A Dose Proportionality Study of Quinine Sulfate Capsules Under Fasting Conditions

• ClinicalTrials.gov Identifier: NCT00726895
• 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: May 2004
• Actual Primary Completion Date: June 2004 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 24, 2009)

• Maximum Plasma Concentration (Cmax) [ Time Frame: 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. ]
  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 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. ]
  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 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. ]
  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: two 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 Dose Proportionality Study of Quinine Sulfate Capsules Under Fasting Conditions
• Official Title: A Randomized, Two-way Crossover Design Used to Compare the Dose Proportionality of Quinine Sulfate Capsules, 324 mg Following a Single Oral Dose of 1 x 324 mg Capsule Versus 2 x 324 mg Capsules in Healthy Adult Volunteers
• Brief Summary: The purpose of this study is to evaluate and compare the dose proportionality of 324 mg Quinine Sulfate capsules following a single oral dose (1 x 324 mg capsules versus 2 x 324 mg capsules) in healthy adult volunteers when administered under fasting conditions.

Detailed Description

The purpose of this study is to evaluate and compare the dose proportionality of 324 mg Quinine Sulfate capsules following a single oral dose (1 x 324 mg capsules versus 2 x 324 mg capsules) in healthy adult volunteers when administered under fasting conditions.

Twenty-four healthy, non-smoking, non-obese, male and female volunteers at least 18 years of age will be randomly assigned in a crossover fashion to receive each of two Quinine Sulfate dosing regimens in sequence with a 7 day washout period between dosing periods. On the morning of Day 1, after an overnight fast of at least 10 hours, subjects will receive either a single oral dose of treatment A, Quinine Sulfate 1 x 324 mg capsule, or a single oral dose of treatment B, Quinine Sulfate 2 x 324 mg capsules. After a 7 day washout period,on the morning of Day 8 following an overnight fast of at least 10 hours, subjects will receive the alternate regimen. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of Quinine Sulfate. Blood sampling will then continue on a non-confined basis at 36 and 48 hours post-dose. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout the confinement portion of the study for adverse reactions to the study drug and/or procedures. Blood pressure and heart rate will be obtained prior to dosing and as scheduled following each dose. All adverse events whether elicited by query, spontaneously reported, or observed by clinic staff will be evaluated by the investigator and reported in the subject's case report form.

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

Intervention

• Drug: Quinine Sulfate Capsules 324 mg
  1 x 324 mg capsule
• Drug: Quinine Sulfate Capsules 324 mg
  2 x 324 mg capsules

Study Arms

• Experimental: Quinine Sulfate Capsules 1 x 324 mg Dose
  Quinine Sulfate 1 x 324 mg capsule dose.
  Intervention: Drug: Quinine Sulfate Capsules 324 mg
• Experimental: Quinine Sulfate Capsules 2 x 324 mg Dose
  Quinine Sulfate 2 x 324 mg capsules dose.
  Intervention: Drug: Quinine Sulfate Capsules 324 mg

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 31, 2008): 24
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: June 2004
• Actual Primary Completion Date: June 2004 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Screening Demographics: All volunteers will be healthy men or women 18 years of age or older at 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 screening evaluation and human immunodeficiency virus (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, but may not be limited to, an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems.
• The screening clinical laboratory procedures will include:
• HEMATOLOGY: hematocrit, hemoglobin, white blood cell (WBC) count with differential, red blood cell (RBC) count, platelet count;
• CLINICAL CHEMISTRY: serum creatinine, blood urea nitrogen (BUN), glucose, AST(SGOT - Serum glutamic-oxaloacetic transaminase), ALT(SGPT - Serum glutamic-pyruvic transaminase), 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 1 year; 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 abuse 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 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 150 mL 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 a QTc (corrected QT interval) > 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: Not Provided

Administrative Information

• NCT Number: NCT00726895
• Other Study ID Numbers: R04-0376
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Matthew W. Davis, MD,, Mutual Pharmaceutical
• Original Responsible Party: Same as current
• Current Study Sponsor: Mutual Pharmaceutical Company, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Mutual Pharmaceutical Company, Inc.
• Verification Date: January 2010