Bioavailability Study of Colcrys® Crushed and Sprinkled on Applesauce

• Maximum Plasma Concentration (Cmax) [ Time Frame: 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 ] [ Designated as safety issue: No ]
  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)] [ Time Frame: 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 ] [ Designated as safety issue: No ]
  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-∞)] [ Time Frame: 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 ] [ Designated as safety issue: No ]
  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.

• Maximum Plasma Concentration (Cmax) [ Time Frame: serial pharmacokinetic blood samples drawn prior to dosing (hour 0) and at multiple intervals after dosing ] [ Designated as safety issue: No ]
  The maximum or peak concentration that colchicine reaches in the plasma
• Area Under the Concentration Versus Time Curve from Time 0 to Time t [AUC(0-t)] [ Time Frame: serial pharmacokinetic blood samples drawn prior to dosing (hour 0) and at multiple intervals after dosing ] [ Designated as safety issue: No ]
  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
• Area Under the Concentration Versus Time Curve from Time 0 extrapolated to Infinity [AUC(0-∞)] [ Time Frame: serial pharmacokinetic blood samples drawn prior to dosing (hour 0) and at multiple intervals after dosing ] [ Designated as safety issue: No ]
  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.

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.

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.

• Drug: Colchicine 0.6 mg tablet
  One Colcrys® 0.6 mg intact tablet taken by mouth
  Other Name: Colcrys®
• Drug: Colchicine 0.6 mg tablet
  One Colcrys® 0.6 mg tablet crushed and sprinkled on applesauce
  Other Name: Colcrys®

• Experimental: Colcrys® 0.6 mg intact tablet
  One Colcrys® 0.6 mg intact tablet taken by mouth
  Intervention: Drug: Colchicine 0.6 mg tablet
• Experimental: Colcrys® 0.6 mg tablet on applesauce
  One Colcrys® 0.6 mg tablet crushed and sprinkled on applesauce
  Intervention: Drug: Colchicine 0.6 mg tablet

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