Pharmacokinetic and Exploratory Electrocardiogram (ECG) Study

A Randomized, Double-Blind, Double-Dummy Pharmacokinetic and Exploratory Electrocardiogram (ECG) Safety Study of a Standard Acute Gout Regimen

This study will characterize the pharmacokinetics of colchicine after an oral dosing regimen of 4.8 mg over 6 hours. In addition it will compare the electrocardiogram (ECG) changes, if any, from this dosing regimen to that of a single dose of moxifloxacin 400 mg, a positive control for the corrected QT interval (QTc) prolongation.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: Colchicine; Drug: Moxifloxacin

Detailed Description

This study will characterize the pharmacokinetics of colchicine after an oral dosing regimen of 4.8 mg over 6 hours. In addition, it will determine whether or not there is a trend toward effect of this high dose regimen on the electrocardiogram (ECG), mainly the corrected QT interval (QTc), via comparison to a 400 mg dose of moxifloxacin, a positive control for QTc prolongation. Eighteen healthy, non-smoking, non-obese, non-pregnant adults between the ages of 18 to 55 years of age will be randomized in a double blind fashion to either the colchicine or moxifloxacin treatment groups. On the day prior to the study (Day -1), subjects will receive colchicine and moxifloxacin placebos according to the same schedule and conditions as will be present during the study, and baseline ECG's will be determined by 24 hour 12-lead Holter monitoring. On Day 1, after a minimum 10 hour overnight fast, subjects enrolled in the colchicine treatment group (N=15) will receive two 0.6 mg capsules (plus one dose moxifloxacin placebo) followed by an additional 0.6 mg colchicine dose (plus one dose moxifloxacin placebo) every hour for 6 additional doses; subjects in the moxifloxacin treatment group will receive placebo doses matching the colchicine treatment group over the first 5 hours, then 400 mg moxifloxacin (plus one dose colchicine placebo) at the 6 hour point. Fasting will continue for 4 hours after the first dose at which time a standardized meal will be served. Blood will be drawn from all participants at times sufficient to adequately define the pharmacokinetics of colchicine. During the study, continuous 24-hour ECG monitoring via 12-lead Holter monitor will be performed. Triplicate ECG records will be extracted from 5 minute observation periods throughout the 24 hours post dose. Finally, all study subjects will be monitored for adverse effects throughout the entire study period.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • PRACS Institute, Ltd. - Cetero Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adults 18-55 years of age, non smoking and non-pregnant, weighing at least 55kg and within 15% of ideal body weight, with no significant EKG changes

Exclusion Criteria:

• Pregnant or lactating
• Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV)
• Recent (2-year) history or evidence of alcoholism or drug abuse
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease
• History or family history of congenital long QT syndrome (LQTS) or sudden death possibly related to LQTS
• Subjects who have used any drugs or substances known to inhibit or induce cytochrome (CYP) P450 enzymes and/or P-glycoprotein (P-gp) within 30 days prior to the first dose and throughout the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colchicine	Drug: Colchicine; two 0.6 mg capsules (1.2 mg dose) followed by an additional 0.6mg capsule every hour for 6 additional doses; Other Names: COLCRYS TM
Active Comparator: Moxifloxacin	Drug: Moxifloxacin; 400 mg capsule at the 6 hour point

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax)	The maximum or peak concentration that colchicine reaches in the plasma.	serial pharmacokinetic blood samples collected pre-dose and 1 (prior to second dose), 3 (prior to fourth dose), 6 (prior to final dose), 6.17, 6.33, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 10, 12, 23, 36, 48, 72 and 96 hours post-dose
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]	The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable concentration (t), as calculated by the linear trapezoidal rule.	serial pharmacokinetic blood samples collected pre-dose and 1 (prior to second dose), 3 (prior to fourth dose), 6 (prior to final dose), 6.17, 6.33, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 10, 12, 23, 36, 48, 72 and 96 hours post-dose
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]	The area under the plasma concentration versus time curve from time 0 to infinity. AUC(0-∞) was calculated as the sum of AUC(0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant.	serial pharmacokinetic blood samples collected pre-dose and 1 (prior to second dose), 3 (prior to fourth dose), 6 (prior to final dose), 6.17, 6.33, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 10, 12, 23, 36, 48, 72 and 96 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrocardiogram (ECG) Evaluation of the QTcF Interval (Colchicine)	The QT interval assesses cardiac repolarization and risk for arrhythmias. It is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. It is dependent on heart rate and is corrected (c) to aid interpretation via Fridericia's adjustment (F), and is reported as QTcF.	24 hours - measured 0.5 hr prior to first dose (baseline), then 1, 3, 6, 7, 8, 10, 12, and 23 hours after first dose
Electrocardiogram (ECG) Evaluation of the QTcF Interval (Moxifloxacin)	The QT interval assesses cardiac repolarization and risk for arrhythmias. It is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. It is dependent on heart rate and is corrected (c) to aid interpretation via Fridericia's adjustment (F), and is reported as QTcF.	24 hours - measured 0.5 hr prior to dose (baseline), then 1, 3, 6, 7, 8, 10, 12, and 23 hours after dose

Collaborators and Investigators

• Sponsor: Mutual Pharmaceutical Company, Inc.
• Investigators: Principal Investigator: Anthony R Godfrey, Pharm.D., PRACS Institiute, Ltd.

Publications and helpful links

Helpful Links

• Recalls, Market Withdrawals and Safety Alerts
• Daily Med - Posting of Recently Submitted Labeling to the FDA

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: August 12, 2009
• First Submitted That Met QC Criteria: October 5, 2009
• First Posted (Estimate): November 23, 2009

Study Record Updates

• Last Update Posted (Estimate): December 1, 2009
• Last Update Submitted That Met QC Criteria: November 24, 2009
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: healthy
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Gout Suppressants; Moxifloxacin; Colchicine
• Other Study ID Numbers: MPC-004-07-1002