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

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Quinine Sulfate Capsules 324 mg
Drug: Quinine Sulphate Tablets 300 mg

Registration Number: NCT00727272

Lead Sponsor: Mutual Pharmaceutical Company, Inc.

Brief Summary: The purpose of this study is to evaluate and compare the relative bioavailability of Quinine Sulfate 324 mg capsules, manufactured by the Mutual Pharmaceutical Company, to Quinine Sulphate 300 mg tablets, manufactured by the Government Pharmaceutical Organization, Bangkok Metropolis, Thailand, after single oral dose administration under fasting conditions. An additional purpose of this study is to evaluate the effect of food on the Mutual Pharmaceutical Company product.

Detailed Description: The purpose of this study is to evaluate and compare the relative bioavailability of Quinine Sulfate 324 mg capsules, manufactured by the Mutual Pharmaceutical Company, to Quinine Sulphate 300 mg tablets, manufactured by the Government Pharmaceutical Organization, Bangkok Metropolis, Thailand, after single oral dose administration under fasting conditions. An additional purpose of this study is to evaluate the effect of food on the Mutual Pharmaceutical Company product.

Twenty-seven healthy, non-smoking, non-obese, male and female volunteers at least 18 years of age will be randomly assigned in crossover fashion to receive each of three dosing regimens in sequence with a 7 day washout period between dosing periods. In each of the three dosing periods, after a fast of at least 10 hours, subjects will receive one dose of one of the three test products (treatment A - quinine sulfate capsules 324 mg, treatment B - quinine sulphate tablets 300 mg, treatment C - quinine sulfate capsules 324 mg administered thirty minutes after the initiation of a standardized, high-fat breakfast). Subjects will fast for 4 hours after dosing. Blood samples will be drawn from all participants before dosing and for 48 hours post-dose at times sufficient to adequately define the pharmacokinetics of quinine sulfate under fed and fasting conditions and quinine sulphate under fasting conditions. Sitting blood pressure and heart rate will be obtained prior to dosing and at 1, 2, 4 and 12 hours post-dose and upon completion of the study. An electrocardiogram will be recorded at check-in and at 2, 4, 6, 12, and 24 hours post-dose. Subjects will be monitored throughout their participation in the study for adverse reactions.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

Inclusion Criteria

Screening Demographics: All volunteers selected for this study will be healthy men or women at least 18 years of age, inclusive, at the the time of dosing. The weight range will not exceed ± 20% for height and body frame as per Desirable Weights for Adults - 1983 Metropolitan Height and Weight Table
Screening procedures: Each volunteer will complete the screening process within 28 days prior to Period I dosing. Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed, and signed by each potential participant before full implementation of screening procedures.
Screening will include general observations, physical examination, demographics, medical and medication history, an electrocardiogram, sitting blood pressure and heart rate, respiratory rate and temperature. The physical examination will include an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems.
The screening clinical laboratory procedures will include:
HEMATOLOGY: hematocrit, hemoglobin, WBC count with differential, RBC count, platelet count
CLINICAL CHEMISTRY:serum creatinine, BUN, glucose, AST(GOT), ALT(GPT), albumin, total bilirubin, total protein, and alkaline phosphatase
HIV antibody and hepatitis B surface antigen screens
URINALYSIS: by dipstick; full microscopic examination if dipstick positive; and
URINE DRUG SCREEN: ethyl alcohol, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates and phencyclidine
SERUM PREGNANCY SCREEN (female volunteers only)

If female and:

of childbearing potential, is practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as condom with spermicide, diaphragm, intrauterine device (IUD), or abstinence; or
is postmenopausal for at least 2 years; or
is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy)

Exclusion Criteria

Volunteers with a recent history of drug or alcohol addiction or abuse
Volunteers with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease (as determined by the clinical investigators)
Volunteers whose clinical laboratory test values are outside the accepted reference range and when confirmed on re-examination are deemed to be clinically significant
Volunteers demonstrating a positive hepatitis B surface antigen screen or a reactive HIV antibody screen
Volunteers demonstrating a positive drug screen when screened for this study
Female volunteers demonstrating a positive pregnancy screen
Female volunteers who are currently breastfeeding
Volunteers with a history of allergic response(s) to quinine or related drugs
Volunteers with a history of clinically significant allergies including drug allergies
Volunteers with a history of clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators)
Volunteers who currently use tobacco products
Volunteers who have taken any drug known to induce or inhibit hepatic drug metabolism in the 28 days prior to Period I dosing
Volunteers who report donating greater than 150mL of blood within 28 days prior to Period I dosing. All subjects will be advised not to donate blood for four weeks after completing the study
Volunteers who have donated plasma (e.g. plasmapheresis) within 14 days prior to Period I dosing. All subjects will be advised not to donate plasma for four weeks after completing the study
Volunteers who report receiving any investigational drug within 28 days prior to Period I dosing
Volunteers who report taking any systemic prescription medication in the 14 days prior to Period I dosing
Volunteers with QTc >480 msec on the screening electrocardiogram (ECG) or with clinically significant findings
Volunteers who have a glucose-6-phosphate dehydrogenese deficiency (G6PD)

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Quinine Sulfate Caps 324 mg - Fasting	Quinine Sulfate Capsules 324 mg	A single dose of quinine sulfate 324 mg administered with 240 mL of room temperature water after an overnight fast of at least 10 hours.
Quinine Sulphate Tabs 300 mg - Fasting	Quinine Sulphate Tablets 300 mg	A single dose of quinine sulphate 300 mg administered with 240 mL of room temperature water after an overnight fast of at least 10 hours.
Quinine Sulfate Caps 324 mg - Fed	Quinine Sulfate Capsules 324 mg	A single dose of quinine sulfate 324 mg administered with 240 mL of room temperature water thirty minutes after the initiation of a standardized, high-fat breakfast.

Primary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration (Cmax)	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.	The maximum or peak concentration that the drug reaches in the plasma.
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]	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.	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.
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]	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.	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.