents: