Drug-Drug Interaction Study Between Quinine Sulfate and Rosiglitazone
Information source: Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: Rosiglitazone 4 mg Tablets (Drug); Rosiglitazone 4 mg Tablets (Drug); Quinine Sulfate 324 mg Capsules (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Mutual Pharmaceutical Company, Inc. Official(s) and/or principal investigator(s): Matthew Davis, MD, Study Chair, Affiliation: Mutual Pharmaceutical Company, Inc.
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.
Clinical Details
Official title: An Open-Label Drug-Drug Interaction Study to Investigate the Effects of Steady State Quinine on the Single-Dose Pharmacokinetics of Rosiglitazone Maleate in Healthy Volunteers
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: Maximum Plasma Concentration (Cmax) of RosiglitazoneArea Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Both.
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
Locations and Contacts
Cetero Research, East Grand Forks, Minnesota 56721, United States
Additional Information
Recalls, Market Withdrawals and Safety Alerts Daily Med - Posting of Recently Submitted Labeling to the FDA
Starting date: September 2008
Last updated: July 31, 2012
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