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This study will characterize the pharmacokinetics of colchicine after an oral dosing regimen of 4.8 mg over 6 hours. In addition it will compare the electrocardiogram (ECG) changes, if any, from this dosing regimen to that of a single dose of moxifloxacin 400 mg, a positive control for the corrected QT interval (QTc) prolongation.
This study will characterize the pharmacokinetics of colchicine after an oral dosing regimen of 4.8 mg over 6 hours. In addition, it will determine whether or not there is a trend toward effect of this high dose regimen on the electrocardiogram (ECG), mainly the corrected QT interval (QTc), via comparison to a 400 mg dose of moxifloxacin, a positive control for QTc prolongation. Eighteen healthy, non-smoking, non-obese, non-pregnant adults between the ages of 18 to 55 years of age will be randomized in a double blind fashion to either the colchicine or moxifloxacin treatment groups. On the day prior to the study (Day -1), subjects will receive colchicine and moxifloxacin placebos according to the same schedule and conditions as will be present during the study, and baseline ECG's will be determined by 24 hour 12-lead Holter monitoring. On Day 1, after a minimum 10 hour overnight fast, subjects enrolled in the colchicine treatment group (N=15) will receive two 0.6 mg capsules (plus one dose moxifloxacin placebo) followed by an additional 0.6 mg colchicine dose (plus one dose moxifloxacin placebo) every hour for 6 additional doses; subjects in the moxifloxacin treatment group will receive placebo doses matching the colchicine treatment group over the first 5 hours, then 400 mg moxifloxacin (plus one dose colchicine placebo) at the 6 hour point. 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. During the study, continuous 24-hour ECG monitoring via 12-lead Holter monitor will be performed. Triplicate ECG records will be extracted from 5 minute observation periods throughout the 24 hours post dose. Finally, all study subjects will be monitored for adverse effects throughout the entire study period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Colchicine | Experimental |
| |
| Moxifloxacin | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Colchicine | Drug | two 0.6 mg capsules (1.2 mg dose) followed by an additional 0.6mg capsule every hour for 6 additional doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | The maximum or peak concentration that colchicine reaches in the plasma. | serial pharmacokinetic blood samples collected pre-dose and 1 (prior to second dose), 3 (prior to fourth dose), 6 (prior to final dose), 6.17, 6.33, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 10, 12, 23, 36, 48, 72 and 96 hours post-dose |
| 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 concentration (t), as calculated by the linear trapezoidal rule. | serial pharmacokinetic blood samples collected pre-dose and 1 (prior to second dose), 3 (prior to fourth dose), 6 (prior to final dose), 6.17, 6.33, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 10, 12, 23, 36, 48, 72 and 96 hours post-dose |
| 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 plasma concentration to the elimination rate constant. | serial pharmacokinetic blood samples collected pre-dose and 1 (prior to second dose), 3 (prior to fourth dose), 6 (prior to final dose), 6.17, 6.33, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 10, 12, 23, 36, 48, 72 and 96 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Electrocardiogram (ECG) Evaluation of the QTcF Interval (Colchicine) | The QT interval assesses cardiac repolarization and risk for arrhythmias. It is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. It is dependent on heart rate and is corrected (c) to aid interpretation via Fridericia's adjustment (F), and is reported as QTcF. | 24 hours - measured 0.5 hr prior to first dose (baseline), then 1, 3, 6, 7, 8, 10, 12, and 23 hours after first dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anthony R Godfrey, Pharm.D. | PRACS Institiute, Ltd. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PRACS Institute, Ltd. - Cetero Research | Fargo | North Dakota | 58104 | United States |
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| Label | URL |
|---|---|
| Recalls, Market Withdrawals and Safety Alerts | View source |
| Daily Med - Posting of Recently Submitted Labeling to the FDA | View source |
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50 subjects screened, 28 were screen failures, 4 were alternates
Eighteen (18) healthy, non-smoking, adult male and female volunteers, consisting of university students and members of the community at large, were to be enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | Colchicine | 1.2mg initially (two 0.6 mg capsules) followed by an additional 0.6mg capsule every hour for 6 additional doses [4.8mg over 6 hours] |
| FG001 | Moxifloxacin | 400 mg capsule at the 6 hour point |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Colchicine | 1.2mg initially (two 0.6 mg capsules) followed by an additional 0.6mg capsule every hour for 6 additional doses [4.8mg over 6 hours] |
| BG001 | Moxifloxacin | 400 mg capsule at the 6 hour point |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | age range: >=18 and <=55 |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Plasma Concentration (Cmax) | The maximum or peak concentration that colchicine reaches in the plasma. | Posted | Mean | Standard Deviation | ng/mL | serial pharmacokinetic blood samples collected pre-dose and 1 (prior to second dose), 3 (prior to fourth dose), 6 (prior to final dose), 6.17, 6.33, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 10, 12, 23, 36, 48, 72 and 96 hours post-dose |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Colchicine | 1.2mg initially (two 0.6 mg capsules) followed by an additional 0.6mg capsule every hour for 6 additional doses [4.8mg over 6 hours] |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| diarrhoea | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Mutual Pharmaceutical Company, Inc. | 215-697-1743 | clinicaltrials@urlmutual.com |
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| ID | Term |
|---|---|
| D003078 | Colchicine |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
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| Moxifloxacin | Drug | 400 mg capsule at the 6 hour point |
|
| Electrocardiogram (ECG) Evaluation of the QTcF Interval (Moxifloxacin) | The QT interval assesses cardiac repolarization and risk for arrhythmias. It is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. It is dependent on heart rate and is corrected (c) to aid interpretation via Fridericia's adjustment (F), and is reported as QTcF. | 24 hours - measured 0.5 hr prior to dose (baseline), then 1, 3, 6, 7, 8, 10, 12, and 23 hours after dose |
| BG002 | Total | Total of all reporting groups |
| Count of Participants |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| 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 concentration (t), as calculated by the linear trapezoidal rule. | Posted | Mean | Standard Deviation | ng-hr/mL | serial pharmacokinetic blood samples collected pre-dose and 1 (prior to second dose), 3 (prior to fourth dose), 6 (prior to final dose), 6.17, 6.33, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 10, 12, 23, 36, 48, 72 and 96 hours post-dose |
|
|
|
| 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 plasma concentration to the elimination rate constant. | Posted | Mean | Standard Deviation | ng-hr/mL | serial pharmacokinetic blood samples collected pre-dose and 1 (prior to second dose), 3 (prior to fourth dose), 6 (prior to final dose), 6.17, 6.33, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 10, 12, 23, 36, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Electrocardiogram (ECG) Evaluation of the QTcF Interval (Colchicine) | The QT interval assesses cardiac repolarization and risk for arrhythmias. It is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. It is dependent on heart rate and is corrected (c) to aid interpretation via Fridericia's adjustment (F), and is reported as QTcF. | Posted | Mean | Standard Deviation | milliseconds | 24 hours - measured 0.5 hr prior to first dose (baseline), then 1, 3, 6, 7, 8, 10, 12, and 23 hours after first dose |
|
|
|
| Secondary | Electrocardiogram (ECG) Evaluation of the QTcF Interval (Moxifloxacin) | The QT interval assesses cardiac repolarization and risk for arrhythmias. It is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. It is dependent on heart rate and is corrected (c) to aid interpretation via Fridericia's adjustment (F), and is reported as QTcF. | Posted | Mean | Standard Deviation | milliseconds | 24 hours - measured 0.5 hr prior to dose (baseline), then 1, 3, 6, 7, 8, 10, 12, and 23 hours after dose |
|
|
|
| 0 |
| 15 |
| 15 |
| 15 |
| EG001 | Moxifloxacin | 400 mg capsule at the 6 hour point | 0 | 3 | 0 | 3 |
| flatulence | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| nausea | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| vessel puncture site pain | General disorders | MedDRA 10.1 | Systematic Assessment |
|
| dizziness | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
|
| headache | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
|
| nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| nasopharyngitis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| vomiting | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
|
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| D015363 |
| Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |