Drug-Drug Interaction Study Between Quinine Sulfate and Rosiglitazone

NCT00785213 | Completed Phase 1 Results

• 2 other identifiers: MPC-001-08-1028R08-0591
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

rosiglitazone; quinine sulfate; drug interactions; cytochrome p450

Outcome Measures

Primary Outcomes (3)

• Maximum Plasma Concentration (Cmax) of Rosiglitazone

  The maximum or peak concentration that rosiglitazone reaches in the plasma.

  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.

• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]

  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.

  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.

• Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]

  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.

  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.

Study Arms (2)

Rosiglitazone Alone

ACTIVE COMPARATOR

Baseline rosiglitazone pharmacokinetics.

Drug: Rosiglitazone 4 mg Tablets

Rosiglitazone with Steady State Quinine Sulfate

EXPERIMENTAL

Rosiglitazone pharmacokinetics in the presence of steady state quinine sulfate.

Drug: Rosiglitazone 4 mg Tablets; Drug: Quinine Sulfate 324 mg Capsules

Interventions

Rosiglitazone 4 mg Tablets DRUG

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

Also known as: Avandia®

Rosiglitazone Alone

Quinine Sulfate 324 mg Capsules 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.

Also known as: Qualaquin®

Rosiglitazone with Steady State Quinine Sulfate

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mutual Pharmaceutical Company, Inc.: lead
• Cetero Research, San Antonio: collaborator

Study Sites (1)

Cetero Research

East Grand Forks, Minnesota, 56721, United States

Location

Related Links

• Recalls, Market Withdrawals and Safety Alerts
• Daily Med - Posting of Recently Submitted Labeling to the FDA

MeSH Terms

Interventions

Rosiglitazone; Quinine

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cinchona Alkaloids; Alkaloids; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Medical Director
• Organization: Mutual Pharmaceutical Company, Inc.

clinicaltrials@urlmutual.com

215-697-1743

Study Officials

• Matthew Davis, MD

  Mutual Pharmaceutical Company, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2008
• First Posted: November 5, 2008
• Study Start: September 1, 2008
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: August 7, 2012
• Results First Posted: November 26, 2009

Record last verified: 2012-07

Locations

US (1)