Comparison Bioavailability Study of Quinine Sulfate in Chocolate Pudding

Study Overview
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Brief Summary
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This is an open label randomized single dose two-way crossover study to compare the bioavailability of a single oral dose of quinine sulfate 648 mg(2 x 324 mg) when mixed with 120 ml of chocolate pudding relative to the same dose given as two intact capsules.

Detailed Description
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Prior studies have shown that intact quinine sulfate capsules can be taken without regard for food. This is an open label randomized single dose two-way crossover study to compare the bioavailability of a single oral dose of quinine sulfate 648mg(2 x 324 mg capsules) when opened and mixed with 120 ml of chocolate pudding relative to the same dose given as two intact capsules. Eighteen healthy adult subjects will be enrolled. Following a fast of at least 10 hours subjects will be randomized to receive either 648 mg of quinine sulfate as the intact capsules or opened mixed in 120ml of chocolate pudding. Following a washout period of at least 7 days all subjects will be given the alternate dose under similar conditions. Following each dose, blood samples will be collected at times sufficient to determine the difference in bioavailability (if any) between the two methods of drug administration. In addition patients will be monitored for any adverse events including Electrocardiogram (EKG) changes (at baseline and 4 hours after each dose).

Official Title
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A Comparison of the Bioavailability of Quinine Sulfate Capsules Following a 648 mg Dose When Mixed in Chocolate Pudding Relative to That With Intact Capsules in Healthy Adults Under Fasting Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: quinine sulfate
* Drug: quinine sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy nonsmoking adults with hemoglobin at least 12 g/dl. Males at least 52 kg, females at least 45kg with body mass index in the normal range, females must be chemically or surgically sterile or postmenopausal (amenorrhea at least 2years) Exclusion Criteria: Pregnant or lactating Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) Recent (1-year) history or evidence of alcoholism or drug abuse History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease, myasthenia gravis, optic neuritis or Glucose-6-phosphate dehydrogenase (G6PD) deficiency Prolonged corrected QT interval(QTc) on Electrocardiogram(EKG) at screening -males >430 msec, females >450 msec. PR interval on EKG >200 msec at screening or prior to dose in either dosing period Subjects who have used any drugs or substances known to inhibit or induce cytochrome (CYP) P450 enzymes and/or P-glycoprotein (P-gp) within 30 days prior to the first dose and throughout the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Single dose intact capsules 2 x 324 mg | Drug: quinine sulfate<br>* 2 x 324 mg capsules (648 mg)<br>* Other names: Qualaquin;|
| Experimental: 2<br>Single dose contents of two capsules (2 x 324 mg) opened and mixed in 120 mL of chocolate pudding | Drug: quinine sulfate<br>* 2 x 324 mg capsules (648 mg)<br>* Other names: Qualaquin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | The highest concentration of drug in plasma after a dose. Measured to evaluate the bioequivalence of the two dosing methods | After dosing at time points 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, and 48 hours | 
| Area Under the Concentration Time Curve From Zero to t. (AUC 0-t) | The area under the plasma concentration versus time curve from zero to the last measurable plasma concentration as calculated by the linear trapezoidal method. Calculated to determine whether the 2 methods of administration are bioequivalent. | After dosing at time points 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, and 48 hours | 
| The Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity. (AUC Inf) | AUC inf is calculated as the sum of the AUC 0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant.It is calculated to evaluate the bioequivalence of the two dosing methods | After dosing at time points 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, and 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Bioequivalence, Pharmacokinetics