Pharmacokinetic Study of an Acute Gout Regimen

Open-Label Pharmacokinetic Study of a Low-Dose Acute Gout Regimen

This study aims to characterize the pharmacokinetic profile of colchicine after a regimen of 1.8 mg over two hours. A secondary goal is to evaluate the safety and tolerability of this regimen in healthy volunteers. To this end, all study subjects will be monitored for adverse effects throughout the entire study period.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: colchicine tablets

Detailed Description

This study aims to characterize the pharmacokinetic profile of colchicine and its three main metabolites, after a regimen of 1.8 mg over two hours. After a fast of at least 10 hours, fifteen healthy non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 55 will be given colchicine 1.2 mg (2 x 0.6 mg) orally followed by an additional single 0.6mg dose one hour later. 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 and its 3 major metabolites, 2, 3 and 10 demethylcolchicine. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. To this end, subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Seated and standing blood pressure and pulse will be measured prior to the first dose and 0.5, 1, 2, 4, and 12 hours post-dose. Twelve-lead electrocardiograms will be obtained at the same time points. All adverse events whether elicited by query, spontaneously reported, or observed by clinic staff will be evaluated by the Investigator and reported in the subject's case report form.

• Study Type: Interventional
• Enrollment (Actual): 13
• 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: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adults 18-55 years of age, non smoking and non-pregnant (postmenopausal, surgically sterile or using effective contraceptive measures) weighing at least 55kg and within 15% of ideal body weight.

Exclusion Criteria:

• Recent participation (within 30 days) in other research studies
• Recent significant blood donation
• 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
• 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: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: colchicine; colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours)	Drug: colchicine tablets; colchicine 1.2mg initially; then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours); Other Names: COLCRYS TM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration	The maximum or peak concentration that the drug reaches in the plasma.	Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis).
Area Under the Concentration Time Curve From Time Zero to the Time of Last Measured Concentration (96 Hours) (AUC 0-t)	The area under the plasma concentration versus time curve beginning from the first dose until the last quantifiable concentration (96hours), calculated by the linear trapezoidal rule.	Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis).
Area Under The Concentration Time Curve From Zero Through Infinity (AUC∞)	The area under the plasma concentration versus time curve extrapolated to infinity. AUC∞ is calculated as the sum of Total AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant	Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrocardiogram Corrected QT Interval (QTcF)	Corrected QT interval by Fridericia's formula -Measured at baseline, 0.5, 1, 2, and 4 hours	Measured at baseline, 0.5, 1, 2, and 4 hours

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: September 1, 2007
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: August 12, 2009
• First Submitted That Met QC Criteria: October 5, 2009
• First Posted (Estimate): November 20, 2009

Study Record Updates

• Last Update Posted (Estimate): November 20, 2009
• Last Update Submitted That Met QC Criteria: October 5, 2009
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: healthy; blood levels
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: MPC-004-07-1003