Pharmacokinetics
Conditions
Keywords
healthy, blood levels
Brief summary
This study aims to characterize the pharmacokinetic profile of colchicine after a regimen of 1.8 mg over two hours. A secondary goal is to evaluate the safety and tolerability of this regimen in healthy volunteers. To this end, all study subjects will be monitored for adverse effects throughout the entire study period.
Detailed description
This study aims to characterize the pharmacokinetic profile of colchicine and its three main metabolites, after a regimen of 1.8 mg over two hours. After a fast of at least 10 hours, fifteen healthy non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 55 will be given colchicine 1.2 mg (2 x 0.6 mg) orally followed by an additional single 0.6mg dose one hour later. Fasting will continue for 4 hours after the first dose at which time a standardized meal will be served. Blood will be drawn from all participants at times sufficient to adequately define the pharmacokinetics of colchicine and its 3 major metabolites, 2, 3 and 10 demethylcolchicine. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. To this end, subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Seated and standing blood pressure and pulse will be measured prior to the first dose and 0.5, 1, 2, 4, and 12 hours post-dose. Twelve-lead electrocardiograms will be obtained at the same time points. All adverse events whether elicited by query, spontaneously reported, or observed by clinic staff will be evaluated by the Investigator and reported in the subject's case report form.
Interventions
colchicine 1.2mg initially; then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours)
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 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adults 18-55 years of age, non smoking and non-pregnant (postmenopausal, surgically sterile or using effective contraceptive measures) weighing at least 55kg and within 15% of ideal body weight.
Exclusion criteria
* Recent participation (within 30 days) in other research studies * Recent significant blood donation * Pregnant or lactating * Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) * Recent (2-year) history or evidence of alcoholism or drug abuse * History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease * Subjects who have used any drugs or substances known to inhibit or induce cytochrome (CYP) P450 enzymes and/or P-glycoprotein (P-gp) within 30 days prior to the first dose and throughout the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration | Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis). | The maximum or peak concentration that the drug reaches in the plasma. |
| Area Under the Concentration Time Curve From Time Zero to the Time of Last Measured Concentration (96 Hours) (AUC 0-t) | Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis). | The area under the plasma concentration versus time curve beginning from the first dose until the last quantifiable concentration (96hours), calculated by the linear trapezoidal rule. |
| Area Under The Concentration Time Curve From Zero Through Infinity (AUC∞) | Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis). | The area under the plasma concentration versus time curve extrapolated to infinity. AUC∞ is calculated as the sum of Total AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Electrocardiogram Corrected QT Interval (QTcF) | Measured at baseline, 0.5, 1, 2, and 4 hours | Corrected QT interval by Fridericia's formula -Measured at baseline, 0.5, 1, 2, and 4 hours |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Colchicine 1.2mg + 0.6mg On the morning of day one after a fast of at least 10 hours, all study participants received colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours) Blood was drawn at times sufficient to characterize the pharmacokinetics of Colchicine under this therapeutic regimen. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Oral Colchicine 1.2mg + 0.6mg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age Continuous | 28.9 years STANDARD_DEVIATION 8.4 |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / — |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Area Under the Concentration Time Curve From Time Zero to the Time of Last Measured Concentration (96 Hours) (AUC 0-t)
The area under the plasma concentration versus time curve beginning from the first dose until the last quantifiable concentration (96hours), calculated by the linear trapezoidal rule.
Time frame: Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Colchicine 1.2mg + 0.6mg | Area Under the Concentration Time Curve From Time Zero to the Time of Last Measured Concentration (96 Hours) (AUC 0-t) | 43787.55 pg-hr/ml | Standard Deviation 11437.48 |
Primary
Area Under The Concentration Time Curve From Zero Through Infinity (AUC∞)
The area under the plasma concentration versus time curve extrapolated to infinity. AUC∞ is calculated as the sum of Total AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant
Time frame: Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Colchicine 1.2mg + 0.6mg | Area Under The Concentration Time Curve From Zero Through Infinity (AUC∞) | 52070.06 pg-hr/ml | Standard Deviation 13689.27 |
Primary
Maximum Plasma Concentration
The maximum or peak concentration that the drug reaches in the plasma.
Time frame: Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Colchicine 1.2mg + 0.6mg | Maximum Plasma Concentration | 6192.77 picograms/ml | Standard Deviation 2433.7 |
Secondary
Electrocardiogram Corrected QT Interval (QTcF)
Corrected QT interval by Fridericia's formula -Measured at baseline, 0.5, 1, 2, and 4 hours
Time frame: Measured at baseline, 0.5, 1, 2, and 4 hours
Population: All participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Colchicine 1.2mg + 0.6mg | Electrocardiogram Corrected QT Interval (QTcF) | 402.28 Milliseconds | Standard Deviation 19.66 |
| Corrected QTc Interval (0.5 Hour) | Electrocardiogram Corrected QT Interval (QTcF) | 397.38 Milliseconds | Standard Deviation 18.37 |
| Corrected QTc Interval (1 Hour) | Electrocardiogram Corrected QT Interval (QTcF) | 399.26 Milliseconds | Standard Deviation 20.59 |
| Corrected QTc Interval (2 Hour) | Electrocardiogram Corrected QT Interval (QTcF) | 401.51 Milliseconds | Standard Deviation 20.64 |
| Corrected QTc Interval (4 Hour) | Electrocardiogram Corrected QT Interval (QTcF) | 402.38 Milliseconds | Standard Deviation 23.16 |