Trial Outcomes & Findings for Drug-Drug Interaction Study of Colchicine and Theophylline (NCT NCT00983905)
NCT ID: NCT00983905
Last Updated: 2010-03-02
Results Overview
The maximum or peak concentration that theophylline drug reaches in the plasma.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
serial pharmacokinetic blood samples drawn within 1 hour prior to theophylline dosing (0 hour) on Days 1 and 19, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after theophylline dose administration
Results posted on
2010-03-02
Participant Flow
Thirty (30) healthy, non-smoking, male and female volunteers, consisting of members of the community at large, were to be enrolled.
44 subjects screened, 6 were screen failures, 8 had schedule conflicts
Participant milestones
| Measure |
Theophylline Alone / With Colchicine (at Steady State)
\[All subjects received each of the study treatments.\] Each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) on Day 1 at 7:45am after an overnight fast of at least 10 hours, followed by a washout period of 4 days. On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45am and 7:45pm without regard to meals. Then, on Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)
|
|---|---|
|
Theophylline Alone
STARTED
|
30
|
|
Theophylline Alone
COMPLETED
|
29
|
|
Theophylline Alone
NOT COMPLETED
|
1
|
|
4 Day Washout Period
STARTED
|
29
|
|
4 Day Washout Period
COMPLETED
|
29
|
|
4 Day Washout Period
NOT COMPLETED
|
0
|
|
Colchicine Alone
STARTED
|
29
|
|
Colchicine Alone
COMPLETED
|
27
|
|
Colchicine Alone
NOT COMPLETED
|
2
|
|
Theophylline With Colchicine
STARTED
|
27
|
|
Theophylline With Colchicine
COMPLETED
|
27
|
|
Theophylline With Colchicine
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Theophylline Alone / With Colchicine (at Steady State)
\[All subjects received each of the study treatments.\] Each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) on Day 1 at 7:45am after an overnight fast of at least 10 hours, followed by a washout period of 4 days. On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45am and 7:45pm without regard to meals. Then, on Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)
|
|---|---|
|
Theophylline Alone
Adverse Event
|
1
|
|
Colchicine Alone
Adverse Event
|
2
|
Baseline Characteristics
Drug-Drug Interaction Study of Colchicine and Theophylline
Baseline characteristics by cohort
| Measure |
Theophylline Alone / With Colchicine (at Steady State)
n=30 Participants
\[All subjects received each of the study treatments.\] Each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) on Day 1 at 7:45am after an overnight fast of at least 10 hours, followed by a washout period of 4 days. On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45am and 7:45pm without regard to meals. Then, on Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)
|
|---|---|
|
Age, Categorical
<=18 years
|
2 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
|
25.1 years
STANDARD_DEVIATION 5.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 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
|
27 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples drawn within 1 hour prior to theophylline dosing (0 hour) on Days 1 and 19, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after theophylline dose administrationThe maximum or peak concentration that theophylline drug reaches in the plasma.
Outcome measures
| Measure |
Theophylline Alone
n=27 Participants
On Day 1, each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) at 7:45 am after an overnight fast of at least 10 hours, followed by a washout period of 4 days.
|
Theophylline With Colchicine (at Steady-state)
n=27 Participants
On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45 am and 7:45 pm without regard to meals. Then, on Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
9.76 µg/mL
Standard Deviation 2.25
|
9.79 µg/mL
Standard Deviation 1.87
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples drawn within 1 hour prior to theophylline dosing (0 hour) on Days 1 and 19, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after theophylline dose administrationThe area under the theophylline plasma concentration versus time curve, from time 0 to the time of the last measurable theophylline concentration (t), as calculated by the linear trapezoidal rule.
Outcome measures
| Measure |
Theophylline Alone
n=27 Participants
On Day 1, each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) at 7:45 am after an overnight fast of at least 10 hours, followed by a washout period of 4 days.
|
Theophylline With Colchicine (at Steady-state)
n=27 Participants
On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45 am and 7:45 pm without regard to meals. Then, on Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
|
120.80 µg-hr/mL
Standard Deviation 38.73
|
121.35 µg-hr/mL
Standard Deviation 40.06
|
PRIMARY outcome
Timeframe: serial pharmacokinetic blood samples drawn within 1 hour prior to theophylline dosing (0 hour) on Days 1 and 19, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after theophylline dose administrationThe area under the theophylline 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 theophylline plasma concentration to the elimination rate constant.
Outcome measures
| Measure |
Theophylline Alone
n=27 Participants
On Day 1, each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) at 7:45 am after an overnight fast of at least 10 hours, followed by a washout period of 4 days.
|
Theophylline With Colchicine (at Steady-state)
n=27 Participants
On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45 am and 7:45 pm without regard to meals. Then, on Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
|
127.47 µg-hr/mL
Standard Deviation 42.28
|
129.39 µg-hr/mL
Standard Deviation 44.83
|
Adverse Events
Theophylline Alone
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Colchicine Alone
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Theophylline With Steady-state Colchicine
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Theophylline Alone
n=30 participants at risk
Each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) on Day 1 at 7:45 am after an overnight fast of at least 10 hours, followed by a washout period of 4 days.
|
Colchicine Alone
n=29 participants at risk
On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45 am and 7:45 pm without regard to meals.
|
Theophylline With Steady-state Colchicine
n=27 participants at risk
On Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45 am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)
|
|---|---|---|---|
|
Ear and labyrinth disorders
ear discomfort
|
0.00%
0/30
|
3.4%
1/29 • Number of events 1
|
0.00%
0/27
|
|
Eye disorders
eye pruritus
|
3.3%
1/30 • Number of events 1
|
0.00%
0/29
|
0.00%
0/27
|
|
Gastrointestinal disorders
abdominal pain
|
3.3%
1/30 • Number of events 1
|
3.4%
1/29 • Number of events 2
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
abdominal pain upper
|
0.00%
0/30
|
10.3%
3/29 • Number of events 3
|
0.00%
0/27
|
|
Gastrointestinal disorders
diarrhoea
|
0.00%
0/30
|
27.6%
8/29 • Number of events 11
|
0.00%
0/27
|
|
Gastrointestinal disorders
dyspepsia
|
0.00%
0/30
|
3.4%
1/29 • Number of events 1
|
0.00%
0/27
|
|
Gastrointestinal disorders
nausea
|
16.7%
5/30 • Number of events 7
|
6.9%
2/29 • Number of events 3
|
0.00%
0/27
|
|
Gastrointestinal disorders
stomach discomfort
|
0.00%
0/30
|
3.4%
1/29 • Number of events 1
|
0.00%
0/27
|
|
Gastrointestinal disorders
vomiting
|
3.3%
1/30 • Number of events 1
|
10.3%
3/29 • Number of events 3
|
3.7%
1/27 • Number of events 2
|
|
General disorders
feeling hot
|
0.00%
0/30
|
3.4%
1/29 • Number of events 2
|
0.00%
0/27
|
|
Injury, poisoning and procedural complications
skin laceration
|
0.00%
0/30
|
3.4%
1/29 • Number of events 1
|
0.00%
0/27
|
|
Investigations
heart rate increased
|
0.00%
0/30
|
0.00%
0/29
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
neck pain
|
0.00%
0/30
|
0.00%
0/29
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
dizziness
|
10.0%
3/30 • Number of events 4
|
13.8%
4/29 • Number of events 5
|
7.4%
2/27 • Number of events 2
|
|
Nervous system disorders
headache
|
6.7%
2/30 • Number of events 2
|
10.3%
3/29 • Number of events 4
|
7.4%
2/27 • Number of events 2
|
|
Nervous system disorders
paraesthesia
|
0.00%
0/30
|
0.00%
0/29
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
syncope
|
0.00%
0/30
|
0.00%
0/29
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
nasal congestion
|
3.3%
1/30 • Number of events 1
|
0.00%
0/29
|
0.00%
0/27
|
|
Respiratory, thoracic and mediastinal disorders
sinus congestion
|
0.00%
0/30
|
3.4%
1/29 • Number of events 1
|
0.00%
0/27
|
|
Skin and subcutaneous tissue disorders
drug eruption
|
3.3%
1/30 • Number of events 1
|
0.00%
0/29
|
0.00%
0/27
|
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