Bioavailability Study of Colcrys® in Apple Juice

Phase 1

Completed

Brief Summary: 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 dissolved in apple juice relative to the same dose given as an intact tablet to healthy subjects following an overnight fast.

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 dissolved in apple juice 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 dissolved in 20 mL of apple juice (followed by 220 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 and at 1 hour ± 30 minutes post dose. Subjects will be monitored throughout their participation in the study for adverse reactions.

Recruitment & Eligibility

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 or 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

Arm && Interventions

Group	Intervention	Description
Colcrys® (colchicine USP) 0.6 mg intact tablet	colchicine 0.6 mg tablet	One Colcrys® (colchicine USP) 0.6 mg intact tablet taken by mouth
Colcrys® 0.6 mg tab in apple juice	colchicine 0.6 mg tablet	One Colcrys® 0.6 mg tablet crushed and dissolved in apple juice

Primary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration (Cmax)	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	The maximum or peak concentration that Colcrys® reaches in the plasma
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC (0-t)]	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	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
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]	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	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.