Drug-Drug Interaction Study Between Quinine Sulfate and Rosiglitazone

This study has been completed.
Sponsor:
Collaborator:
Cetero Research, San Antonio
Information provided by (Responsible Party):
Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier:
NCT00785213
First received: October 24, 2008
Last updated: July 31, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Rosiglitazone 4 mg Tablets
Drug: Quinine Sulfate 324 mg Capsules
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Plasma Concentration (Cmax) of Rosiglitazone [ Time Frame: 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. ] [ Designated as safety issue: No ]
    The maximum or peak concentration that rosiglitazone reaches in the plasma.

  • Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] [ Time Frame: 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. ] [ Designated as safety issue: No ]
    The area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration (t), as calculated by the linear trapezoidal rule for rosiglitazone.

  • Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] [ Time Frame: 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. ] [ Designated as safety issue: No ]
    The area under the plasma concentration versus time curve from time 0 to infinity. [AUC(0-∞)] was calculated as the sum of AUC(0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant for rosiglitazone.


Enrollment: 23
Study Start Date: September 2008
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rosiglitazone Alone
Baseline rosiglitazone pharmacokinetics.
Drug: Rosiglitazone 4 mg Tablets
Rosiglitazone 4 mg tablet administered as a single oral dose on the morning of Day 1.
Other Name: Avandia®
Experimental: Rosiglitazone with Steady State Quinine Sulfate
Rosiglitazone pharmacokinetics in the presence of steady state quinine sulfate.
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.
Other Name: Avandia®
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.
Other Name: Qualaquin®

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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00785213

Locations
United States, Minnesota
Cetero Research
East Grand Forks, Minnesota, United States, 56721
Sponsors and Collaborators
Mutual Pharmaceutical Company, Inc.
Cetero Research, San Antonio
Investigators
Study Chair: Matthew Davis, MD Mutual Pharmaceutical Company, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier: NCT00785213     History of Changes
Other Study ID Numbers: MPC-001-08-1028, R08-0591
Study First Received: October 24, 2008
Results First Received: October 20, 2009
Last Updated: July 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Mutual Pharmaceutical Company, Inc.:
rosiglitazone
quinine sulfate
drug interactions
cytochrome p450

Additional relevant MeSH terms:
Quinine
Rosiglitazone
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Hypoglycemic Agents

ClinicalTrials.gov processed this record on August 19, 2014