Clinical trial NCT00785213: Drug-Drug Interaction Study Between Quinine Sulfate and Rosiglitazone
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: rosiglitazone
quinine sulfate
drug interactions
cytochrome p450
Lead sponsor: Mutual Pharmaceutical Company, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cetero Research, San Antonio
First posted: 2008-11-05
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Rosiglitazone
timeFrame: serial pharmacokinetic blood samples drawn prior to dosing on Days 1 and 7 and then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 20 and 24 hours after dose administration.
measure: Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
timeFrame: serial pharmacokinetic blood samples drawn prior to dosing on Days 1 and 7 and then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 20 and 24 hours after dose administration.
measure: Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
timeFrame: serial pharmacokinetic blood samples drawn prior to dosing on Days 1 and 7 and then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 20 and 24 hours after dose administration.
Secondary outcomes:
Other outcomes:
Locations:
city: East Grand Forks
country: United States
facility: Cetero Research
state: Minnesota
Study officials:
affiliation: Mutual Pharmaceutical Company, Inc.
name: Matthew Davis, MD
role: STUDY_CHAIR
References: