Trial Outcomes & Findings for Drug - Drug Interaction Study Between Quinine Sulfate and Theophylline (NCT NCT00779259)
NCT ID: NCT00779259
Last Updated: 2009-10-28
Results Overview
The maximum or peak concentration that the drug reaches in the plasma.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Serial pharmacokinetic blood samples for theophylline collected on Days 1 and 12 before dosing and for 48 hours post-dose. Serial pharmacokinetic blood samples for quinine collected on Days 11 and 12 before dosing and for 8 hours after the morning dose.
Results posted on
2009-10-28
Participant Flow
Twenty-four (24) healthy, non-smoking, adult male volunteers from the community at large were enrolled.
Fifty-two (52) subjects were screened. Ten (10) were screen failures, eight (8) did not return and ten (10) were discharged.
Participant milestones
| Measure |
Theophylline Alone, Quinine Alone, Theophylline With Quinine
This study was done in two cohorts, each receiving the same dosing regimen. For each cohort, all subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80 mg/15 ml concentration) at 7:00am on Day 1 following an overnight fast of at least 10 hours. After a 4-day washout period, subjects received 648 mg of quinine sulfate (2 x 324 mg capsules) every 8 hours (dosing occurred at 7am, 3pm and 11pm daily) starting with the 3pm dose on Day 5 and continuing through the morning dose on Day 12. Subjects also received a single 300 mg dose of theophylline along with their 648 mg quinine sulfate dose on the morning of Day 12.
|
|---|---|
|
Theophylline Alone
STARTED
|
24
|
|
Theophylline Alone
COMPLETED
|
24
|
|
Theophylline Alone
NOT COMPLETED
|
0
|
|
4 Day Washout Period
STARTED
|
24
|
|
4 Day Washout Period
COMPLETED
|
24
|
|
4 Day Washout Period
NOT COMPLETED
|
0
|
|
Quinine Alone
STARTED
|
24
|
|
Quinine Alone
COMPLETED
|
22
|
|
Quinine Alone
NOT COMPLETED
|
2
|
|
Theophylline With Quinine
STARTED
|
22
|
|
Theophylline With Quinine
COMPLETED
|
22
|
|
Theophylline With Quinine
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Theophylline Alone, Quinine Alone, Theophylline With Quinine
This study was done in two cohorts, each receiving the same dosing regimen. For each cohort, all subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80 mg/15 ml concentration) at 7:00am on Day 1 following an overnight fast of at least 10 hours. After a 4-day washout period, subjects received 648 mg of quinine sulfate (2 x 324 mg capsules) every 8 hours (dosing occurred at 7am, 3pm and 11pm daily) starting with the 3pm dose on Day 5 and continuing through the morning dose on Day 12. Subjects also received a single 300 mg dose of theophylline along with their 648 mg quinine sulfate dose on the morning of Day 12.
|
|---|---|
|
Quinine Alone
Adverse Event
|
2
|
Baseline Characteristics
Drug - Drug Interaction Study Between Quinine Sulfate and Theophylline
Baseline characteristics by cohort
| Measure |
Theophylline Alone, Quinine Alone, Theophylline With Quinine
n=24 Participants
This study was done in two cohorts, each receiving the same dosing regimen. For each cohort, all subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80 mg/15 ml concentration) at 7:00am on Day 1 following an overnight fast of at least 10 hours. After a 4-day washout period, subjects received 648 mg of quinine sulfate (2 x 324 mg capsules) every 8 hours (dosing occurred at 7am, 3pm and 11pm daily) starting with the 3pm dose on Day 5 and continuing through the morning dose on Day 12. Subjects also received a single 300 mg dose of theophylline along with their 648 mg quinine sulfate dose on the morning of Day 12.
|
|---|---|
|
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
|
27.25 years
STANDARD_DEVIATION 6.038 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 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 for theophylline collected on Days 1 and 12 before dosing and for 48 hours post-dose. Serial pharmacokinetic blood samples for quinine collected on Days 11 and 12 before dosing and for 8 hours after the morning dose.Population: A total of 24 healthy adult male subjects participated in this study, 22 of whom completed. Pharmacokinetic analyses of theophylline are based on 19 subjects (data for 2 subjects excluded due to vomiting post-dose and for 1 subject as an outlier. Pharmacokinetic analyses of quinine are based on 20 subjects (excluding the two who vomited).
The maximum or peak concentration that the drug reaches in the plasma.
Outcome measures
| Measure |
Theophylline Alone
n=19 Participants
At 7am on Day 1 after a fast of at least 10 hours, all subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration)followed by a 4-day washout period.
|
Quinine Alone
n=20 Participants
On Day 5 in the afternoon, dosing of quinine sulfate (2 x 324 mg capsules) was initiated and continued every 8 hours without regard to meals through Day 11.
|
Theophylline in the Presence of Quinine
n=19 Participants
At 7am on Day 12 after a fast of at least 10 hours, subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration) and quinine sulfate (2 x 324 mg capsules).
|
Quinine in the Presence of Theophylline
n=20 Participants
At 7am on Day 12 after a fast of at least 10 hours, subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration) and quinine sulfate (2 x 324 mg capsules).
|
|---|---|---|---|---|
|
Maximum Plasma Concentration(Cmax)
|
9.58 ug/mL
Standard Deviation 1.66
|
6.63 ug/mL
Standard Deviation 1.63
|
9.81 ug/mL
Standard Deviation 1.35
|
7.47 ug/mL
Standard Deviation 1.77
|
PRIMARY outcome
Timeframe: Serial pharmacokinetic blood samples for theophylline collected on Days 1 and 12 before dosing and for 48 hours post-dose. Serial pharmacokinetic blood samples for quinine collected on Days 11 and 12 before dosing and for 8 hours after the morning dose.Population: A total of 24 healthy adult male subjects participated in this study, 22 of whom completed. Pharmacokinetic analyses of theophylline are based on 19 subjects (data for 2 subjects excluded due to vomiting post-dose and for 1 subject as an outlier. Pharmacokinetic analyses of quinine are based on 20 subjects (excluding the two who vomited).
The area under the plasma concentration versus time curve beginning from the first dose (time 0) to the last measurable concentration (time t), as calculated by the linear trapezoidal method.
Outcome measures
| Measure |
Theophylline Alone
n=19 Participants
At 7am on Day 1 after a fast of at least 10 hours, all subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration)followed by a 4-day washout period.
|
Quinine Alone
n=20 Participants
On Day 5 in the afternoon, dosing of quinine sulfate (2 x 324 mg capsules) was initiated and continued every 8 hours without regard to meals through Day 11.
|
Theophylline in the Presence of Quinine
n=19 Participants
At 7am on Day 12 after a fast of at least 10 hours, subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration) and quinine sulfate (2 x 324 mg capsules).
|
Quinine in the Presence of Theophylline
n=20 Participants
At 7am on Day 12 after a fast of at least 10 hours, subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration) and quinine sulfate (2 x 324 mg capsules).
|
|---|---|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
|
103.47 ug-hr/mL
Standard Deviation 35.82
|
45.17 ug-hr/mL
Standard Deviation 11.41
|
92.72 ug-hr/mL
Standard Deviation 31.17
|
51.68 ug-hr/mL
Standard Deviation 13.11
|
PRIMARY outcome
Timeframe: Serial pharmacokinetic blood samples for theophylline collected on Days 1 and 12 before dosing and for 48 hours post-dose.Population: A total of 24 healthy adult male subjects participated in this study, 22 of whom completed. Pharmacokinetic analyses of theophylline are based on 19 subjects (data for 2 subjects excluded due to vomiting post-dose and for 1 subject as an outlier. Pharmacokinetic analyses of quinine are based on 20 subjects (excluding the two who vomited).
The area under the plasma concentration versus time curve from time 0 to infinity. AUC(0-∞)was calculated as the sum of the AUC(0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant.
Outcome measures
| Measure |
Theophylline Alone
n=19 Participants
At 7am on Day 1 after a fast of at least 10 hours, all subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration)followed by a 4-day washout period.
|
Quinine Alone
n=19 Participants
On Day 5 in the afternoon, dosing of quinine sulfate (2 x 324 mg capsules) was initiated and continued every 8 hours without regard to meals through Day 11.
|
Theophylline in the Presence of Quinine
At 7am on Day 12 after a fast of at least 10 hours, subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration) and quinine sulfate (2 x 324 mg capsules).
|
Quinine in the Presence of Theophylline
At 7am on Day 12 after a fast of at least 10 hours, subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration) and quinine sulfate (2 x 324 mg capsules).
|
|---|---|---|---|---|
|
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)].
|
108.21 ug-hr/mL
Standard Deviation 37.33
|
96.88 ug-hr/mL
Standard Deviation 31.95
|
—
|
—
|
SECONDARY outcome
Timeframe: 5 hours - measured 1 hour pre-dose and then at 4 hours after the morning dose on Day 11The QT interval assesses cardiac repolarization and risk for arrhythmias. It is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. QTc is the QT interval corrected for heartrate.
Outcome measures
| Measure |
Theophylline Alone
n=23 Participants
At 7am on Day 1 after a fast of at least 10 hours, all subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration)followed by a 4-day washout period.
|
Quinine Alone
n=23 Participants
On Day 5 in the afternoon, dosing of quinine sulfate (2 x 324 mg capsules) was initiated and continued every 8 hours without regard to meals through Day 11.
|
Theophylline in the Presence of Quinine
At 7am on Day 12 after a fast of at least 10 hours, subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration) and quinine sulfate (2 x 324 mg capsules).
|
Quinine in the Presence of Theophylline
At 7am on Day 12 after a fast of at least 10 hours, subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration) and quinine sulfate (2 x 324 mg capsules).
|
|---|---|---|---|---|
|
Electrocardiogram (ECG) Evaluation of the Maximum QT Interval Corrected for Heartrate (QTc), Quinine Study Day 11.
|
453.33 msec
|
451.33 msec
|
—
|
—
|
SECONDARY outcome
Timeframe: 5 hours - measured 1 hour pre-dose and then at 4 hours post-dose on Day 12The QT interval assesses cardiac repolarization and risk for arrhythmias. It is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. QTc is the QT interval corrected for heartrate.
Outcome measures
| Measure |
Theophylline Alone
n=22 Participants
At 7am on Day 1 after a fast of at least 10 hours, all subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration)followed by a 4-day washout period.
|
Quinine Alone
n=22 Participants
On Day 5 in the afternoon, dosing of quinine sulfate (2 x 324 mg capsules) was initiated and continued every 8 hours without regard to meals through Day 11.
|
Theophylline in the Presence of Quinine
At 7am on Day 12 after a fast of at least 10 hours, subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration) and quinine sulfate (2 x 324 mg capsules).
|
Quinine in the Presence of Theophylline
At 7am on Day 12 after a fast of at least 10 hours, subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80mg/15ml concentration) and quinine sulfate (2 x 324 mg capsules).
|
|---|---|---|---|---|
|
Electrocardiogram (ECG) Evaluation of the Maximum QT Interval Corrected for Heartrate (QTc), Theophylline Co-administered With Quinine, Study Day 12.
|
452 msec
|
455.33 msec
|
—
|
—
|
Adverse Events
Theophylline Alone
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Quinine Alone
Serious events: 1 serious events
Other events: 22 other events
Deaths: 0 deaths
Theophylline Co-administered With Quinine
Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Theophylline Alone
At 7am on Day 1 after a fast of at least 10 hours, all subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80 mg/15 ml)followed by a 4 day washout period
|
Quinine Alone
On Day 5 in the afternoon, dosing of quinine sulfate (2 x 324 mg capsules) was initiated and continued every 8 hours without regard to meals through Day 11
|
Theophylline Co-administered With Quinine
At 7am on Day 12 after a fast of at least 10 hours, subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80 mg/15 ml) and quinine sulfate (2 x 324 mg capsules).
|
|---|---|---|---|
|
General disorders
drug hypersensitivity
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
Other adverse events
| Measure |
Theophylline Alone
At 7am on Day 1 after a fast of at least 10 hours, all subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80 mg/15 ml)followed by a 4 day washout period
|
Quinine Alone
On Day 5 in the afternoon, dosing of quinine sulfate (2 x 324 mg capsules) was initiated and continued every 8 hours without regard to meals through Day 11
|
Theophylline Co-administered With Quinine
At 7am on Day 12 after a fast of at least 10 hours, subjects received a single dose of theophylline (300 mg as an immediate-release oral solution 80 mg/15 ml) and quinine sulfate (2 x 324 mg capsules).
|
|---|---|---|---|
|
Cardiac disorders
palpitations
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
Ear and labyrinth disorders
deafness
|
0.00%
0/24
|
8.3%
2/24 • Number of events 2
|
4.2%
1/24 • Number of events 1
|
|
Ear and labyrinth disorders
deafness bilateral
|
0.00%
0/24
|
8.3%
2/24 • Number of events 2
|
0.00%
0/24
|
|
Ear and labyrinth disorders
dysacusis
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
|
Ear and labyrinth disorders
ear discomfort
|
0.00%
0/24
|
29.2%
7/24 • Number of events 7
|
0.00%
0/24
|
|
Ear and labyrinth disorders
ear pain
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
|
Ear and labyrinth disorders
hearing impaired
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
|
Ear and labyrinth disorders
hypoacusis
|
0.00%
0/24
|
12.5%
3/24 • Number of events 3
|
0.00%
0/24
|
|
Ear and labyrinth disorders
tinnitus
|
0.00%
0/24
|
54.2%
13/24 • Number of events 13
|
0.00%
0/24
|
|
Gastrointestinal disorders
abdominal pain upper
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
|
Gastrointestinal disorders
diarrhea
|
4.2%
1/24 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
|
Gastrointestinal disorders
haematochezia
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
Gastrointestinal disorders
nausea
|
4.2%
1/24 • Number of events 1
|
20.8%
5/24 • Number of events 5
|
50.0%
12/24 • Number of events 12
|
|
Gastrointestinal disorders
retching
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
Gastrointestinal disorders
stomach discomfort
|
0.00%
0/24
|
8.3%
2/24 • Number of events 2
|
0.00%
0/24
|
|
Gastrointestinal disorders
vomiting
|
0.00%
0/24
|
0.00%
0/24
|
8.3%
2/24 • Number of events 2
|
|
Gastrointestinal disorders
chest discomfort
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
General disorders
chest pain
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
General disorders
chills
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
General disorders
feeling cold
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
General disorders
feeling hot
|
0.00%
0/24
|
8.3%
2/24 • Number of events 2
|
8.3%
2/24 • Number of events 2
|
|
General disorders
feeling jittery
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
|
General disorders
pallor
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
12.5%
3/24 • Number of events 3
|
|
General disorders
pyrexia
|
0.00%
0/24
|
8.3%
2/24 • Number of events 2
|
0.00%
0/24
|
|
Investigations
heart rate increased
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
|
Metabolism and nutrition disorders
anorexia
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
|
Musculoskeletal and connective tissue disorders
back pain
|
0.00%
0/24
|
0.00%
0/24
|
8.3%
2/24 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
musculoskeletal chest pain
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
myalgia
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
neck pain
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
Nervous system disorders
dizziness
|
8.3%
2/24 • Number of events 2
|
25.0%
6/24 • Number of events 6
|
37.5%
9/24 • Number of events 9
|
|
Nervous system disorders
dysgeusia
|
0.00%
0/24
|
12.5%
3/24 • Number of events 3
|
0.00%
0/24
|
|
Nervous system disorders
headache
|
4.2%
1/24 • Number of events 1
|
8.3%
2/24 • Number of events 2
|
37.5%
9/24 • Number of events 9
|
|
Nervous system disorders
paraesthesia
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
|
Nervous system disorders
syncope
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
12.5%
3/24 • Number of events 3
|
|
Nervous system disorders
tremor
|
0.00%
0/24
|
0.00%
0/24
|
8.3%
2/24 • Number of events 2
|
|
Psychiatric disorders
confusional state
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
|
Psychiatric disorders
depressed mood
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
|
Psychiatric disorders
disorientation
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
|
Psychiatric disorders
restlessness
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
Psychiatric disorders
thinking abnormal
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
|
Renal and urinary disorders
urinary hesitation
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
|
Respiratory, thoracic and mediastinal disorders
haemoptysis
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
pharyngolaryngeal pain
|
0.00%
0/24
|
8.3%
2/24 • Number of events 2
|
0.00%
0/24
|
|
Skin and subcutaneous tissue disorders
drug eruption
|
0.00%
0/24
|
0.00%
0/24
|
8.3%
2/24 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
hyperhidrosis
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
|
Skin and subcutaneous tissue disorders
rash
|
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