Comparative Study of Quinine Sulfate in Healthy Patients and in Patients With Renal Impairment - Full Text View

Sponsored by:	Mutual Pharmaceutical Company, Inc.
Information provided by:	Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier:	NCT00785551

Purpose

The effects of mild or moderate renal impairment (creatinine clearance 30 to 50 ml/min or >50 to 80 ml/min, respectively) on the pharmacokinetic profile of quinine and its active metabolite, 3'-hydroxyquinine, will be investigated. Safety and tolerability in healthy subjects versus those with mild to moderate renal impairment will be compared, as well.

Condition	Intervention	Phase
Healthy Renal Impairment	Drug: quinine sulfate	Phase I

Drug Information available for: Quinine Quinine bisulfate Quinine hydrochloride Quinine sulfate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Non-Randomized, Open Label, Parallel Assignment, Pharmacokinetics Study
Official Title:	A Single-Dose, Open-Label Comparative Study of the Pharmacokinetics, Safety,and Tolerability of Oral Quinine Sulfate in Healthy Volunteers and Adults With Mild and Moderate Renal Impairment

Further study details as provided by Mutual Pharmaceutical Company, Inc.:

Primary Outcome Measures:

Alterations pharmacokinetic profile of quinine and 3'-hydroxyquinine in plasma (total and free) and urine following a single 648mg dose of quinine sulfate in healthy subjects with normal renal function versus those with mild and moderate renal impairment [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Differences in safety and tolerability of quinine sulfate in healthy subjects versus those with mild and moderate renal impairment [ Time Frame: up to 72 hours ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	18
Study Start Date:	November 2007
Estimated Study Completion Date:	September 2009
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental quinine sulfate 648mg in subjects with normal renal function (CLcr > 80mL/min)	Drug: quinine sulfate 2 x 324mg given in one dose to healthy subjects
2: Experimental quinine sulfate 648mg in subjects with mildly impaired renal function (CLcr > 50 to 80 mL/min)	Drug: quinine sulfate 2 x 324mg given as one dose to subjects with mild renal impairment
3: Experimental quinine sulfate 648mg in subjects with moderately impaired renal function (CLcr 30 to 50mL/min)	Drug: quinine sulfate 2 x 324mg given as one dose to subjects with moderate renal impairment

Detailed Description:

Since many of the adverse events associated with quinine are dose-related, it is important to consider how varying degrees of renal dysfunction alter quinine pharmacokinetics possibly warranting dosage adjustment in these patients. This study will compare the pharmacokinetics of quinine in patients with normal, mild or moderate renal impairment. Eighteen non-smoking males and female volunteers between 18-65 years of age weighing at least 60 kg with BMI between 18- 40 kg/m2 will be divided into 3 groups of 6 subjects each based on renal function as defined (6 normal, 6 mild impairment, 6 moderate impairment). Subjects will be confined to the study unit during the entire 5 day study period beginning on the evening of Day -3. To confirm renal function classification, creatinine clearance will be measured via 24-hour urine collection from 7am Day -2 until 7am Day -1. On day 1, after a fast of at least 8 hours, each patient will receive a single 648 mg dose of quinine sulfate. Blood and urine samples will be collected at times sufficient to adequately define the pharmacokinetics of quinine and its active metabolite, 3'-hydroxyquinine) in the three study groups. Subjects will be monitored regarding adverse effects throughout study participation.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

All subjects - non-smoking, male and female volunteers 18-65 years of age weighing at least 60kg with BMI between 18- 40kg/m2. Females of childbearing potential sexually inactive or using acceptable birth control method for 14 days prior to through 3 days following dosing or postmenopausal with amenorrhea for at least 2 years, adequate venous access
Healthy subjects - medically healthy based on designated clinical criteria including CLcr>80 ml/min and hemoglobin 11g/dL or greater
Renally-impaired subjects - medically acceptable based on designated clinical criteria including good glucose control if diabetic, CLcr 30 to 80 ml/min, hemoglobin 10 g/dL or greater, anticipation that medications necessary for treatment of renal disease and/or other coexisting disease will remain stable for 14 days prior to and throughout the study period

Exclusion Criteria:

Pregnant or lactating; history of presence of significant cardiovascular, pulmonary, hepatic, hematologic, gastrointestinal, endocrine, immunologic, musculoskeletal, dermatologic, neurologic, or psychiatric disease; positive at screening for HIV, HbsAg, or HCV; QTc >440 msec (male) or 450 msec (female) or PR >200 msec, sitting BP < 90/55, sitting radial pulse < 45 bpm at screening or baseline; history of G6PD deficiency, myasthenia gravis, or optic neuritis; hypersensitivity or idiosyncratic reaction to mefloquine or quinidine; recent/ongoing use of drugs or substances known to inhibit or induce CYP P450 enzymes and/or P-glycoprotein or quinine; hx of alcoholism or drug abuse within previous 2 years; donation of blood or plasma within 56 days prior to dosing; receipt of study medication in another clinical trial within 30 days of dosing

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00785551

Locations

United States, Florida
Allied Research International - Cetero Research	Recruiting
Miami Gardens, Florida, United States, 33169
Contact: Gil Weiner, MD 305-624-9191
Principal Investigator: Gil Weiner, MD

Sponsors and Collaborators

Mutual Pharmaceutical Company, Inc.

Investigators

Study Chair:

Matthew Davis, M.D.

Mutual Pharmaceutical

More Information

Responsible Party:	Mutual Pharmaceutrical Company ( Vice President Branded Products and Medical Affairs )
Study ID Numbers:	MPC-001-07-1008
Study First Received:	November 3, 2008
Last Updated:	November 4, 2008
ClinicalTrials.gov Identifier:	NCT00785551
Health Authority:	United States: Food and Drug Administration

Keywords provided by Mutual Pharmaceutical Company, Inc.:

male
female
pharmacokinetics
normal and impaired renal function

Study placed in the following topic categories:

Quinine
Healthy

Additional relevant MeSH terms:

Anti-Infective Agents
Antiprotozoal Agents
Physiological Effects of Drugs
Neuromuscular Agents
Pharmacologic Actions
Antimalarials
Antiparasitic Agents

Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Muscle Relaxants, Central
Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009