Bioavailability Study of Colcrys® Crushed and Sprinkled on Applesauce

A Pilot Bioavailability Study of Colcrys® Tablet 0.6 mg Versus Colcrys® Tablets 0.6 mg Crushed and Sprinkled on Applesauce Under Fasting Conditions

The purpose of this study is to evaluate and compare the relative bioavailability of a single 0.6 mg tablet of Colcrys® (colchicine, USP) when crushed and sprinkled on applesauce (1 tablespoon) relative to the same dose given as an intact tablet to healthy subjects following an overnight fast. A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the study period.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Colchicine 0.6 mg tablet; Drug: Colchicine 0.6 mg tablet

Detailed Description

The purpose of this study is to evaluate and compare the relative bioavailability of a single 0.6 mg tablet of Colcrys® (colchicine, USP) when crushed and sprinkled on applesauce (1 tablespoon) relative to the same dose given as an intact tablet to healthy subjects following an overnight fast. Sixteen healthy, non-smoking, non-obese, male and female volunteers between 18-55 years of age will be randomly assigned in a crossover fashion to receive each of two dosing regimens in sequence with a 14 day washout period between dosing periods. In each of the dosing periods, after an overnight fast, subjects will receive one intact Colcrys® 0.6 mg tablet (followed by 240 mL of water) or one Colcrys® 0.6 mg tablet crushed and sprinkled on 1 tablespoon of applesauce (followed by 240 ml of water) according to the randomization schedule. Blood samples will be drawn from all participants before dosing and for 48 hours post-dose at times sufficient to adequately define the pharmacokinetics of colchicine. Vital signs (blood pressure, heart rate, respiratory rate and temperature) will be measured prior to dosing, 1 hour ± 30 minutes post-dose and upon discharge from the clinical facility. Subjects will be monitored throughout their participation in the study for adverse reactions.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89121
      • Novum Pharmaceutical Research Services

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 age 18-55, non-smoking, non- pregnant (post-menopausal, surgically sterile or using effective contraceptive measures) with a body mass index of 18-30 kg/m²

Exclusion Criteria:

• Recent participation (within 30 days) in other research studies
• Recent significant blood donation or plasma donation
• Pregnant or lactating
• Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV)
• History of treatment for drug or alcohol addiction within the previous 12 months or use of tobacco products within 90 days of the start of the study
• Significant history or current evidence of chronic infectious disease, system disorders, organ dysfunction, especially cardiovascular disorders (angina, heart failure, irregular heartbeats, heart attack, hypertension, hypotension) stroke, renal or hepatic disorders, diabetes or bleeding disorders, gastrointestinal disease or history of malabsorption within the last year
• History of psychiatric disorders occurring within the last two years that required hospitalization or medication
• Presence of a medical condition requiring regular treatment with prescription drugs
• Use of any drugs or substances known to inhibit or induce drug-metabolizing enzymes within 30 days prior to dosing with the study drug
• Drug allergies or sensitivity to colchicine
• Positive test results for drugs of abuse at screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colcrys® 0.6 mg intact tablet; One Colcrys® 0.6 mg intact tablet taken by mouth	Drug: Colchicine 0.6 mg tablet; One Colcrys® 0.6 mg intact tablet taken by mouth; Other Names: Colcrys®; Drug: Colchicine 0.6 mg tablet; One Colcrys® 0.6 mg tablet crushed and sprinkled on applesauce; Other Names: Colcrys®
Experimental: Colcrys® 0.6 mg tablet on applesauce; One Colcrys® 0.6 mg tablet crushed and sprinkled on applesauce	Drug: Colchicine 0.6 mg tablet; One Colcrys® 0.6 mg intact tablet taken by mouth; Other Names: Colcrys®; Drug: Colchicine 0.6 mg tablet; One Colcrys® 0.6 mg tablet crushed and sprinkled on applesauce; Other Names: Colcrys®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax)	The maximum or peak concentration that Colcrys® reaches in the plasma	serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 18, 20, 24, 36, and 48 hours after drug administration
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 Colcrys® plasma concentration to the elimination rate constant.	serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 18, 20, 24, 36, and 48 hours after drug administration
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 Colcrys® concentration (t), as calculated by the linear trapezoidal rule	serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 18, 20, 24, 36, and 48 hours after drug administration

Collaborators and Investigators

• Sponsor: Mutual Pharmaceutical Company, Inc.
• Investigators: Study Chair: Matthew Davis, M.D., Mutual Pharmaceutical Company, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: May 21, 2010
• First Submitted That Met QC Criteria: May 24, 2010
• First Posted (Estimate): May 25, 2010

Study Record Updates

• Last Update Posted (Estimate): May 12, 2011
• Last Update Submitted That Met QC Criteria: May 10, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: bioavailability
• Additional Relevant MeSH Terms: Wounds and Injuries; Crush Injuries; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: MPC-004-10-1002