Trial Outcomes & Findings for A Dose Proportionality Study of Quinine Sulfate Capsules Under Fasting Conditions (NCT NCT00726895)

NCT ID: NCT00726895

Last Updated: 2010-01-20

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 plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36 and 48 hours after drug administration.

Results posted on

2010-01-20

Participant Flow

Participant milestones

Participant milestones
Measure	Quinine Sulfate Capsules 1 x 324 mg Dose Then 2 x 324 mg Dose All subjects received each of the two study regimens (Treatment A - Quinine Sulfate 1 x 324 mg capsule, Treatment B - Quinine Sulfate 2 x 324 mg capsules) in a randomly assigned sequence of dosing periods, each followed by a washout period of 7 days.	Quinine Sulfate Capsules 2 x 324 mg Dose Then 1 x 324 mg Dose All subjects received each of the two study regimens (Treatment A - Quinine Sulfate 1 x 324 mg capsule, Treatment B - Quinine Sulfate 2 x 324 mg capsules) in a randomly assigned sequence of dosing periods, each followed by a washout period of 7 days.
First Intervention STARTED	12	12
First Intervention COMPLETED	12	12
First Intervention NOT COMPLETED	0	0
Washout Period of 7 Days STARTED	12	12
Washout Period of 7 Days COMPLETED	12	11
Washout Period of 7 Days NOT COMPLETED	0	1
Second Intervention STARTED	12	11
Second Intervention COMPLETED	12	11
Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Quinine Sulfate Capsules 1 x 324 mg Dose Then 2 x 324 mg Dose All subjects received each of the two study regimens (Treatment A - Quinine Sulfate 1 x 324 mg capsule, Treatment B - Quinine Sulfate 2 x 324 mg capsules) in a randomly assigned sequence of dosing periods, each followed by a washout period of 7 days.	Quinine Sulfate Capsules 2 x 324 mg Dose Then 1 x 324 mg Dose All subjects received each of the two study regimens (Treatment A - Quinine Sulfate 1 x 324 mg capsule, Treatment B - Quinine Sulfate 2 x 324 mg capsules) in a randomly assigned sequence of dosing periods, each followed by a washout period of 7 days.
Washout Period of 7 Days Withdrawal by Subject	0	1

Baseline Characteristics

A Dose Proportionality Study of Quinine Sulfate Capsules Under Fasting Conditions

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entire Study Population n=24 Participants All subjects received each of the two study regimens in a randomly assigned sequence of dosing periods. On the mornings of Day 1 and Day 8, each subject received either one Quinine Sulfate 324 mg capsule or two Quinine Sulfate 324 mg capsules following an overnight fast of at least 10 hours.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	33 years STANDARD_DEVIATION 13.9 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 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	0 Participants n=5 Participants
Race (NIH/OMB) White	23 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

PRIMARY outcome

Timeframe: serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36 and 48 hours after drug administration.

Population: Plasma concentration data for 23 of the 24 enrolled subjects were used in the statistical analysis. Subject number 12 dropped from the study prior to period II (Treatment A) dosing. Treatment A, Dose Adjusted to 2 x 324 mg was a statistical adjustment only used to evaluate for dose proportionality.

The maximum or peak concentration that the drug reaches in the plasma.

Outcome measures

Outcome measures
Measure	Treatment A - Quinine Sulfate Capsules (1 x 324 mg Dose) n=23 Participants Each subject received one capsule of Quinine Sulfate 324 mg after an overnight fast of at least 10 hours.	Treatment A, Dose Adjusted to 2 x 324 mg n=23 Participants This group was a statistical adjustment only. Treatment A (Quinine Sulfate 1 x 324 mg Capsule) Dose Adjusted to 2 x 324 mg was used to evaluate for dose proportionality.	Treatment B - Quinine Sulfate Capsules (2 x 324 mg Dose) n=23 Participants Each subject received two capsules of Quinine Sulfate 324 mg after an overnight fast of at least 10 hours.
Maximum Plasma Concentration (Cmax)	2,118.35 ng/mL Standard Deviation 517.79	4,236.70 ng/mL Standard Deviation 1,035.58	3,242.92 ng/mL Standard Deviation 685.80

PRIMARY outcome

The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable concentration (t), as calculated by the linear trapezoidal rule.

Outcome measures

Outcome measures
Measure	Treatment A - Quinine Sulfate Capsules (1 x 324 mg Dose) n=23 Participants Each subject received one capsule of Quinine Sulfate 324 mg after an overnight fast of at least 10 hours.	Treatment A, Dose Adjusted to 2 x 324 mg n=23 Participants This group was a statistical adjustment only. Treatment A (Quinine Sulfate 1 x 324 mg Capsule) Dose Adjusted to 2 x 324 mg was used to evaluate for dose proportionality.	Treatment B - Quinine Sulfate Capsules (2 x 324 mg Dose) n=23 Participants Each subject received two capsules of Quinine Sulfate 324 mg 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)]	31,951.03 ng-hr/mL Standard Deviation 10,428.59	63,902.06 ng-hr/mL Standard Deviation 20,857.17	56,198.20 ng-hr/mL Standard Deviation 15,683.25

PRIMARY outcome

The 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 plasma concentration to the elimination rate constant.

Outcome measures

Outcome measures
Measure	Treatment A - Quinine Sulfate Capsules (1 x 324 mg Dose) n=23 Participants Each subject received one capsule of Quinine Sulfate 324 mg after an overnight fast of at least 10 hours.	Treatment A, Dose Adjusted to 2 x 324 mg n=23 Participants This group was a statistical adjustment only. Treatment A (Quinine Sulfate 1 x 324 mg Capsule) Dose Adjusted to 2 x 324 mg was used to evaluate for dose proportionality.	Treatment B - Quinine Sulfate Capsules (2 x 324 mg Dose) n=23 Participants Each subject received two capsules of Quinine Sulfate 324 mg after an overnight fast of at least 10 hours.
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]	35,199.28 ng-hr/mL Standard Deviation 12,678.60	70,398.56 ng-hr/mL Standard Deviation 25,357.19	61,570.10 ng-hr/mL Standard Deviation 19,295.34

Adverse Events

Treatment A - Quinine Sulfate Capsules 1 x 324 mg Dose

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Treatment B - Quinine Sulfate Capsules 2 x 324 mg Dose

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical 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

Measure	Treatment A - Quinine Sulfate Capsules 1 x 324 mg Dose n=23 participants at risk All subjects received each of the two study regimens (Treatment A - Quinine Sulfate 1 x 324 mg capsule, Treatment B - Quinine Sulfate 2 x 324 mg capsules) in a randomly assigned sequence of dosing periods, each followed by a washout period of 7 days.	Treatment B - Quinine Sulfate Capsules 2 x 324 mg Dose n=24 participants at risk All subjects received each of the two study regimens (Treatment A - Quinine Sulfate 1 x 324 mg capsule, Treatment B - Quinine Sulfate 2 x 324 mg capsules) in a randomly assigned sequence of dosing periods, each followed by a washout period of 7 days.
Metabolism and nutrition disorders Loss of appetite	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Gastrointestinal disorders Diarrhea	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Nervous system disorders Dizziness	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	12.5% 3/24 • Number of events 3 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Reproductive system and breast disorders Dysmenorrhea	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
General disorders Generalized pain	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Nervous system disorders Headache	8.7% 2/23 • Number of events 2 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	8.3% 2/24 • Number of events 2 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Musculoskeletal and connective tissue disorders Joint injury	4.3% 1/23 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	0.00% 0/24 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Musculoskeletal and connective tissue disorders Myalgia in extremities	4.3% 1/23 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	0.00% 0/24 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Gastrointestinal disorders Nausea	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	12.5% 3/24 • Number of events 3 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Skin and subcutaneous tissue disorders Night Sweats	4.3% 1/23 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	0.00% 0/24 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
General disorders Pain in extremity	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
General disorders Pallor	4.3% 1/23 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal - Sore throat	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
General disorders Rigors	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Gastrointestinal disorders Stomach discomfort	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Skin and subcutaneous tissue disorders Sweating increased	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Nervous system disorders Syncope	8.7% 2/23 • Number of events 2 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	0.00% 0/24 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Nervous system disorders Tinnitus	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Respiratory, thoracic and mediastinal disorders Tonsillitis	0.00% 0/23 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	4.2% 1/24 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	4.3% 1/23 • Number of events 1 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.	0.00% 0/24 24 subjects were enrolled in this study. One subject dropped out of the study prior to receiving both interventions. 23 subjects were administered the Quinine Sulfate 1 x 324 mg capsule dose and 24 subjects were admistered the Quinine Sulfate 2 x 324 mg capusle dose.