Drug-Drug Interaction Study Between Quinine Sulfate and Rosiglitazone

NCT ID: NCT00785213

Last Updated: 2012-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2008-10-31

Brief Summary

Rosiglitazone is predominantly metabolized by cytochrome P450 (CYP) 2C8. Quinine sulfate is an inhibitor of CYP 2C8. This study will evaluate the effect of multiple doses of quinine sulfate at steady-state on the pharmacokinetics of single-dose rosiglitazone in healthy adult subjects.

Detailed Description

Rosiglitazone is predominantly metabolized by cytochrome P450 (CYP) 2C8. Quinine sulfate is an inhibitor of CYP 2C8. This study will evaluate the effect of multiple doses of quinine sulfate at steady-state on the pharmacokinetics of single-dose rosiglitazone in healthy adult subjects.

On study Day 1 after a fast of at least 10 hours, twenty four healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 will be given one oral dose of rosiglitazone (1 x 4 mg tablet). Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose at times sufficient to adequately define the pharmacokinetics of rosiglitazone. A 2 day washout period will be completed after the first dose of rosiglitazone on Day 1. On Days 4-7 all subjects will receive a dose of quinine sulfate (2 x 324 mg capsules) every 8 hours starting with the 7:15 a.m. dose on Day 4 and continuing through the 11:15 p.m. dose on Day 7. Doses of quinine sulfate on Days 4-6 will be administered without regard to meals. On the morning of Day 7 after an overnight fast of at least 10 hours, all study participants will receive co-administered doses of rosiglitazone (1 x 4 mg tablet) and quinine sulfate (2 x 324 mg capsules). Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose at times sufficient to adequately determine the pharmacokinetics of rosiglitazone. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Blood pressure (sitting for at least 3 minutes) and pulse will be measured prior to dosing and at 1, 2 and 3 hours after the morning dose of rosiglitazone on Days 1 and 7. Electrocardiograms (EKG) will be recorded on Day 4 before dosing of quinine sulfate and at 1, 2 and 4 hours post-dose and on Day 7 before the co-administered doses of rosiglitazone and quinine sulfate and at 1, 2 and 4 hours post-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.

Conditions

Healthy

Keywords

rosiglitazone; quinine sulfate; drug interactions; cytochrome p450

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Rosiglitazone Alone

Baseline rosiglitazone pharmacokinetics.

Group Type: ACTIVE_COMPARATOR

Rosiglitazone 4 mg Tablets

Intervention Type: DRUG

Rosiglitazone 4 mg tablet administered as a single oral dose on the morning of Day 1.

Rosiglitazone with Steady State Quinine Sulfate

Rosiglitazone pharmacokinetics in the presence of steady state quinine sulfate.

Group Type: EXPERIMENTAL

Rosiglitazone 4 mg Tablets

Intervention Type: DRUG

Co-administered single oral doses of rosiglitazone 4 mg (1 x 4 mg tablet) and quinine sulfate 648 mg (2 x 324 mg capsules) on the morning of Day 7.

Quinine Sulfate 324 mg Capsules

Intervention Type: DRUG

Co-administered single oral doses of rosiglitazone 4 mg (1 x 4 mg tablet) and quinine sulfate 648 mg (2 x 324 mg capsules) on the morning of Day 7.

Interventions

Rosiglitazone 4 mg Tablets

Rosiglitazone 4 mg tablet administered as a single oral dose on the morning of Day 1.

Intervention Type: DRUG

Rosiglitazone 4 mg Tablets

Co-administered single oral doses of rosiglitazone 4 mg (1 x 4 mg tablet) and quinine sulfate 648 mg (2 x 324 mg capsules) on the morning of Day 7.

Intervention Type: DRUG

Quinine Sulfate 324 mg Capsules

Co-administered single oral doses of rosiglitazone 4 mg (1 x 4 mg tablet) and quinine sulfate 648 mg (2 x 324 mg capsules) on the morning of Day 7.

Intervention Type: DRUG

Other Intervention Names

Avandia®; Avandia®; Qualaquin®

Eligibility Criteria

Inclusion Criteria

• Healthy adults 18-45 years of age
• Non-smoking
• Non-pregnant (post-menopausal, surgically sterile or using effective contraceptive measures)
• Body mass index (BMI) less than or equal to 32
• Medically healthy on the basis of medical history and physical examination
• Hemoglobin > or = to 11.5g/dL
• Completion of the screening process within 28 days prior to dosing
• Provision of voluntary written informed consent

Exclusion Criteria

• Recent participation (within 28 days) in other research studies
• Recent significant blood donation or plasma donation
• Pregnant or lactating
• Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV)
• Recent (2-year) history or evidence of alcoholism or drug abuse
• History or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
• Subjects who have used any drugs or substances known to inhibit or induce cytochrome (CYP) P450 enzymes and/or P-glycoprotein (P-gp) within 28 days prior to the first dose and throughout the study
• Drug allergies to quinine sulfate or rosiglitazone

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cetero Research, San Antonio

NETWORK

Sponsor Role: collaborator

Mutual Pharmaceutical Company, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew Davis, MD

Role: STUDY_CHAIR

Mutual Pharmaceutical Company, Inc.

Locations

Cetero Research

East Grand Forks, Minnesota, United States

Countries

United States

Related Links

http://www.fda.gov/opacom/7alerts.html

Recalls, Market Withdrawals and Safety Alerts

http://dailymed.nlm.nih.gov/dailymed/about.cfm

Daily Med - Posting of Recently Submitted Labeling to the FDA

Other Identifiers

R08-0591

Identifier Type: -

Identifier Source: secondary_id

MPC-001-08-1028

Identifier Type: -

Identifier Source: org_study_id