Trial Outcomes & Findings for Drug-Drug Interaction Between Colchicine and Ritonavir (NCT NCT00983515)
NCT ID: NCT00983515
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 members from the community at large, were enrolled in the study.
48 subjects were screened, 11 were screen failures, 7 had schedule conflicts, 6 were not needed
Participant milestones
| Measure |
Colchicine Alone / With Ritonavir (at Steady-state)
\[All subjects received each of the study treatments.\] On Day 1, each subject received one colchicine 0.6 mg tablet at 7:00 a.m. after an overnight fast of at least 10 hours, followed by a washout period of 14 days. On Days 15 to 18, each subject received one 100 mg ritonavir capsule twice daily at 7:00 a.m. and 7:00 p.m. without regards to meals. Then, on Day 19, each subject received both one 0.6 mg colchicine tablet and one 100 mg ritonavir capsule at 7:00 a.m. after an overnight fast. A final dose of ritonavir was administered at 7:00 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
|
|
Ritonavir Alone
STARTED
|
24
|
|
Ritonavir Alone
COMPLETED
|
18
|
|
Ritonavir Alone
NOT COMPLETED
|
6
|
|
Colchicine With Ritonavir
STARTED
|
18
|
|
Colchicine With Ritonavir
COMPLETED
|
17
|
|
Colchicine With Ritonavir
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Colchicine Alone / With Ritonavir (at Steady-state)
\[All subjects received each of the study treatments.\] On Day 1, each subject received one colchicine 0.6 mg tablet at 7:00 a.m. after an overnight fast of at least 10 hours, followed by a washout period of 14 days. On Days 15 to 18, each subject received one 100 mg ritonavir capsule twice daily at 7:00 a.m. and 7:00 p.m. without regards to meals. Then, on Day 19, each subject received both one 0.6 mg colchicine tablet and one 100 mg ritonavir capsule at 7:00 a.m. after an overnight fast. A final dose of ritonavir was administered at 7:00 p.m. that evening.
|
|---|---|
|
Ritonavir Alone
liver panel out of range
|
6
|
|
Colchicine With Ritonavir
Lost to Follow-up
|
1
|
Baseline Characteristics
Drug-Drug Interaction Between Colchicine and Ritonavir
Baseline characteristics by cohort
| Measure |
Colchicine Alone / With Ritonavir (at Steady-state)
n=24 Participants
\[All subjects received each of the study treatments.\] On Day 1, each subject received one colchicine 0.6 mg tablet at 7:00 a.m. after an overnight fast of at least 10 hours, followed by a washout period of 14 days. On Days 15 to 18, each subject received one 100 mg ritonavir capsule twice daily at 7:00 a.m. and 7:00 p.m. without regards to meals. Then, on Day 19, each subject received both one 0.6 mg colchicine tablet and one 100 mg ritonavir capsule at 7:00 a.m. after an overnight fast. A final dose of ritonavir was administered at 7:00 p.m. that evening.
|
|---|---|
|
Age, Categorical
<=18 years
|
5 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
23.0 years
STANDARD_DEVIATION 4.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 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
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
22 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=18 Participants
On Day 1, each subject received one 0.6 mg colchicine tablet at 7:00 a.m. after an overnight fast of at least 10 hours, followed by a washout period of 14 days.
|
Colchicine With Ritonavir (at Steady-state)
n=18 Participants
On Days 15 to 18, each subject received one 100 mg ritonavir capsule twice daily at 7:00 a.m. and 7:00 p.m. without regards to meals. Then, on Day 19, each subject received both one 0.6 mg colchicine tablet and one 100 mg ritonavir capsule at 7:00 a.m. after an overnight fast. A final dose of ritonavir was administered at 7:00 p.m. that evening.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
1,869.50 pg/mL
Standard Deviation 526.94
|
4,993.06 pg/mL
Standard Deviation 1,257.07
|
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 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=18 Participants
On Day 1, each subject received one 0.6 mg colchicine tablet at 7:00 a.m. after an overnight fast of at least 10 hours, followed by a washout period of 14 days.
|
Colchicine With Ritonavir (at Steady-state)
n=18 Participants
On Days 15 to 18, each subject received one 100 mg ritonavir capsule twice daily at 7:00 a.m. and 7:00 p.m. without regards to meals. Then, on Day 19, each subject received both one 0.6 mg colchicine tablet and one 100 mg ritonavir capsule at 7:00 a.m. after an overnight fast. A final dose of ritonavir was administered at 7:00 p.m. that evening.
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
|
8,412.04 pg-hr/mL
Standard Deviation 3,992.34
|
29,048.45 pg-hr/mL
Standard Deviation 8,935.10
|
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 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=18 Participants
On Day 1, each subject received one 0.6 mg colchicine tablet at 7:00 a.m. after an overnight fast of at least 10 hours, followed by a washout period of 14 days.
|
Colchicine With Ritonavir (at Steady-state)
n=18 Participants
On Days 15 to 18, each subject received one 100 mg ritonavir capsule twice daily at 7:00 a.m. and 7:00 p.m. without regards to meals. Then, on Day 19, each subject received both one 0.6 mg colchicine tablet and one 100 mg ritonavir capsule at 7:00 a.m. after an overnight fast. A final dose of ritonavir was administered at 7:00 p.m. that evening.
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
|
10,410.73 pg-hr/mL
Standard Deviation 4,734.38
|
35,276.22 pg-hr/mL
Standard Deviation 10,508.55
|
Adverse Events
Colchicine Alone
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Ritonavir Alone
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Colchicine With Steady-state Ritonavir
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 Day 1, each subject received one 0.6 mg colchicine tablet at 7:00 a.m. after an overnight fast of at least 10 hours, followed by a washout period of 14 days.
|
Ritonavir Alone
n=18 participants at risk
On Days 15 to 18, each subject received one 100 mg ritonavir capsule twice daily at 7:00 a.m. and 7:00 p.m. without regards to meals.
|
Colchicine With Steady-state Ritonavir
n=18 participants at risk
On Day 19, each subject received both one 0.6 mg colchicine tablet and one 100 mg ritonavir capsule at 7:00 a.m. after an overnight fast. A final dose of ritonavir was administered at 7:00 p.m. that evening.
|
|---|---|---|---|
|
Gastrointestinal disorders
upper abdominal pain
|
4.2%
1/24 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
nausea
|
4.2%
1/24 • Number of events 1
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Gastrointestinal disorders
vomiting
|
4.2%
1/24 • Number of events 2
|
0.00%
0/18
|
0.00%
0/18
|
|
Infections and infestations
gastroenteritis viral
|
4.2%
1/24 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Nervous system disorders
dysgeusia
|
4.2%
1/24 • Number of events 1
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Nervous system disorders
headache
|
4.2%
1/24 • Number of events 1
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Reproductive system and breast disorders
dysmenorrhoea
|
0.00%
0/24
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
0.00%
0/24
|
5.6%
1/18 • Number of events 1
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
pharyngolaryngeal pain
|
0.00%
0/24
|
5.6%
1/18 • Number of events 1
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
rhinorrhoea
|
8.3%
2/24 • Number of events 2
|
0.00%
0/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
sinus congestion
|
0.00%
0/24
|
11.1%
2/18 • Number of events 2
|
0.00%
0/18
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60