Trial Outcomes & Findings for Bioequivalence Study of Colchicine Tablets (NCT NCT01021020)
NCT ID: NCT01021020
Last Updated: 2009-12-09
Results Overview
The maximum or peak concentration that colchicine reaches in the plasma.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
28 participants
Primary outcome timeframe
serial pharmacokinetic blood samples collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Results posted on
2009-12-09
Participant Flow
Twenty-eight (28) healthy, non-smoking, adult male and female volunteers, consisting of university students and members of the community at large, were to be enrolled.
75 subjects screened, 47 were screen failures
Participant milestones
| Measure |
Colchicine (Fasted),Colchicine (Fed),Colchicine/Probenecid
All subjects received each of the three study treatments in a randomly assigned sequence of dosing periods. On the morning of Days 1, 15, and 29, each subject received one of the following three treatments: 1) one tablet of colchicine 0.6 mg after an overnight fast of at least 13.5 hours, 2) one tablet of colchicine 0.6 mg after a high-fat breakfast, or 3) one tablet of colchicine 0.5 mg/ probenecid 500 mg following an overnight fast of at least 13.5 hours.
|
|---|---|
|
Period I
STARTED
|
28
|
|
Period I
COMPLETED
|
26
|
|
Period I
NOT COMPLETED
|
2
|
|
14 Day Washout Period A
STARTED
|
26
|
|
14 Day Washout Period A
COMPLETED
|
25
|
|
14 Day Washout Period A
NOT COMPLETED
|
1
|
|
Period II
STARTED
|
25
|
|
Period II
COMPLETED
|
25
|
|
Period II
NOT COMPLETED
|
0
|
|
14 Day Washout Period B
STARTED
|
25
|
|
14 Day Washout Period B
COMPLETED
|
25
|
|
14 Day Washout Period B
NOT COMPLETED
|
0
|
|
Period III
STARTED
|
25
|
|
Period III
COMPLETED
|
25
|
|
Period III
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Colchicine (Fasted),Colchicine (Fed),Colchicine/Probenecid
All subjects received each of the three study treatments in a randomly assigned sequence of dosing periods. On the morning of Days 1, 15, and 29, each subject received one of the following three treatments: 1) one tablet of colchicine 0.6 mg after an overnight fast of at least 13.5 hours, 2) one tablet of colchicine 0.6 mg after a high-fat breakfast, or 3) one tablet of colchicine 0.5 mg/ probenecid 500 mg following an overnight fast of at least 13.5 hours.
|
|---|---|
|
Period I
Protocol Violation
|
1
|
|
Period I
Withdrawal by Subject
|
1
|
|
14 Day Washout Period A
Physician Decision
|
1
|
Baseline Characteristics
Bioequivalence Study of Colchicine Tablets
Baseline characteristics by cohort
| Measure |
Colchicine(Fasted),Colchicine(Fed),Colchicine/Probenecid
n=28 Participants
All subjects received all study treatments in a randomly assigned sequence of dosing periods. On the morning of Days 1, 15, and 29, each subject received one of the following three treatments: 1) one tablet of colchicine 0.6 mg after an overnight fast of at least 13.5 hours, 2) one tablet of colchicine 0.6 mg after a high-fat breakfast, or 3) one tablet of colchicine 0.5 mg/ probenecid 500 mg following an overnight fast of at least 13.5 hours.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
28 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
23.7 years
STANDARD_DEVIATION 5.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
28 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-doseThe maximum or peak concentration that colchicine reaches in the plasma.
Outcome measures
| Measure |
Colchicine 0.6 mg (Fasted)
n=25 Participants
Subjects received one tablet of colchicine 0.6 mg after an overnight fast.
|
Colchicine (High-fat Meal)
n=25 Participants
Subjects received one tablet of colchicine 0.6 mg after a high-fat breakfast.
|
Colchicine 0.5 mg/ Probenecid 500 mg (Fasted)
n=25 Participants
Subjects received one tablet of colchicine 0.5 mg/ probenecid 500 mg following an overnight fast.
|
|---|---|---|---|
|
Maximal Plasma Concentration (Cmax)
|
2,503.04 pg/mL
Standard Deviation 722.05
|
2,496.88 pg/mL
Standard Deviation 695.09
|
1,706.03 pg/mL
Standard Deviation 560.73
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-doseThe 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.
Outcome measures
| Measure |
Colchicine 0.6 mg (Fasted)
n=25 Participants
Subjects received one tablet of colchicine 0.6 mg after an overnight fast.
|
Colchicine (High-fat Meal)
n=25 Participants
Subjects received one tablet of colchicine 0.6 mg after a high-fat breakfast.
|
Colchicine 0.5 mg/ Probenecid 500 mg (Fasted)
n=25 Participants
Subjects received one tablet of colchicine 0.5 mg/ probenecid 500 mg following an overnight fast.
|
|---|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
|
12,588.61 pg-hr/mL
Standard Deviation 6,120.73
|
10,490.95 pg-hr/mL
Standard Deviation 4,025.80
|
8,090.05 pg-hr/mL
Standard Deviation 6,111.99
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dosePopulation: Colchicine(fasted)-could not be determined for Subject 25. Colchicine(high-fat meal)-could not be determined for Subjects 22,25, and 28. Colchicine/Probenecid(fasted)-could not be determined for Subject 25.
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.
Outcome measures
| Measure |
Colchicine 0.6 mg (Fasted)
n=24 Participants
Subjects received one tablet of colchicine 0.6 mg after an overnight fast.
|
Colchicine (High-fat Meal)
n=22 Participants
Subjects received one tablet of colchicine 0.6 mg after a high-fat breakfast.
|
Colchicine 0.5 mg/ Probenecid 500 mg (Fasted)
n=24 Participants
Subjects received one tablet of colchicine 0.5 mg/ probenecid 500 mg following an overnight fast.
|
|---|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
|
14,112.52 pg-hr/mL
Standard Deviation 5,595.40
|
11,404.09 pg-hr/mL
Standard Deviation 2,895.68
|
8,481.41 pg-hr/mL
Standard Deviation 2,829.75
|
Adverse Events
Colchicine 0.6 mg (Fasted)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Colchicine 0.6 mg (Fed)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Colchicine 0.5 mg/Probenecid 500 mg (Fasted)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Colchicine 0.6 mg (Fasted)
n=26 participants at risk
Subjects received one tablet of colchicine 0.6mg after an overnight fast of at least 13.5 hours.
|
Colchicine 0.6 mg (Fed)
n=27 participants at risk
Subjects received one tablet of colchicine 0.6 mg after a high-fat meal.
|
Colchicine 0.5 mg/Probenecid 500 mg (Fasted)
n=27 participants at risk
Subjects received one tablet of colchicine 0.5 mg/ probenecid 500 mg after an overnight fast of at least 13.5 hours.
|
|---|---|---|---|
|
Gastrointestinal disorders
nausea
|
0.00%
0/26
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
7.4%
2/27 • Number of events 2
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
|
Gastrointestinal disorders
stomach discomfort
|
0.00%
0/26
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
3.7%
1/27 • Number of events 1
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
|
Gastrointestinal disorders
vomiting
|
0.00%
0/26
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
3.7%
1/27 • Number of events 1
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
|
Musculoskeletal and connective tissue disorders
paresthesia
|
3.8%
1/26 • Number of events 1
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
|
Nervous system disorders
dizziness
|
7.7%
2/26 • Number of events 2
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
3.7%
1/27 • Number of events 1
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
7.4%
2/27 • Number of events 2
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
|
Nervous system disorders
headache
|
3.8%
1/26 • Number of events 1
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
3.7%
1/27 • Number of events 1
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
3.7%
1/27 • Number of events 1
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
|
Respiratory, thoracic and mediastinal disorders
nasopharyngitis
|
3.8%
1/26 • Number of events 1
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
|
Respiratory, thoracic and mediastinal disorders
pharyngolaryngeal pain
|
0.00%
0/26
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
3.7%
1/27 • Number of events 1
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
|
Respiratory, thoracic and mediastinal disorders
rhinorrhoea
|
3.8%
1/26 • Number of events 1
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
|
Respiratory, thoracic and mediastinal disorders
sinus headache
|
3.8%
1/26 • Number of events 1
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
|
Skin and subcutaneous tissue disorders
cold sweat
|
0.00%
0/26
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
3.7%
1/27 • Number of events 1
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
0.00%
0/27
28 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving all interventions. 26 subjects were administered colchicine 0.6 mg tablets (fasted). 27 subjects were administered colchicine 0.6 mg tablets(fed). 27 subjects were co-administered colchicine 0.5 mg/probenecid 500 mg tabs (fasted).
|
Additional Information
Medical Affairs Director
Mutual Pharmaceutical Company, Inc.
Phone: 215-697-1743
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60