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

• ClinicalTrials.gov Identifier: NCT00727272
• Recruitment Status: Completed
• First Posted: August 1, 2008
• Results First Posted: December 30, 2009
• Last Update Posted: January 20, 2010
• Sponsor: Mutual Pharmaceutical Company, Inc.
• Information provided by: Mutual Pharmaceutical Company, Inc.

Tracking Information

• First Submitted Date: July 30, 2008
• First Posted Date: August 1, 2008
• Results First Submitted Date: November 24, 2009
• Results First Posted Date: December 30, 2009
• Last Update Posted Date: January 20, 2010
• Study Start Date: February 2004
• Actual Primary Completion Date: March 2004 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 11, 2010)

• 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. ]
  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)] [ 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. ]
  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-∞)] [ 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. ]
  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.

• Original Primary Outcome Measures (submitted: July 31, 2008): Bioavailability [ Time Frame: 2 weeks ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Relative Bioavailability Study of Quinine Sulfate Capsules Under Fasting and Fed Conditions
• Official Title: A Relative Bioavailability Study of Quinine Sulfate Capsules Under Fasting and Fed Conditions
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Basic Science
• Condition: Healthy

Intervention

• Drug: Quinine Sulfate Capsules 324 mg
  One 324 mg capsule administered after an overnight fast of at least 10 hours.
• Drug: Quinine Sulphate Tablets 300 mg
  One 300 mg tablet administered after an overnight fast of at least 10 hours.
• Drug: Quinine Sulfate Capsules 324 mg
  One 324 mg capsule administered thirty minutes after the initiation of a standardized, high-fat breakfast.

Study Arms

• Experimental: Quinine Sulfate Caps 324 mg - Fasting
  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.
  Intervention: Drug: Quinine Sulfate Capsules 324 mg
• Experimental: Quinine Sulphate Tabs 300 mg - Fasting
  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.
  Intervention: Drug: Quinine Sulphate Tablets 300 mg
• Experimental: Quinine Sulfate Caps 324 mg - Fed
  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.
  Intervention: Drug: Quinine Sulfate Capsules 324 mg

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 31, 2008): 27
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: March 2004
• Actual Primary Completion Date: March 2004 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00727272
• Other Study ID Numbers: RA3-085
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Matthew Davis, MD, Mutual Pharmaceutical Company, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Mutual Pharmaceutical Company, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: James D Carlson, Pharm.D.; PRACS

• PRS Account: Mutual Pharmaceutical Company, Inc.
• Verification Date: January 2010