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

NCT01084278 | Completed Phase 4 Results

• 2 other identifiers: MPC-004-09-1028U1111-1132-3386
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetics

Outcome Measures

Primary Outcomes (15)

• Maximum Plasma Concentration (Cmax)

  The maximum or peak concentration of colchicine in the plasma.

  Day 1 and Day 15 (for ESRD patients only) pre-dose and at 0.5, 1, 1.5 , 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 hours post dose

• Time to Maximum Plasma Concentration (Tmax)

  The time to reach the maximum or peak concentration of colchicine in the plasma.

  Day 1 and Day 15 (for ESRD patients only) at 0.5, 1, 1.5 , 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 hours post dose

• Area Under the Concentration Time Curve From Time Zero to the Time of Last Measured Concentration (AUC 0-t)

  The area under the plasma concentration versus time curve beginning from the first dose until the last quantifiable concentration, calculated by the linear trapezoidal method.

  Day 1 and Day 15 (ESRD patients only), predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post dose

• Area Under the Concentration Time Curve From Time Zero to Infinity (AUC 0 - ∞)

  The area under the plasma concentration versus time curve extrapolated to infinity. AUC 0 - ∞ is calculated as the sum of total AUC 0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant.

  Day 1 and Day 15 (for ESRD patients only) pre-dose and at 0.5, 1, 1.5 , 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 hours post dose.

• Apparent First-order Terminal Elimination Rate Constant (Kel)

  Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma concentration versus time curve for colchicine. The parameter was calculated by linear least-squares regression analysis using the maximum number of points in the terminal log-linear phase (e.g., three or more non-zero plasma concentrations).

  Day 1 and Day 15 (for ESRD patients only) pre-dose and at 0.5, 1, 1.5 , 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 hours post dose.

• Apparent First-order Terminal Elimination Half-life (t½)

  The apparent first-order terminal elimination half-life was calculated as 0.693/Kel.

  Day 1 and Day 15 (for ESRD patients only) pre-dose and at 0.5, 1, 1.5 , 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 hours post dose.

• The Apparent Total Volume of Distribution After Administration (V-area/F)

  The apparent total volume of distribution after administration of colchicine, calculated as Dose / (AUC0-∞ × Kel).

  Day 1 and Day 15 (for ESRD patients only) pre-dose and at 0.5, 1, 1.5 , 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 hours post dose.

• Weight-adjusted Apparent Total Volume of Distribution After Administration (V-area/F)

  The apparent total volume of distribution after administration of colchicine, calculated as Dose / (AUC0-∞ × Kel), and normalized to body weight.

  Day 1 and Day 15 (for ESRD patients only) pre-dose and at 0.5, 1, 1.5 , 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 hours post dose.

• Apparent Total Body Clearance of Colchicine

  The apparent total body clearance after administration of colchicine, calculated as Dose/AUC(0-∞).

  Day 1 and Day 15 (for ESRD patients only) pre-dose and at 0.5, 1, 1.5 , 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 hours post dose.

• Weight-adjusted Apparent Total Body Clearance of Colchicine

  The apparent total body clearance after administration of colchicine, calculated as Dose/AUC(0-∞) and normalized to body weight (in kilograms).

  Day 1 and Day 15 (for ESRD patients only) pre-dose and at 0.5, 1, 1.5 , 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 hours post dose.

• Amount of Colchicine Excreted in Urine (Ae[0-t])

  The amount of colchicine excreted in urine during the post-dose collection, calculated as the sum of the amounts in the individual collection intervals (Ae).

  Pre-dose on Day 1 and up to 120 hours post dose.

• Percentage of Colchicine Dose Excreted in Urine up to the Final Collection Time

  The cumulative percentage of the colchicine dose excreted in urine up to the final collection time, calculated as Ae(0-t) × 100/dose

  Pre-dose on Day 1 and up to 120 hours post dose.

• Renal Clearance of Colchicine (CLR)

  Renal clearance of colchicine, calculated as Ae(0 t)/AUC 0-t.

  Pre-dose on Day 1 and up to 120 hours post dose.

• Dialysis Clearance of Colchicine (CLD)

  The dialysis clearance of colchicine, calculated as amount of colchicine recovered in dialysate / AUCt2-t1 where t1 and t2 are the times of the start and end of hemodialysis.

  Day 15, post-dose during dialysis

• Percentage of Colchicine Dose Recovered in Dialysate

  The cumulative percentage of the colchicine dose recovered in dialysate.

  Day 15, post-dose during dialysis

Study Arms (5)

Healthy

EXPERIMENTAL

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

Drug: Colchicine

Mild renal impairment

EXPERIMENTAL

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.

Drug: Colchicine

Moderate renal impairment

EXPERIMENTAL

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

Drug: Colchicine

Severe renal impairment

EXPERIMENTAL

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

Drug: Colchicine

End stage renal disease (ESRD)

EXPERIMENTAL

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.

Drug: Colchicine

Interventions

Colchicine DRUG

Colchicine tablets

Also known as: COLCRYS

End stage renal disease (ESRD); Healthy; Mild renal impairment; Moderate renal impairment; Severe renal impairment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

West Coast Clinical Trials

Cypress, California, 90630, United States

Location

MeSH Terms

Interventions

Colchicine

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Sr. VP, Clinical Science
• Organization: Takeda Global Research and Development Center, Inc.

clinicaltrialregistry@tpna.com

800-778-2860

Study Officials

• Matthew Davis, MD

  Mutual Pharmaceutical Company, Inc.

  STUDY CHAIR

• Javier T Quesada, DO

  West Coast Clinical Trials, LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2010
• First Posted: March 10, 2010
• Study Start: May 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: October 12, 2012
• Results First Posted: October 12, 2012

Record last verified: 2012-09

Locations

US (1)