A Relative Bioavailability Study of Quinine Sulfate Capsules Under Fasting and Fed Conditions - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Bio-availability Study; Intervention Model: Crossover Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Basic Science
Condition:	Healthy
Interventions:	Drug: Quinine Sulfate Capsules 324 mg Drug: Quinine Sulphate Tablets 300 mg

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Treatment Sequence ABC	All subjects received each of the three study regimens (Treatment A - Quinine Sulfate Capsules 324 mg under fasting conditions, Treatment B - Quinine Sulphate Tablets 300 mg under fasting conditions and Treatment C - Quinine Sulfate Capsules 324 mg under fed conditions) in a randomly assigned sequence of dosing periods, each followed by a washout period of 7 days.
Treatment Sequence BCA	All subjects received each of the three study regimens (Treatment A - Quinine Sulfate Capsules 324 mg under fasting conditions, Treatment B - Quinine Sulphate Tablets 300 mg under fasting conditions and Treatment C - Quinine Sulfate Capsules 324 mg under fed conditions) in a randomly assigned sequence of dosing periods, each followed by a washout period of 7 days.
Treatment Sequence CAB	All subjects received each of the three study regimens (Treatment A - Quinine Sulfate Capsules 324 mg under fasting conditions, Treatment B - Quinine Sulphate Tablets 300 mg under fasting conditions and Treatment C - Quinine Sulfate Capsules 324 mg under fed conditions) in a randomly assigned sequence of dosing periods, each followed by a washout period of 7 days.

Participant Flow for 5 periods

Period 1: Period I

	Treatment Sequence ABC	Treatment Sequence BCA	Treatment Sequence CAB
STARTED	9	9	9
COMPLETED	9	9	9
NOT COMPLETED	0	0	0

Period 2: Washout Period A

	Treatment Sequence ABC	Treatment Sequence BCA	Treatment Sequence CAB
STARTED	9	9	9
COMPLETED	9	9	8 ^[1]
NOT COMPLETED	0	0	1
Adverse Event	0	0	1

[1]	positive pregnancy test - recorded as an adverse event

Period 3: Period II

	Treatment Sequence ABC	Treatment Sequence BCA	Treatment Sequence CAB
STARTED	9	9	8
COMPLETED	9	9	8
NOT COMPLETED	0	0	0

Period 4: Washout Period B

	Treatment Sequence ABC	Treatment Sequence BCA	Treatment Sequence CAB
STARTED	9	9	8
COMPLETED	9	9	7 ^[1]
NOT COMPLETED	0	0	1
Withdrawal by Subject	0	0	1

[1]	personal reasons

Period 5: Period III

	Treatment Sequence ABC	Treatment Sequence BCA	Treatment Sequence CAB
STARTED	9	9	7
COMPLETED	9	9	7
NOT COMPLETED	0	0	0

Baseline Characteristics

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Reporting Groups

	Description
Entire Study Population	All subjects received each of the three study regimens (Treatment A - Quinine Sulfate Capsules 324 mg under fasting conditions, Treatment B - Quinine Sulphate Tablets 300 mg under fasting conditions and Treatment C - Quinine Sulfate Capsules 324 mg under Fed conditions) in a randomly assigned sequence of dosing periods, each followed by a washout period of 7 days.

Baseline Measures

	Entire Study Population
Number of Participants [units: participants]	27
Age [units: participants]
<=18 years	0
Between 18 and 65 years	27
>=65 years	0
Age [units: years] Mean ± Standard Deviation	24.11 ± 8.87
Gender [units: participants]
Female	15
Male	12
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	0
White	26
More than one race	0
Unknown or Not Reported	1
Ethnicity (NIH/OMB) [units: participants]
Hispanic or Latino	1
Not Hispanic or Latino	26
Unknown or Not Reported	0

Outcome Measures

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1. Primary:

Maximum Plasma Concentration (Cmax) [ Time Frame: serial pharmacokinetic blood samples drawn within one hour prior to dosing (hour 0) 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 dose administration. ]

Measure Type	Primary
Measure Title	Maximum Plasma Concentration (Cmax)
Measure Description	The maximum or peak concentration that the drug reaches in the plasma.
Time Frame	serial pharmacokinetic blood samples drawn within one hour prior to dosing (hour 0) 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 dose administration.
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data for 26 of the 27 subjects were used in the statistical analysis for Treatments A and C. The data for one subject, who dropped from the study prior to period III dosing (Treatment B), was included in the comparison of Treatments A versus C. Treatment A, Dose Adjusted to 300 mg was used to evaluate for dose proportionality.

Reporting Groups

	Description
Treatment A - Quinine Sulfate 324 mg Caps, Fasting Conditions	Each subject received one capsule of Quinine Sulfate 324 mg after an overnight fast of at least 10 hours.
Treatment A, Dose Adjusted to 300 mg	This group was a statistical adjustment only. Treatment A (Quinine Sulfate 1 x 324 mg Capsule) Dose Adjusted to 300 mg was used to evaluate for dose proportionality.
Treatment B- Quinine Sulphate 300 mg Tabs, Fasting Conditions	Each subject received one tablet of Quinine Sulphate 300 mg after an overnight fast of at least 10 hours.
Treatment C - Quinine Sulfate 324 mg Caps, Fed Conditions	Each subject received one capsule of Quinine Sulfate 324 mg thirty minutes after the initiation of a standardized, high-fat breakfast following an overnight fast.

Measured Values

	Treatment A - Quinine Sulfate 324 mg Caps, Fasting Conditions	Treatment A, Dose Adjusted to 300 mg	Treatment B- Quinine Sulphate 300 mg Tabs, Fasting Conditions	Treatment C - Quinine Sulfate 324 mg Caps, Fed Conditions
Number of Participants Analyzed [units: participants]	26	26	25	26
Maximum Plasma Concentration (Cmax) [units: ng/mL] Mean ± Standard Deviation	2,246.58 ± 594.69	2,080.18 ± 550.64	2,278.46 ± 547.79	2,539.94 ± 740.19

No statistical analysis provided for Maximum Plasma Concentration (Cmax)

2. Primary:

Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] [ Time Frame: serial pharmacokinetic blood samples drawn within one hour prior to dosing (hour 0) 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 dose administration. ]

Measure Type	Primary
Measure Title	Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
Measure Description	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.
Time Frame	serial pharmacokinetic blood samples drawn within one hour prior to dosing (hour 0) 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 dose administration.
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data for 26 of the 27 subjects were used in the statistical analysis for Treatments A and C. The data for one subject, who dropped from the study prior to period III dosing (Treatment B), was included in the comparison of Treatments A versus C. Treatment A, Dose Adjusted to 300 mg was used to evaluate for dose proportionality.

Reporting Groups

	Description
Treatment A - Quinine Sulfate 324 mg Caps, Fasting Conditions	Each subject received one capsule of Quinine Sulfate 324 mg after an overnight fast of at least 10 hours.
Treatment A, Dose Adjusted to 300 mg	This group was a statistical adjustment only. Treatment A (Quinine Sulfate 1 x 324 mg Capsule) Dose Adjusted to 300 mg was used to evaluate for dose proportionality.
Treatment B- Quinine Sulphate 300 mg Tabs, Fasting Conditions	Each subject received one tablet of Quinine Sulphate 300 mg after an overnight fast of at least 10 hours.
Treatment C - Quinine Sulfate 324 mg Caps, Fed Conditions	Each subject received one capsule of Quinine Sulfate 324 mg 30 minutes after the initiation of a standardized, high-fat breakfast following an overnight fast.

Measured Values

	Treatment A - Quinine Sulfate 324 mg Caps, Fasting Conditions	Treatment A, Dose Adjusted to 300 mg	Treatment B- Quinine Sulphate 300 mg Tabs, Fasting Conditions	Treatment C - Quinine Sulfate 324 mg Caps, Fed Conditions
Number of Participants Analyzed [units: participants]	26	26	25	26
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] [units: ng-hr/mL] Mean ± Standard Deviation	32,689.35 ± 8,667.79	30,267.96 ± 8,025.76	31,689.32 ± 9,549.17	34,729.00 ± 11,625.99

No statistical analysis provided for Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]

3. Primary:

Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] [ Time Frame: serial pharmacokinetic blood samples drawn within one hour prior to dosing (hour 0) 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 dose administration. ]

Measure Type	Primary
Measure Title	Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
Measure Description	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.
Time Frame	serial pharmacokinetic blood samples drawn within one hour prior to dosing (hour 0) 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 dose administration.
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data for 26 of the 27 subjects were used in the statistical analysis for Treatments A and C. The data for one subject, who dropped from the study prior to period III dosing (Treatment B), was included in the comparison of Treatments A versus C. Treatment A, Dose Adjusted to 300 mg was used to evaluate for dose proportionality.

Reporting Groups

	Description
Treatment A - Quinine Sulfate 324 mg Caps, Fasting Conditions	Each subject received one capsule of Quinine Sulfate 324 mg after an overnight fast of at least 10 hours.
Treatment A, Dose Adjusted to 300 mg	This group was a statistical adjustment only. Treatment A (Quinine Sulfate 1 x 324 mg Capsule) Dose Adjusted to 300 mg was used to evaluate for dose proportionality.
Treatment B- Quinine Sulphate 300 mg Tabs, Fasting Conditions	Each subject received one tablet of Quinine Sulphate 300 mg after an overnight fast of at least 10 hours.
Treatment C - Quinine Sulfate 324 mg Caps, Fed Conditions	Each subject received one capsule of Quinine Sulfate 324 mg thirty minutes after the initiation of a standardized, high-fat breakfast following an overnight fast.

Measured Values

	Treatment A - Quinine Sulfate 324 mg Caps, Fasting Conditions	Treatment A, Dose Adjusted to 300 mg	Treatment B- Quinine Sulphate 300 mg Tabs, Fasting Conditions	Treatment C - Quinine Sulfate 324 mg Caps, Fed Conditions
Number of Participants Analyzed [units: participants]	26	26	25	26
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] [units: ng-hr/mL] Mean ± Standard Deviation	36,132.35 ± 11,054.19	33,456.04 ± 10,235.39	34,410.28 ± 11,636.62	37,550.81 ± 14,809.14

No statistical analysis provided for Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Medical Director
Organization: Mutual Pharmaceutical Company, Inc.
phone: 215-697-1743
e-mail: clinicaltrials@urlmutual.com

No publications provided

Responsible Party:	Matthew Davis, MD, Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier:	NCT00727272 History of Changes
Other Study ID Numbers:	RA3-085
Study First Received:	July 30, 2008
Results First Received:	November 24, 2009
Last Updated:	January 11, 2010
Health Authority:	United States: Food and Drug Administration