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Comparative Study of Quinine Sulfate in Healthy Patients and in Patients With Renal Impairment

Primary Purpose

Healthy, Renal Impairment

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

quinine sulfate

About this trial

This is an interventional basic science trial for Healthy focused on measuring male, female, pharmacokinetics, normal and impaired renal function

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Cetero Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Arm Description

quinine sulfate 648mg in subjects with normal renal function (CLcr > 80mL/min)

quinine sulfate 648mg in subjects with mildly impaired renal function (CLcr > 50 to 80 mL/min)

quinine sulfate 648mg in subjects with moderately impaired renal function (CLcr 30 to 50mL/min)

Outcomes

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

Secondary Outcome Measures

Differences in safety and tolerability of quinine sulfate in healthy subjects versus those with mild and moderate renal impairment

Full Information

NCT ID

NCT00785551

First Posted

November 3, 2008

Last Updated

July 31, 2012

Sponsor

Mutual Pharmaceutical Company, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00785551

Brief Title

Comparative Study of Quinine Sulfate in Healthy Patients and in Patients With Renal Impairment

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2012

Overall Recruitment Status

Terminated

Why Stopped

poor enrollment

Study Start Date

November 2007 (undefined)

Primary Completion Date

January 2011 (Actual)

Study Completion Date

January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mutual Pharmaceutical Company, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Healthy, Renal Impairment

Keywords

male, female, pharmacokinetics, normal and impaired renal function

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

quinine sulfate 648mg in subjects with normal renal function (CLcr > 80mL/min)

Arm Title

Arm Type

Experimental

Arm Description

quinine sulfate 648mg in subjects with mildly impaired renal function (CLcr > 50 to 80 mL/min)

Arm Title

Arm Type

Experimental

Arm Description

quinine sulfate 648mg in subjects with moderately impaired renal function (CLcr 30 to 50mL/min)

Intervention Type

Drug

Intervention Name(s)

quinine sulfate

Other Intervention Name(s)

Qualaquin

Intervention Description

2 x 324mg given in one dose to healthy subjects

Intervention Type

Drug

Intervention Name(s)

quinine sulfate

Other Intervention Name(s)

Qualaquin

Intervention Description

2 x 324mg given as one dose to subjects with mild renal impairment

Intervention Type

Drug

Intervention Name(s)

quinine sulfate

Other Intervention Name(s)

Qualaquin

Intervention Description

2 x 324mg given as one dose to subjects with moderate renal impairment

Primary Outcome Measure Information:

Title

Time Frame

72 hours

Secondary Outcome Measure Information:

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Matthew Davis, M.D.

Organizational Affiliation

Mutual Pharmaceutical

Official's Role

Study Chair

Facility Information:

Facility Name

Cetero Research

City

Miami Gardens

State/Province

Florida

ZIP/Postal Code

33169

Country

United States

12. IPD Sharing Statement

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Comparative Study of Quinine Sulfate in Healthy Patients and in Patients With Renal Impairment

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