Pharmacokinetics
Conditions
Keywords
healthy, pharmacokinetics
Brief summary
This open label, single group, sequential dose study will compare the single dose pharmacokinetics of colchicine 0.6 mg given orally to colchicine pharmacokinetics after 10 days of a standard prophylactic dose (0.6 mg every 12 hours) in healthy volunteers.
Detailed description
This open label, single group, sequential dose study will compare the single dose pharmacokinetics of colchicine 0.6 mg given orally to colchicine pharmacokinetics after 10 days of a standard prophylactic dose (0.6 mg every 12 hours) in healthy volunteers. After a fast of at least 10 hours, fourteen healthy non-smoking, non-obese, non-pregnant volunteers will receive a single oral dose of colchicine 0.6 mg. Fasting will continue for 4 hours after the dose, at which time a standard meal will be served. Blood will be drawn from all participants at times sufficient to adequately define the single dose pharmacokinetics of colchicine and its 3 major metabolites, 2, 3 and 10 demethylcolchicine. Following a 14 day washout period, all participants will begin a 10 day regimen of colchicine 0.6 mg orally every 12 hours. On the morning of day 25, after a fast of at least 10 hours, all participants will receive their final dose of colchicine 0.6 mg. Again blood will be drawn at times sufficient to determine the pharmacokinetics of colchicine and its 3 major metabolites after chronic dosing. The pharmacokinetic parameters for each dosing situation will be derived and compared for relevant differences. Though not a specific goal of this study, all participants will be monitored for adverse events by observation and query during periods of confinement on days 1, 15 and 25, as well as by complete blood count (CBC) with differential and clinical chemistry, sitting and standing blood pressures, and heart rate and 12-lead electrocardiogram (EKG) before and after dosing, on days 1 and 25.
Interventions
0.6mg colchicine tablet
Sponsors
Mutual Pharmaceutical Company, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Completion of the screening process within 28 days prior to Period I dosing * Healthy non-smoking, non-obese adult men and women volunteers between the ages of 18 to 45 years of age, weighing at least 110 with a body mass index of 18-30kg/m2 * Women must be postmenopausal, surgically sterile, commit to abstinence from heterosexual sexual contact or use two methods of contraception.
Exclusion criteria
* Pregnant or lactating * Use of any investigational drug within 28 days prior to Period I dosing. * Presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease as determined by the clinical investigator(s) * Positive screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) * Clinical laboratory test values outside the accepted reference range and when confirmed on re-examination. * Any clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators) * Use of any systemic prescription medication in the 14 days prior to Period I dosing * History of any allergy(s) including allergy to colchicine or related drugs. * History of drug or alcohol addiction or abuse within the past year or a positive drug abuse screen * Currently or recent (within 6 months) use of tobacco products prior to dose administration * Donation of greater than 150 mL of blood within 28 days or plasma within 14 days prior to period I dosing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) | Pharmacokinetic samples collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing | maximum serum concentration measured after a single oral dose in fasted healthy adults and after a single oral dose in fasted healthy adults at steady state for comparison of the two conditions |
| Area Under the Concentration Versus Time Curve From Time Zero to the Time of the Last Measured Level. | 0.0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 36, 48, 72, and 96 hours after dosing | Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (t), calculated using the linear trapezoidal rule. |
| Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-inf) | 0.0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing | 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 plasma concentration to the elimination rate constant. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Colchicine - Single Dose, Twice Daily Dose, Final Single Dose All subjects received a single dose of colchicine 0.6 mg on Day 1 following an overnight fast. After a 14-day washout period, subjects received colchicine 0.6 mg every 12 hours for 10 days. On the morning of Day 25, subjects received their final colchicine 0.6 mg dose following an overnight fast. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Colchicine - Single Dose, Twice Daily Dose, Final Single Dose |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age Continuous | 25.5 years |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / — | 4 / — |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
Area Under the Concentration Versus Time Curve From Time Zero to the Time of the Last Measured Level.
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (t), calculated using the linear trapezoidal rule.
Time frame: 0.0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 36, 48, 72, and 96 hours after dosing
Population: by protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Colchicine Pharmacokinetics (Day 1) | Area Under the Concentration Versus Time Curve From Time Zero to the Time of the Last Measured Level. | 10494.66 pg-h/ml | Standard Deviation 3544.08 |
| Colchicine Pharmacokinetics at Steady State (Day 25) | Area Under the Concentration Versus Time Curve From Time Zero to the Time of the Last Measured Level. | 43576.96 pg-h/ml | Standard Deviation 9333.26 |
Primary
Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-inf)
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 plasma concentration to the elimination rate constant.
Time frame: 0.0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing
Population: by protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Colchicine Pharmacokinetics (Day 1) | Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-inf) | 12268.18 pg-h/ml | Standard Deviation 4422.08 |
| Colchicine Pharmacokinetics at Steady State (Day 25) | Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-inf) | 54198.77 pg-h/ml | Standard Deviation 9214.54 |
Primary
Maximum Serum Concentration (Cmax)
maximum serum concentration measured after a single oral dose in fasted healthy adults and after a single oral dose in fasted healthy adults at steady state for comparison of the two conditions
Time frame: Pharmacokinetic samples collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing
Population: per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Colchicine Pharmacokinetics (Day 1) | Maximum Serum Concentration (Cmax) | 2450.15 pg/mL | Standard Deviation 702.11 |
| Colchicine Pharmacokinetics at Steady State (Day 25) | Maximum Serum Concentration (Cmax) | 3553.15 pg/mL | Standard Deviation 843.45 |