Trial Outcomes & Findings for Drug-Drug Interaction Study of Qualaquin and Midazolam (NCT NCT00785486)
NCT ID: NCT00785486
Last Updated: 2012-08-31
Results Overview
Maximum serum concentration(Cmax)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Day 1 (Midazolam Alone), Day 9 (Qualaquin (quinine) Alone), Day 10 Midazolam with Qualaquin (quinine)
Results posted on
2012-08-31
Participant Flow
Participant milestones
| Measure |
Qualaquin (Quinine) And Midazolam Alone And In Combination
All pharmacokinetic studies were begun after a fast of at least 10 hours. On day 1 all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times sufficient to define the baseline kinetics of midazolam and 1-hydroxy-midazolam. After a 3 day washout period, on the morning of day 4, all participants began a regimen of 324 mg of quinine sulfate orally every 8 hours for a total of 21 doses. On day 9 after taking Qualaquin (quinine) for 5 days according to the stated regimen all participants took their usual dose of Qualaquin (quinine). Blood was drawn sufficient to characterize the steady state kinetics of quinine. On day 10 after taking Qualaquin (quinine) for 6 days according to the stated regimen, all participants took their usual dose of Qualaquin (quinine) with an oral dose of midazolam 2 mg. Blood was drawn sufficient to characterize the steady state kinetics of quinine and the kinetics of midazolam and 1-hydroxy-midazolam in the presence of each other.
|
|---|---|
|
Midazolam Alone
STARTED
|
24
|
|
Midazolam Alone
COMPLETED
|
23
|
|
Midazolam Alone
NOT COMPLETED
|
1
|
|
3 Day Washout
STARTED
|
23
|
|
3 Day Washout
COMPLETED
|
23
|
|
3 Day Washout
NOT COMPLETED
|
0
|
|
Qualaquin Alone at Steady State
STARTED
|
23
|
|
Qualaquin Alone at Steady State
COMPLETED
|
23
|
|
Qualaquin Alone at Steady State
NOT COMPLETED
|
0
|
|
Midazolam With Qualaquin at Steady State
STARTED
|
23
|
|
Midazolam With Qualaquin at Steady State
COMPLETED
|
23
|
|
Midazolam With Qualaquin at Steady State
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Qualaquin (Quinine) And Midazolam Alone And In Combination
All pharmacokinetic studies were begun after a fast of at least 10 hours. On day 1 all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times sufficient to define the baseline kinetics of midazolam and 1-hydroxy-midazolam. After a 3 day washout period, on the morning of day 4, all participants began a regimen of 324 mg of quinine sulfate orally every 8 hours for a total of 21 doses. On day 9 after taking Qualaquin (quinine) for 5 days according to the stated regimen all participants took their usual dose of Qualaquin (quinine). Blood was drawn sufficient to characterize the steady state kinetics of quinine. On day 10 after taking Qualaquin (quinine) for 6 days according to the stated regimen, all participants took their usual dose of Qualaquin (quinine) with an oral dose of midazolam 2 mg. Blood was drawn sufficient to characterize the steady state kinetics of quinine and the kinetics of midazolam and 1-hydroxy-midazolam in the presence of each other.
|
|---|---|
|
Midazolam Alone
Withdrawal by Subject
|
1
|
Baseline Characteristics
Drug-Drug Interaction Study of Qualaquin and Midazolam
Baseline characteristics by cohort
| Measure |
Qualaquin (Quinine) And Midazolam Alone And In Combination
n=24 Participants
All pharmacokinetic studies were begun after a fast of at least 10 hours. On day 1 all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times sufficient to define the baseline kinetics of midazolam and 1-hydroxy-midazolam. After a 3 day washout period, on the morning of day 4, all participants began a regimen of 324 mg of quinine sulfate orally every 8 hours for a total of 21 doses. On day 9 after taking Qualaquin (quinine) for 5 days according to the stated regimen all participants took their usual dose of Qualaquin (quinine). Blood was drawn sufficient to characterize the steady state kinetics of quinine. On day 10 after taking Qualaquin (quinine) for 6 days according to the stated regimen, all participants took their usual dose of Qualaquin (quinine) with an oral dose of midazolam 2 mg. Blood was drawn sufficient to characterize the steady state kinetics of quinine and the kinetics of midazolam and 1-hydroxy-midazolam in the presence of each other.
|
|---|---|
|
Age Continuous
|
31.1 years
STANDARD_DEVIATION 5.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 (Midazolam Alone), Day 9 (Qualaquin (quinine) Alone), Day 10 Midazolam with Qualaquin (quinine)Population: per protocol
Maximum serum concentration(Cmax)
Outcome measures
| Measure |
Midazolam - Midazolam Alone
n=23 Participants
On day 1 after a fast of at least 10 hours all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours to determine the baseline Cmax for midazolam.
|
1-Hydroxy-Midazolam - Midazolam Alone
n=23 Participants
On day 1 after a fast of at least 10 hours all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours to determine the baseline Cmax for 1-hydroxy-midazolam, the primary metabolite of midazolam
|
Quinine - Qualaquin(Quinine) Alone
n=23 Participants
On the morning of day 9 after taking Qualaquin(quinine)capsules 324 mg orally every 8 hours for the prior 5 days, and following a fast of at least 10 hours all study participants received their usual morning dose of Qualaquin (quinine)324 mg. Blood was drawn at times 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, and 7.917 hours to determine the steady state Cmax for Qualaquin (quinine) at this dose.
|
Midazolam - Midazolam With Qualaquin(Quinine)
n=23 Participants
On the morning of day 10, after a fast of at least 10 hours all study participants received an oral dose of both midazolam 2 mg and Qualaquin(quinine)324 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917. 12, 15 and 24 hours to determine Cmax for midazolam in the presence of Qualaquin (qunine)at steady state.
|
1-Hydroxy-Midazolam -Midazolam With Qualaquin(Quinine)
n=23 Participants
On the morning of day 10, after a fast of at least 10 hours all study participants received an oral dose of both midazolam 2 mg and Qualaquin(quinine)324 mg concurrently. On day 1 after a fast of at least 10 hours all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours to determine the Cmax for 1-hydroxy-midazolam in the presence of Qualaquin (quinine) at steady state.
|
Quinine - Qualaquin (Quinine) With Midazolam
n=23 Participants
On the morning of day 10 after taking Qualaquin (quinine)capsules 324 mg orally every 8 hours for the prior 6 days, and following a fast of at least 10 hours all study participants co-ingested oral dose s of midazolam 2 mg and their usual morning dose of Qualaquin (quinine)324 mg. Blood was drawn at times 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, and 7.917 hours to determine the steady state Cmax for Qualaquin (quinine)in the presence of midazolam.
|
|---|---|---|---|---|---|---|
|
Maximum Serum Concentration (Cmax)
|
12.0435 ng/ml
Standard Deviation 3.53669
|
4.6907 ng/ml
Standard Deviation 2.17605
|
4432.4089 ng/ml
Standard Deviation 678.36810
|
12.5585 ng/ml
Standard Deviation 3.51110
|
4.8605 ng/ml
Standard Deviation 1.82141
|
4399.7690 ng/ml
Standard Deviation 671.04523
|
PRIMARY outcome
Timeframe: Days 1 and 10 at 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hoursPopulation: by protocol
Area under the concentration time curve(AUC 0-t) calculated by the linear trapezoidal method from time 0 to 24 hours, for Midazolam and 1-hydroxy-midazolam on day 1 (midazolam alone) and day 10 (midazolam with Qualaquin -(quinine) at steady state to determine if a significant drug interaction occurs between midazolam and quinine
Outcome measures
| Measure |
Midazolam - Midazolam Alone
n=23 Participants
On day 1 after a fast of at least 10 hours all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours to determine the baseline Cmax for midazolam.
|
1-Hydroxy-Midazolam - Midazolam Alone
n=23 Participants
On day 1 after a fast of at least 10 hours all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours to determine the baseline Cmax for 1-hydroxy-midazolam, the primary metabolite of midazolam
|
Quinine - Qualaquin(Quinine) Alone
n=23 Participants
On the morning of day 9 after taking Qualaquin(quinine)capsules 324 mg orally every 8 hours for the prior 5 days, and following a fast of at least 10 hours all study participants received their usual morning dose of Qualaquin (quinine)324 mg. Blood was drawn at times 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, and 7.917 hours to determine the steady state Cmax for Qualaquin (quinine) at this dose.
|
Midazolam - Midazolam With Qualaquin(Quinine)
n=23 Participants
On the morning of day 10, after a fast of at least 10 hours all study participants received an oral dose of both midazolam 2 mg and Qualaquin(quinine)324 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917. 12, 15 and 24 hours to determine Cmax for midazolam in the presence of Qualaquin (qunine)at steady state.
|
1-Hydroxy-Midazolam -Midazolam With Qualaquin(Quinine)
On the morning of day 10, after a fast of at least 10 hours all study participants received an oral dose of both midazolam 2 mg and Qualaquin(quinine)324 mg concurrently. On day 1 after a fast of at least 10 hours all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours to determine the Cmax for 1-hydroxy-midazolam in the presence of Qualaquin (quinine) at steady state.
|
Quinine - Qualaquin (Quinine) With Midazolam
On the morning of day 10 after taking Qualaquin (quinine)capsules 324 mg orally every 8 hours for the prior 6 days, and following a fast of at least 10 hours all study participants co-ingested oral dose s of midazolam 2 mg and their usual morning dose of Qualaquin (quinine)324 mg. Blood was drawn at times 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, and 7.917 hours to determine the steady state Cmax for Qualaquin (quinine)in the presence of midazolam.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration Time Curve From Zero to T (AUC 0-t) for Midazolam and 1-hydroxy Midazolam at Baseline and With Qualaquin (Quinine) at Steady State.
|
30.076 ng•h/mL
Standard Deviation 10.1593
|
10.780 ng•h/mL
Standard Deviation 6.6534
|
27.242 ng•h/mL
Standard Deviation 6.5008
|
10.454 ng•h/mL
Standard Deviation 5.2714
|
—
|
—
|
PRIMARY outcome
Timeframe: Days 1 and 10 at 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hoursPopulation: per protocol
AUC inf for Midazolam and hydroxy-midazolam on day 1 (midazolam alone) and day 10 (midazolam with steady state Qualaquin(quinine)- the sum of AUC0-t plus the ratio of the last measured plasma concentration to the elimination rate constant to determine whether a significant drug interaction occurs between midazolam and quinine
Outcome measures
| Measure |
Midazolam - Midazolam Alone
n=23 Participants
On day 1 after a fast of at least 10 hours all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours to determine the baseline Cmax for midazolam.
|
1-Hydroxy-Midazolam - Midazolam Alone
n=23 Participants
On day 1 after a fast of at least 10 hours all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours to determine the baseline Cmax for 1-hydroxy-midazolam, the primary metabolite of midazolam
|
Quinine - Qualaquin(Quinine) Alone
n=23 Participants
On the morning of day 9 after taking Qualaquin(quinine)capsules 324 mg orally every 8 hours for the prior 5 days, and following a fast of at least 10 hours all study participants received their usual morning dose of Qualaquin (quinine)324 mg. Blood was drawn at times 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, and 7.917 hours to determine the steady state Cmax for Qualaquin (quinine) at this dose.
|
Midazolam - Midazolam With Qualaquin(Quinine)
n=23 Participants
On the morning of day 10, after a fast of at least 10 hours all study participants received an oral dose of both midazolam 2 mg and Qualaquin(quinine)324 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917. 12, 15 and 24 hours to determine Cmax for midazolam in the presence of Qualaquin (qunine)at steady state.
|
1-Hydroxy-Midazolam -Midazolam With Qualaquin(Quinine)
On the morning of day 10, after a fast of at least 10 hours all study participants received an oral dose of both midazolam 2 mg and Qualaquin(quinine)324 mg concurrently. On day 1 after a fast of at least 10 hours all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours to determine the Cmax for 1-hydroxy-midazolam in the presence of Qualaquin (quinine) at steady state.
|
Quinine - Qualaquin (Quinine) With Midazolam
On the morning of day 10 after taking Qualaquin (quinine)capsules 324 mg orally every 8 hours for the prior 6 days, and following a fast of at least 10 hours all study participants co-ingested oral dose s of midazolam 2 mg and their usual morning dose of Qualaquin (quinine)324 mg. Blood was drawn at times 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, and 7.917 hours to determine the steady state Cmax for Qualaquin (quinine)in the presence of midazolam.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration Time Curve From Zero to Infinity (AUC Inf) for Midazolam and 1 Hydroxy Midazolam Before (Day 1) and After (Day 10) Qualaquin (Quinine).
|
31.324 ng·h/mL
Standard Deviation 10.0930
|
11.669 ng·h/mL
Standard Deviation 7.4340
|
28.771 ng·h/mL
Standard Deviation 6.8081
|
11.447 ng·h/mL
Standard Deviation 5.8587
|
—
|
—
|
PRIMARY outcome
Timeframe: Days 9 and 10 at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, and 7.917 hoursPopulation: per protocol
Qualaquin (quinine) - AUC tau alone at steady state (day 9) and in the presence of coadministered midazolam 2 mg (day 10) over the dosing interval (0 - 8 hours), as calculated by the linear trapezoidal method.
Outcome measures
| Measure |
Midazolam - Midazolam Alone
n=23 Participants
On day 1 after a fast of at least 10 hours all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours to determine the baseline Cmax for midazolam.
|
1-Hydroxy-Midazolam - Midazolam Alone
n=23 Participants
On day 1 after a fast of at least 10 hours all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours to determine the baseline Cmax for 1-hydroxy-midazolam, the primary metabolite of midazolam
|
Quinine - Qualaquin(Quinine) Alone
On the morning of day 9 after taking Qualaquin(quinine)capsules 324 mg orally every 8 hours for the prior 5 days, and following a fast of at least 10 hours all study participants received their usual morning dose of Qualaquin (quinine)324 mg. Blood was drawn at times 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, and 7.917 hours to determine the steady state Cmax for Qualaquin (quinine) at this dose.
|
Midazolam - Midazolam With Qualaquin(Quinine)
On the morning of day 10, after a fast of at least 10 hours all study participants received an oral dose of both midazolam 2 mg and Qualaquin(quinine)324 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917. 12, 15 and 24 hours to determine Cmax for midazolam in the presence of Qualaquin (qunine)at steady state.
|
1-Hydroxy-Midazolam -Midazolam With Qualaquin(Quinine)
On the morning of day 10, after a fast of at least 10 hours all study participants received an oral dose of both midazolam 2 mg and Qualaquin(quinine)324 mg concurrently. On day 1 after a fast of at least 10 hours all participants received a single oral dose of midazolam 2 mg. Blood was drawn at times 0, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours to determine the Cmax for 1-hydroxy-midazolam in the presence of Qualaquin (quinine) at steady state.
|
Quinine - Qualaquin (Quinine) With Midazolam
On the morning of day 10 after taking Qualaquin (quinine)capsules 324 mg orally every 8 hours for the prior 6 days, and following a fast of at least 10 hours all study participants co-ingested oral dose s of midazolam 2 mg and their usual morning dose of Qualaquin (quinine)324 mg. Blood was drawn at times 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, and 7.917 hours to determine the steady state Cmax for Qualaquin (quinine)in the presence of midazolam.
|
|---|---|---|---|---|---|---|
|
The Area Under the the Concentration Time Curve From Zero to Tau (0-8hrs) for Qualaquin (Quinine) AUC Tau Before and After Midazolam
|
30455.4 ng•h/mL
Standard Deviation 5028.27
|
30568.7 ng•h/mL
Standard Deviation 4851.10
|
—
|
—
|
—
|
—
|
Adverse Events
Midazolam Alone
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Qualaquin (Quinine) Alone
Serious events: 0 serious events
Other events: 27 other events
Deaths: 0 deaths
Midazolam With Qualaquin (Quinine) Together
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 |
Midazolam Alone
n=24 participants at risk
Adverse effects on day 1 after participants received 2mg of midazolam syrup orally.
|
Qualaquin (Quinine) Alone
n=23 participants at risk
Adverse effects(ADR)while taking Qualaquin(quinine)324 mg alone orally every 8 hours on days 4-11. Results are reported as total for the 7 day period.
|
Midazolam With Qualaquin (Quinine) Together
n=23 participants at risk
Adverse effects reported on day 10 after participants received 2 mg of midazolam syrup and 324 mg of Qualaquin(quinine)orally.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/23
|
43.5%
10/23 • Number of events 10
|
13.0%
3/23 • Number of events 3
|
|
Ear and labyrinth disorders
Tinnitis
|
4.3%
1/23 • Number of events 1
|
17.4%
4/23 • Number of events 4
|
0.00%
0/23
|
|
General disorders
Feeling Hot
|
0.00%
0/23
|
17.4%
4/23 • Number of events 4
|
0.00%
0/23
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/23
|
13.0%
3/23 • Number of events 3
|
4.3%
1/23 • Number of events 1
|
|
Nervous system disorders
Tremor
|
0.00%
0/23
|
13.0%
3/23 • Number of events 3
|
0.00%
0/23
|
|
Ear and labyrinth disorders
Ear Discomfort
|
0.00%
0/23
|
13.0%
3/23 • Number of events 3
|
0.00%
0/23
|
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