Bioequivalence Study of Colchicine Tablets

Study Overview
=================
Brief Summary
-----------------
This randomized, single dose, three-way crossover study will evaluate the bioequivalence of two formulations of colchicine, the test product (colchicine 0.6mg Mutual) and a marketed combination product (colchicine 0.5 mg with probenecid 500 mg), administered under fasting conditions. It will also determine the bioavailability following a standard high-fat meal and evaluate the safety and tolerability of the test product.

Detailed Description
-----------------
This randomized, single dose, three-way crossover study will evaluate the bioequivalence of two formulations of colchicine, the test product (colchicine 0.6mg Mutual) and a marketed combination product (colchicine 0.5mg with probenecid 500mg), administered under fasting conditions. It will also determine the bioavailability of the test product following a standard high-fat meal and evaluate the safety and tolerability of the test product. Twenty-eight healthy, non-smoking, non-obese (BMI 81-30 kg/m2 and BW ≥110 lbs), 18-45 year old, male and female volunteers will be randomly assigned in a crossover fashion to receive one of three dosing regimens in sequence with washout periods of at least 14 days between dosing periods. After a fast of at least 10 hours, subjects will receive either, one tablet of colchicine 0.6 mg, one tablet of colchicine 0.6 mg after a standardized high-fat,high-calorie breakfast or 0.5mg/500mg colchicine/probenecid. All doses will be given with 240mL of room temperature water. Patients will be confined for at least 15 hours before and 24 hours after each dose with daily outpatient visits over the following 3 days. Blood will be drawn at times sufficient to adequately define the concentration time curves for each dosing regimen, which will be compared to assess the bioequivalence of the reference and test products and the effect of food on the test product. Subjects will also be monitored for adverse events throughout this same period.

Official Title
-----------------
Randomized, 3-Way Crossover Bioequivalence Study of Single Dose Colchicine Tablets and Effect of Food

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Colchicine
* Drug: Colchicine
* Drug: Colchicine/Probenecid


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adult volunteers, male and female, 18 to 45 years of age, inclusive, with BMI between 18-30 kg/m2, inclusive, and weighing at least 110 pounds. Female volunteers must be postmenopausal, surgically sterile, or must commit to abstain from heterosexual contact or to use two methods of reliable birth control. Exclusion Criteria: Subjects who report receiving any investigational drug within 28 days prior to initiation of dosing. Subjects who report presence or history of significant cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, neurologic, or psychiatric disease. Subjects with clinical lab results outside accepted reference range, or reactive screen for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody. Subjects who report a history of allergies to colchicine or related drugs, or history of other clinically significant allergies including drug allergies. Subjects who report a clinically significant illness during the 4 weeks prior to initiation of dosing. Subjects who report a history of drug or alcohol addiction or abuse within the past year, or who demonstrate a positive drug abuse screen. Subjects who currently use or have used tobacco products within 6 months prior to dose administration. Subjects who report donating greater than 150 ml of blood within 28 days or donating plasma within 14 days prior to initiation of dosing. Subjects who have a positive pregnancy screen, or are currently pregnant or breastfeeding.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Colchicine (fasted) | Drug: Colchicine<br>* 0.6mg tablet administered after a fast of at least 10 hours<br>* Other names: COLCRYS TM;|
| Experimental: 2<br>Colchicine (fed) | Drug: Colchicine<br>* 0.6mg tablet administered after a standardized high-fat, high-calorie breakfast<br>* Other names: COLCRYS TM;|
| Active Comparator: 3<br>Colchicine/Probenecid (fasted) | Drug: Colchicine/Probenecid<br>* 0.5mg/500mg tablet administered after a fast of at least 10 hours<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Plasma Concentration (Cmax) | The maximum or peak concentration that colchicine reaches in the plasma. | serial pharmacokinetic blood samples collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 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 colchicine concentration (t), as calculated by the linear trapezoidal rule. | serial pharmacokinetic blood samples collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 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 colchicine plasma concentration to the elimination rate constant. | serial pharmacokinetic blood samples collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bioequivalence, fasting, fed, healthy