Pharmacokinetic Study With Colchicine in Healthy Volunteers

Study Overview
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Brief Summary
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This open label, single group, sequential dose study will compare the single dose pharmacokinetics of colchicine 0.6 mg given orally to colchicine pharmacokinetics after 10 days of a standard prophylactic dose (0.6 mg every 12 hours) in healthy volunteers.

Detailed Description
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This open label, single group, sequential dose study will compare the single dose pharmacokinetics of colchicine 0.6 mg given orally to colchicine pharmacokinetics after 10 days of a standard prophylactic dose (0.6 mg every 12 hours) in healthy volunteers. After a fast of at least 10 hours, fourteen healthy non-smoking, non-obese, non-pregnant volunteers will receive a single oral dose of colchicine 0.6 mg. Fasting will continue for 4 hours after the dose, at which time a standard meal will be served. Blood will be drawn from all participants at times sufficient to adequately define the single dose pharmacokinetics of colchicine and its 3 major metabolites, 2, 3 and 10 demethylcolchicine. Following a 14 day washout period, all participants will begin a 10 day regimen of colchicine 0.6 mg orally every 12 hours. On the morning of day 25, after a fast of at least 10 hours, all participants will receive their final dose of colchicine 0.6 mg. Again blood will be drawn at times sufficient to determine the pharmacokinetics of colchicine and its 3 major metabolites after chronic dosing. The pharmacokinetic parameters for each dosing situation will be derived and compared for relevant differences. Though not a specific goal of this study, all participants will be monitored for adverse events by observation and query during periods of confinement on days 1, 15 and 25, as well as by complete blood count (CBC) with differential and clinical chemistry, sitting and standing blood pressures, and heart rate and 12-lead electrocardiogram (EKG) before and after dosing, on days 1 and 25.

Official Title
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An Open Label, Two Period, Sequential, Single Dose and Multiple Dose Pharmacokinetic Study With 0.6mg Colchicine Tablets in Healthy Volunteers

Conditions
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Pharmacokinetics

Intervention / Treatment
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* Drug: colchicine tablets
* Drug: colchicine tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completion of the screening process within 28 days prior to Period I dosing Healthy non-smoking, non-obese adult men and women volunteers between the ages of 18 to 45 years of age, weighing at least 110 with a body mass index of 18-30kg/m2 Women must be postmenopausal, surgically sterile, commit to abstinence from heterosexual sexual contact or use two methods of contraception. Exclusion Criteria: Pregnant or lactating Use of any investigational drug within 28 days prior to Period I dosing. Presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease as determined by the clinical investigator(s) Positive screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) Clinical laboratory test values outside the accepted reference range and when confirmed on re-examination. Any clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators) Use of any systemic prescription medication in the 14 days prior to Period I dosing History of any allergy(s) including allergy to colchicine or related drugs. History of drug or alcohol addiction or abuse within the past year or a positive drug abuse screen Currently or recent (within 6 months) use of tobacco products prior to dose administration Donation of greater than 150 mL of blood within 28 days or plasma within 14 days prior to period I dosing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>0.6mg colchicine tablet | Drug: colchicine tablets<br>* 0.6mg colchicine tablet<br>* Other names: COLCRYS TM;|
| Experimental: 2<br>colchicine 0.6mg q12 hours for 10 days | Drug: colchicine tablets<br>* 0.6mg q12 hours for 10 days<br>* Other names: COLCRYS TM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Serum Concentration (Cmax) | maximum serum concentration measured after a single oral dose in fasted healthy adults and after a single oral dose in fasted healthy adults at steady state for comparison of the two conditions | Pharmacokinetic samples collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing | 
| Area Under the Concentration Versus Time Curve From Time Zero to the Time of the Last Measured Level. | Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (t), calculated using the linear trapezoidal rule. | 0.0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 36, 48, 72, and 96 hours after dosing | 
| Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-inf) | 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. | 0.0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy, pharmacokinetics