Healthy
Conditions
Keywords
bioavailability
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 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.
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.
Interventions
One Colcrys® 0.6 mg intact tablet taken by mouth
Sponsors
Mutual Pharmaceutical Company, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Colcrys® Intact Tab and Colcrys® in Applesauce All subjects received each of the two study regimens in a randomly assigned sequence of dosing periods. On the mornings of Day 1 and Day 15, each subject received one tablet of intact Colcrys® 0.6 mg or one tablet of Colcrys® 0.6 mg crushed and sprinkled on applesauce, following an overnight fast of at least 10 hours. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Period of 14 Days | Protocol Violation | 1 | 1 |
| Washout Period of 14 Days | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Colcrys® Intact Tab and Colcrys® in Applesauce |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age Continuous | 37.812 years STANDARD_DEVIATION 13.332 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 14 | 1 / 15 |
| serious Total, serious adverse events | 0 / 14 | 0 / 15 |
Outcome results
Primary
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.
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
Population: Plasma concentration data for 13 of 16 participants were used in the statistical analysis. One subject dropped from the study before Period 2 dosing for personal reasons. Two subjects were discontinued from the study before Period 2 for protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Colcrys® 0.6 mg Administered as an Intact Tablet | Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] | 28.550 ng-hr/mL | Standard Deviation 8.597 |
| Colcrys® 0.6 mg Tablet Crushed and Sprinkled on Applesauce | Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] | 23.883 ng-hr/mL | Standard Deviation 6.102 |
Primary
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
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
Population: Plasma concentration data for 13 of 16 participants were used in the statistical analysis. One subject dropped from the study before Period 2 dosing for personal reasons. Two subjects were discontinued from the study before Period 2 for protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Colcrys® 0.6 mg Administered as an Intact Tablet | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 23.042 ng-hr/mL | Standard Deviation 6.1 |
| Colcrys® 0.6 mg Tablet Crushed and Sprinkled on Applesauce | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 19.216 ng-hr/mL | Standard Deviation 4.512 |
Primary
Maximum Plasma Concentration (Cmax)
The maximum or peak concentration that Colcrys® reaches in the plasma
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
Population: Plasma concentration data for 13 of 16 participants were used in the statistical analysis. One subject dropped from the study before Period 2 dosing for personal reasons. Two subjects were discontinued from the study before Period 2 for protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Colcrys® 0.6 mg Administered as an Intact Tablet | Maximum Plasma Concentration (Cmax) | 3.087 ng/mL | Standard Deviation 0.953 |
| Colcrys® 0.6 mg Tablet Crushed and Sprinkled on Applesauce | Maximum Plasma Concentration (Cmax) | 2.616 ng/mL | Standard Deviation 0.785 |