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

NCT ID: NCT01084278

Last Updated: 2012-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2011-02-28

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.

Conditions

Pharmacokinetics

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Healthy

Healthy participants with normal renal function (Creatinine Clearance \[CrCl\] ≥90 mL/min) received one colchicine 0.6 mg tablet on study day 1.

Group Type: EXPERIMENTAL

Colchicine

Intervention Type: DRUG

Colchicine tablets

Mild renal impairment

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.

Group Type: EXPERIMENTAL

Colchicine

Intervention Type: DRUG

Colchicine tablets

Moderate renal impairment

Participants with moderate renal impairment (CrCl/eGFR 30 to 59 mL/min) received one colchicine 0.6 mg tablet on study day 1.

Group Type: EXPERIMENTAL

Colchicine

Intervention Type: DRUG

Colchicine tablets

Severe renal impairment

Participants with severe renal impairment (eGFR 15 to 29 mL/min) received one colchicine 0.6 mg tablet on study day 1.

Group Type: EXPERIMENTAL

Colchicine

Intervention Type: DRUG

Colchicine tablets

End stage renal disease (ESRD)

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.

Group Type: EXPERIMENTAL

Colchicine

Intervention Type: DRUG

Colchicine tablets

Interventions

Colchicine

Colchicine tablets

Intervention Type: DRUG

Other Intervention Names

COLCRYS

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew Davis, MD

Role: STUDY_CHAIR

Mutual Pharmaceutical Company, Inc.

Javier T Quesada, DO

Role: PRINCIPAL_INVESTIGATOR

West Coast Clinical Trials, LLC

Locations

West Coast Clinical Trials

Cypress, California, United States

Countries

United States

Other Identifiers

U1111-1132-3386

Identifier Type: REGISTRY

Identifier Source: secondary_id

MPC-004-09-1028

Identifier Type: -

Identifier Source: org_study_id