Trial Outcomes & Findings for Drug-Drug Interaction Study Between Colchicine and Diltiazem ER (NCT NCT00983372)
NCT ID: NCT00983372
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 immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after dose administration
Results posted on
2009-10-15
Participant Flow
Twenty-four (24) healthy, non-smoking , male and female volunteers, consisting of members of the community at large, were enrolled in the study.
53 subjects were screened, 13 were screen failures, 14 had schedule conflicts, 1 transferred to a different study, and 1 was not needed
Participant milestones
| Measure |
Colchicine Alone / With Diltiazem (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 of at least 10 hours, followed by a washout period of 14 days. On Days 15 to 20, each subject received one 240 mg diltiazem ER capsule at 7:15 a.m. Then, on Day 21, each subject received both one 0.6 mg colchicine tablet and one 240 mg diltiazem ER capsule at 7:15 a.m. after an overnight fast of at least 10 hours.
|
|---|---|
|
Colchicine Alone
STARTED
|
24
|
|
Colchicine Alone
COMPLETED
|
24
|
|
Colchicine Alone
NOT COMPLETED
|
0
|
|
14 Day Washout Period
STARTED
|
24
|
|
14 Day Washout Period
COMPLETED
|
23
|
|
14 Day Washout Period
NOT COMPLETED
|
1
|
|
Diltiazem ER Alone
STARTED
|
23
|
|
Diltiazem ER Alone
COMPLETED
|
20
|
|
Diltiazem ER Alone
NOT COMPLETED
|
3
|
|
Colchicine With Diltiazem ER
STARTED
|
20
|
|
Colchicine With Diltiazem ER
COMPLETED
|
20
|
|
Colchicine With Diltiazem ER
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Colchicine Alone / With Diltiazem (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 of at least 10 hours, followed by a washout period of 14 days. On Days 15 to 20, each subject received one 240 mg diltiazem ER capsule at 7:15 a.m. Then, on Day 21, each subject received both one 0.6 mg colchicine tablet and one 240 mg diltiazem ER capsule at 7:15 a.m. after an overnight fast of at least 10 hours.
|
|---|---|
|
14 Day Washout Period
Withdrawal by Subject
|
1
|
|
Diltiazem ER Alone
missed diltiazem dose
|
2
|
|
Diltiazem ER Alone
Adverse Event
|
1
|
Baseline Characteristics
Drug-Drug Interaction Study Between Colchicine and Diltiazem ER
Baseline characteristics by cohort
| Measure |
Colchicine Alone / With Diltiazem (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 of at least 10 hours, followed by a washout period of 14 days. On Days 15 to 20, each subject received one 240 mg diltiazem ER capsule at 7:15 a.m. Then, on Day 21, each subject received both one 0.6 mg colchicine tablet and one 240 mg diltiazem ER capsule at 7:15 a.m. after an overnight fast of at least 10 hours.
|
|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
23 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
28.0 years
STANDARD_DEVIATION 8.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
18 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
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 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 immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 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=20 Participants
Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast of at least 10 hours, followed by a washout period of 14 days.
|
Colchicine With Diltiazem (at Steady-state)
n=20 Participants
On Days 15 to 20, each subject received one 240 mg diltiazem ER capsule at 7:15 a.m. Then, on Day 21, each subject received both one 0.6 mg colchicine tablet and one 240 mg diltiazem ER capsule at 7:15 a.m. after an overnight fast of at least 10 hours.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
2,172.32 pg/mL
Standard Deviation 868.72
|
2,802.90 pg/mL
Standard Deviation 1,245.01
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after dose administrationThe 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 Alone
n=20 Participants
Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast of at least 10 hours, followed by a washout period of 14 days.
|
Colchicine With Diltiazem (at Steady-state)
n=20 Participants
On Days 15 to 20, each subject received one 240 mg diltiazem ER capsule at 7:15 a.m. Then, on Day 21, each subject received both one 0.6 mg colchicine tablet and one 240 mg diltiazem ER capsule at 7:15 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)]
|
10,035.57 pg-hr/mL
Standard Deviation 4,562.57
|
17,729.64 pg-hr/mL
Standard Deviation 8,642.59
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 21, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after dose administrationThe 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 Alone
n=20 Participants
Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast of at least 10 hours, followed by a washout period of 14 days.
|
Colchicine With Diltiazem (at Steady-state)
n=20 Participants
On Days 15 to 20, each subject received one 240 mg diltiazem ER capsule at 7:15 a.m. Then, on Day 21, each subject received both one 0.6 mg colchicine tablet and one 240 mg diltiazem ER capsule at 7:15 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-∞)]
|
12,025.69 pg-hr/mL
Standard Deviation 5,418.95
|
22,485.97 pg-hr/mL
Standard Deviation 10,994.16
|
Adverse Events
Colchicine Alone
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Diltiazem Alone
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Colchicine With Steady-state Diltiazem
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
Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast of at least 10 hours, followed by a washout period of 14 days.
|
Diltiazem Alone
n=21 participants at risk
On Days 15 to 20, each subject received one 240 mg diltiazem ER capsule at 7:15 a.m.
|
Colchicine With Steady-state Diltiazem
n=20 participants at risk
On Day 21, each subject received both one 0.6 mg colchicine tablet and one 240 mg diltiazem ER capsule at 7:15 a.m. after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Eye disorders
dry eye
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
|
Eye disorders
eye irritation
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
|
Gastrointestinal disorders
dyspepsia
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
|
Gastrointestinal disorders
nausea
|
4.2%
1/24 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
vomiting
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
|
General disorders
chest pain
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
musculoskeletal pain
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
|
Nervous system disorders
dizziness
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
|
Nervous system disorders
headache
|
8.3%
2/24 • Number of events 2
|
38.1%
8/21 • Number of events 11
|
15.0%
3/20 • Number of events 3
|
|
Nervous system disorders
lethargy
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
pharyngolaryngeal pain
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
rhinorrhea
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
contact dermatitis
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60