Trial Outcomes & Findings for Drug-Drug Interaction Study Between Colchicine and Ketoconazole (NCT NCT00983216)
NCT ID: NCT00983216
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 drawn within 1 hour prior to colchicine dosing (0 hour) on Days 1 and 19, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours after colchicine dose administration
Results posted on
2009-10-15
Participant Flow
Twenty-four (24) healthy, non-smoking, male and female volunteers, consisting of volunteers from the community at large, were enrolled in the study.
55 subjects were screened, 12 were screen failures, 7 had schedule conflicts, 1 was not used due to history of non-compliance, and 12 were not needed
Participant milestones
| Measure |
Colchicine Alone / With Ketoconazole (at Steady-state)
\[All subjects received each of the study treatments.\] Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast, followed by a washout period of 14 days. On Day 15, subjects began taking one 200 mg ketoconazole tablet twice daily at 7:15 a.m. and at 7:15 p.m. without regard to meals. Then, on Day 19, each subject received both one 0.6 mg colchicine tablet and one ketoconazole 200 mg tablet at 7:15 a.m. after an overnight fast. A final dose of ketoconazole was administered at 7:15 p.m. that evening.
|
|---|---|
|
Colchicine Alone
STARTED
|
24
|
|
Colchicine Alone
COMPLETED
|
24
|
|
Colchicine Alone
NOT COMPLETED
|
0
|
|
14 Day Washout Period
STARTED
|
24
|
|
14 Day Washout Period
COMPLETED
|
24
|
|
14 Day Washout Period
NOT COMPLETED
|
0
|
|
Ketoconazole Alone
STARTED
|
24
|
|
Ketoconazole Alone
COMPLETED
|
24
|
|
Ketoconazole Alone
NOT COMPLETED
|
0
|
|
Colchicine With Ketoconazole
STARTED
|
24
|
|
Colchicine With Ketoconazole
COMPLETED
|
24
|
|
Colchicine With Ketoconazole
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Drug-Drug Interaction Study Between Colchicine and Ketoconazole
Baseline characteristics by cohort
| Measure |
Colchicine Alone / With Ketoconazole (at Steady-state)
n=24 Participants
\[All subjects received each of the study treatments.\] Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast, followed by a washout period of 14 days. On Day 15, subjects began taking one 200 mg ketoconazole tablet twice daily at 7:15 a.m. and at 7:15 p.m. without regard to meals. Then, on Day 19, each subject received both one 0.6 mg colchicine tablet and one ketoconazole 200 mg tablet at 7:15 a.m. after an overnight fast. A final dose of ketoconazole was administered at 7:15 p.m. that evening.
|
|---|---|
|
Age, Categorical
<=18 years
|
2 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
22 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
24.4 years
STANDARD_DEVIATION 5.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 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
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples drawn within 1 hour prior to colchicine dosing (0 hour) on Days 1 and 19, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours after colchicine dose administrationThe maximum or peak concentration that colchicine reaches in the plasma.
Outcome measures
| Measure |
Colchicine Alone
n=24 Participants
Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast, followed by a washout period of 14 days.
|
Colchicine With Ketoconazole (at Steady-state)
n=24 Participants
On Day 15, subjects began taking ketoconazole 200 mg twice daily at 7:15 a.m. and at 7:15 p.m. without regard to meals. Then, on the morning of Day 19 after an overnight fast of at least 10 hours, all subjects received a single dose of colchicine 0.6 mg along with ketoconazole 200 mg. A final dose of ketoconazole was administered at 7:15 p.m. that evening.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
2,779.08 pg/mL
Standard Deviation 1,036.89
|
5,266.92 pg/mL
Standard Deviation 1,461.66
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples drawn within 1 hour prior to colchicine dosing (0 hour) on Days 1 and 19, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours after colchicine dose administrationThe area under the colchicine 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 Alone
n=24 Participants
Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast, followed by a washout period of 14 days.
|
Colchicine With Ketoconazole (at Steady-state)
n=24 Participants
On Day 15, subjects began taking ketoconazole 200 mg twice daily at 7:15 a.m. and at 7:15 p.m. without regard to meals. Then, on the morning of Day 19 after an overnight fast of at least 10 hours, all subjects received a single dose of colchicine 0.6 mg along with ketoconazole 200 mg. A final dose of ketoconazole was administered at 7:15 p.m. that evening.
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
|
11,988.61 pg-hr/mL
Standard Deviation 4,836.01
|
34,382.82 pg-hr/mL
Standard Deviation 9,445.74
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples drawn within 1 hour prior to colchicine dosing (0 hour) on Days 1 and 19, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours after colchicine 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=24 Participants
Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast, followed by a washout period of 14 days.
|
Colchicine With Ketoconazole (at Steady-state)
n=24 Participants
On Day 15, subjects began taking ketoconazole 200 mg twice daily at 7:15 a.m. and at 7:15 p.m. without regard to meals. Then, on the morning of Day 19 after an overnight fast of at least 10 hours, all subjects received a single dose of colchicine 0.6 mg along with ketoconazole 200 mg. A final dose of ketoconazole was administered at 7:15 p.m. that evening.
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
|
14,314.09 pg-hr/mL
Standard Deviation 5,991.79
|
43,680.90 pg-hr/mL
Standard Deviation 11,673.08
|
Adverse Events
Colchicine Alone
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Ketoconazole Alone
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Colchicine With Ketoconazole (at Steady-state)
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Colchicine Alone
n=24 participants at risk
Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast, followed by a washout period of 14 days.
|
Ketoconazole Alone
n=24 participants at risk
On Day 15 to 18, subjects took ketoconazole 200 mg twice daily at 7:15 a.m. and at 7:15 p.m. without regard to meals.
|
Colchicine With Ketoconazole (at Steady-state)
n=24 participants at risk
On the morning of Day 19 after an overnight fast of at least 10 hours, all subjects received a single dose of colchicine 0.6 mg along with ketoconazole 200 mg. A final dose of ketoconazole was administered at 7:15 p.m. that evening.
|
|---|---|---|---|
|
Gastrointestinal disorders
nausea
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
Nervous system disorders
dizziness
|
0.00%
0/24
|
0.00%
0/24
|
8.3%
2/24 • Number of events 2
|
|
Nervous system disorders
headache
|
12.5%
3/24 • Number of events 3
|
12.5%
3/24 • Number of events 4
|
20.8%
5/24 • Number of events 6
|
|
Reproductive system and breast disorders
polymenorrhoea
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60