Trial Outcomes & Findings for Drug-Drug Interaction Study of Colchicine and Clarithromycin (NCT NCT00984061)
NCT ID: NCT00984061
Last Updated: 2009-10-15
Results Overview
The maximum or peak concentration that colchicine reaches in the plasma.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
serial pharmacokinetic blood samples collected immediately prior to dosing on Days 1 and 29, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours after dose administration
Results posted on
2009-10-15
Participant Flow
Twenty-four (24) healthy, non-smoking, adult male and female volunteers, consisting of members of the community at large, were enrolled.
56 subjects screened, 32 were screen failures
Participant milestones
| Measure |
Colchicine Alone / With Clarithromycin
\[All subjects received each of the study treatments.\] Each subject received one colchicine 0.6 mg tablet on Day 1 at 9:00 a.m. after an overnight fast of at least 10 hours, followed by a 21 day washout period. On Day 22, subjects began taking one 250 mg clarithromycin tablet every 12 hours at 8:00 a.m. and 8:00 p.m. for 7 days without regard to meals. Then, on Day 29, each subject received one colchicine 0.6 mg tablet along with final dose of 250 mg clarithromycin at 9:00 a.m. after an overnight fast of at least 10 hours.
|
|---|---|
|
Colchicine Alone
STARTED
|
24
|
|
Colchicine Alone
COMPLETED
|
24
|
|
Colchicine Alone
NOT COMPLETED
|
0
|
|
21 Day Washout Period
STARTED
|
24
|
|
21 Day Washout Period
COMPLETED
|
24
|
|
21 Day Washout Period
NOT COMPLETED
|
0
|
|
Clarithromycin Alone
STARTED
|
24
|
|
Clarithromycin Alone
COMPLETED
|
23
|
|
Clarithromycin Alone
NOT COMPLETED
|
1
|
|
Colchicine With Clarithromycin
STARTED
|
23
|
|
Colchicine With Clarithromycin
COMPLETED
|
23
|
|
Colchicine With Clarithromycin
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Colchicine Alone / With Clarithromycin
\[All subjects received each of the study treatments.\] Each subject received one colchicine 0.6 mg tablet on Day 1 at 9:00 a.m. after an overnight fast of at least 10 hours, followed by a 21 day washout period. On Day 22, subjects began taking one 250 mg clarithromycin tablet every 12 hours at 8:00 a.m. and 8:00 p.m. for 7 days without regard to meals. Then, on Day 29, each subject received one colchicine 0.6 mg tablet along with final dose of 250 mg clarithromycin at 9:00 a.m. after an overnight fast of at least 10 hours.
|
|---|---|
|
Clarithromycin Alone
Protocol Violation
|
1
|
Baseline Characteristics
Drug-Drug Interaction Study of Colchicine and Clarithromycin
Baseline characteristics by cohort
| Measure |
Colchicine Alone / With Clarithromycin
n=24 Participants
\[All subjects received each of the study treatments.\] Each subject received one colchicine 0.6 mg tablet on Day 1 at 9:00 a.m. after an overnight fast of at least 10 hours, followed by a 21 day washout period. On Day 22, subjects began taking one 250 mg clarithromycin tablet every 12 hours at 8:00 a.m. and 8:00 p.m. for 7 days without regard to meals. Then, on Day 29, each subject received one colchicine 0.6 mg tablet along with final dose of 250 mg clarithromycin at 9:00 a.m. after an overnight fast of at least 10 hours.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
22.3 years
STANDARD_DEVIATION 4.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
24 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples collected immediately prior to dosing on Days 1 and 29, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours after dose administrationThe maximum or peak concentration that colchicine reaches in the plasma.
Outcome measures
| Measure |
Colchicine Alone
n=23 Participants
Each subject received one colchicine 0.6 mg tablet on Day 1 at 9:00 a.m. after an overnight fast of at least 10 hours, followed by a 21 day washout period.
|
Colchicine With Clarithromycin
n=23 Participants
On Day 22, subjects began taking one 250 mg clarithromycin tablet every 12 hours at 8:00 a.m. and 8:00 p.m. for 7 days without regard to meals. Then, on Day 29, each subject received one colchicine 0.6 mg tablet along with final dose of 250 mg clarithromycin at 9:00 a.m. after an overnight fast of at least 10 hours.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
2.84 ng/mL
Standard Deviation 0.88
|
8.44 ng/mL
Standard Deviation 1.49
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples collected immediately prior to dosing on Days 1 and 29, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours after dose administrationThe area under the colchicine plasma concentration versus time curve beginning from the first dose (time 0) to the last measurable colchicine concentration (time t), as calculated by the linear trapezoidal method.
Outcome measures
| Measure |
Colchicine Alone
n=23 Participants
Each subject received one colchicine 0.6 mg tablet on Day 1 at 9:00 a.m. after an overnight fast of at least 10 hours, followed by a 21 day washout period.
|
Colchicine With Clarithromycin
n=23 Participants
On Day 22, subjects began taking one 250 mg clarithromycin tablet every 12 hours at 8:00 a.m. and 8:00 p.m. for 7 days without regard to meals. Then, on Day 29, each subject received one colchicine 0.6 mg tablet along with final dose of 250 mg clarithromycin at 9:00 a.m. after an overnight fast of at least 10 hours.
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
|
12.37 ng-hr/mL
Standard Deviation 4.66
|
41.95 ng-hr/mL
Standard Deviation 9.78
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples collected immediately prior to dosing on Days 1 and 29, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours after dose administrationThe area under the colchicine 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 Alone
n=23 Participants
Each subject received one colchicine 0.6 mg tablet on Day 1 at 9:00 a.m. after an overnight fast of at least 10 hours, followed by a 21 day washout period.
|
Colchicine With Clarithromycin
n=23 Participants
On Day 22, subjects began taking one 250 mg clarithromycin tablet every 12 hours at 8:00 a.m. and 8:00 p.m. for 7 days without regard to meals. Then, on Day 29, each subject received one colchicine 0.6 mg tablet along with final dose of 250 mg clarithromycin at 9:00 a.m. after an overnight fast of at least 10 hours.
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
|
15.53 ng-hr/mL
Standard Deviation 7.70
|
52.62 ng-hr/mL
Standard Deviation 12.02
|
Adverse Events
Colchicine Alone
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Clarithromycin Alone
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Colchicine With Clarithromycin
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 Alone
n=24 participants at risk
On the morning of Day 1 after a fast of at least 10 hours, all subjects received a single dose of colchicine 0.6 mg.
|
Clarithromycin Alone
n=23 participants at risk
On the evening of Day 22, subjects began taking (on an outpatient basis) one tablet of clarithromycin 250 mg every 12 hours for 7 days without regard to meals.
|
Colchicine With Clarithromycin
n=23 participants at risk
On the morning of Day 29 after an overnight fast of at least 10 hours, all subjects received a single dose of colchicine 0.6 mg along with the last dose of clarithromycin.
|
|---|---|---|---|
|
Ear and labyrinth disorders
hypoacusis
|
4.2%
1/24 • Number of events 1
|
0.00%
0/23
|
0.00%
0/23
|
|
Gastrointestinal disorders
abdominal pain upper
|
0.00%
0/24
|
4.3%
1/23 • Number of events 1
|
0.00%
0/23
|
|
Gastrointestinal disorders
diarrhea
|
0.00%
0/24
|
0.00%
0/23
|
8.7%
2/23 • Number of events 2
|
|
Gastrointestinal disorders
nausea
|
8.3%
2/24 • Number of events 2
|
0.00%
0/23
|
8.7%
2/23 • Number of events 2
|
|
Gastrointestinal disorders
stomach discomfort
|
0.00%
0/24
|
4.3%
1/23 • Number of events 1
|
0.00%
0/23
|
|
General disorders
chest pain
|
0.00%
0/24
|
0.00%
0/23
|
4.3%
1/23 • Number of events 1
|
|
General disorders
vessel puncture site hematoma
|
4.2%
1/24 • Number of events 1
|
0.00%
0/23
|
0.00%
0/23
|
|
Injury, poisoning and procedural complications
skin laceration
|
4.2%
1/24 • Number of events 1
|
0.00%
0/23
|
0.00%
0/23
|
|
Musculoskeletal and connective tissue disorders
pain in extremity
|
8.3%
2/24 • Number of events 2
|
4.3%
1/23 • Number of events 2
|
0.00%
0/23
|
|
Nervous system disorders
dizziness
|
4.2%
1/24 • Number of events 1
|
0.00%
0/23
|
0.00%
0/23
|
|
Nervous system disorders
headache
|
12.5%
3/24 • Number of events 4
|
8.7%
2/23 • Number of events 2
|
8.7%
2/23 • Number of events 2
|
|
Nervous system disorders
syncope
|
8.3%
2/24 • Number of events 2
|
0.00%
0/23
|
0.00%
0/23
|
|
Nervous system disorders
vision blurred
|
4.2%
1/24 • Number of events 2
|
0.00%
0/23
|
4.3%
1/23 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
0.00%
0/24
|
4.3%
1/23 • Number of events 1
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
4.2%
1/24 • Number of events 1
|
0.00%
0/23
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
pharyngolaryngeal pain
|
0.00%
0/24
|
4.3%
1/23 • Number of events 1
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
sinus congestion
|
4.2%
1/24 • Number of events 1
|
0.00%
0/23
|
0.00%
0/23
|
|
Vascular disorders
pallor
|
8.3%
2/24 • Number of events 2
|
0.00%
0/23
|
0.00%
0/23
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60