Drug-Drug Interaction Study of Qualaquin and Midazolam - Full Text View

Sponsored by:	Mutual Pharmaceutical Company, Inc.
Information provided by:	Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier:	NCT00785486

Purpose

This is an open label non-randomized two way drug interaction study in healthy adult volunteers to determine the extent to which quinine, an inducer of cytochrome p450 CYP 3A4, affects the pharmacokinetics of midazolam, an accepted probe drug for CYP 3A4. The study will also determine the extent to which midazolam affects the pharmacokinetics of quinine.

Condition	Intervention	Phase
Healthy	Drug: midazolam and quinine Drug: quinine sulfate 324mg and midazolam 2mg	Phase I

Drug Information available for: Midazolam Midazolam hydrochloride Midazolam maleate Quinine Quinine bisulfate Quinine hydrochloride Quinine sulfate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Non-Randomized, Open Label, Single Group Assignment, Pharmacokinetics Study
Official Title:	A Pharmacokinetic Interaction Study Evaluating the Effect of Qualaquin (Quinine Sulfate) Capsules on Midazolam

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

Primary Outcome Measures:

90% confidence interval of ratios of least-squares means for the Ln transformed kinetic parameters of midazolam and its 1-hydroxy metabolite before and after quinine at steady state, and quinine at steady state before and after midazolam [ Time Frame: days 1 and 10 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

For informational purposes: 1 hydroxy-midazolam /midazolam ratios for AUC, Cmax and Tmax,;the least squares means for relevant PK parameters for quinine for day 4 (initial dose) vs. day 9 (steady state) will also be presented [ Time Frame: Days 1, 4, 9 and 10 ] [ Designated as safety issue: No ]

Enrollment:	24
Study Start Date:	March 2007
Study Completion Date:	March 2007
Primary Completion Date:	March 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1 baseline midazolam and metabolite pharmacokinetics and baseline quinine pharmacokinetics	Drug: midazolam and quinine midazolam 2mg and quinine 324mg
2: Experimental pharmacokinetics of quinine and midazolam in each other's presence	Drug: quinine sulfate 324mg and midazolam 2mg quinine 324mg and midazolam 2mg

Detailed Description:

This is an open label non-randomized two way drug interaction crossover study in healthy adult volunteers to determine the extent to which quinine, an inducer of cytochrome p450 CYP 3A4, affects the pharmacokinetics of midazolam, an accepted probe drug for CYP 3A4. The study will also determine the extent to which midazolam affects the pharmacokinetics of quinine. This will compare the pharmacokinetics of midazolam and quinine at baseline to their kinetics when they are taken together in 24 normal healthy adult volunteers who will serve as their own controls. All patients will be confined to the study site throughout the entire 11 day study period. On day 1 after a fast of at least 10 hours, all study participants will receive a single oral dose of midazolam 2mg. Blood will be drawn at times sufficient to adequately define the baseline concentration time curve for midazolam and its metabolite, 1-hydroxy-midazolam. On the morning of day 4, after a 3 day washout period and following a fast of at lease 10 hours, all volunteers will begin a regimen of 324 mg of quinine sulfate by mouth every 8 hours. All subjects will continue this regimen from day 4-10 (21 total doses). Blood will be drawn after the first daily dose of quinine on days 4 and 9 at times sufficient to adequately define the baseline and steady state concentration time curves for quinine. Additional blood will be drawn prior to the first daily dose of quinine on days 7,8,9,and 10. On day 10 after at least a 10 hour fast, all participants will receive both midazolam and quinine together. Blood will be drawn a times sufficient to characterize the pharmacokinetics of midazolam, 1-hydroxymidazolam and quinine under the stated conditions.

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Medically healthy non-smoking, non-obese (≥ 60kg males, ≥52kg females within 15% of IBW) adult volunteers 18-45 years of age

Exclusion Criteria:

Subjects with history or presence of significant cardiovascular disease (including hypotension, hypertension, bradycardia or EKG abnormalities), pulmonary, hepatic, gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychiatric disease or an active sexually transmitted disease.
Subjects with significant blood loss in the prior 56 days, plasma donation within 7 days , hemoglobin <12.0 g/dl or who have participated in another clinical trial within the prior 30 days.
Subjects with recent (2-year) history or evidence of alcoholism or drug abuse.
Subjects who have used any drugs or substances known to inhibit or induce cytochrome P450 (CYP) enzymes 10 days or 28 days respectively prior to the first dose and throughout the study.
Subjects who have received monoamine oxidase inhibitors or been on a special diet within 28 days of starting the study.
Subjects who test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV).

Subjects who are pregnant or lactating , taking hormone replacement therapy or have known allergies to quinine sulfate, mefloquine, quinidine or midazolam and other benzodiazepines.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00785486

Locations

United States, Arizona
MDS Pharma Services
Phoenix, Arizona, United States, 85044

Sponsors and Collaborators

Mutual Pharmaceutical Company, Inc.

Investigators

Study Chair:	Matthew Davis, MD	Mutual Pharmaceutical
Principal Investigator:	Dennis Swearingen, MD	MDS Pharma Services

More Information

Responsible Party:	Mutual Pharmaceutical Company, Inc. ( Vice President Branded Products and Medical Affairs )
Study ID Numbers:	MPC-001-07-1001
Study First Received:	November 4, 2008
Last Updated:	November 4, 2008
ClinicalTrials.gov Identifier:	NCT00785486
Health Authority:	United States: Food and Drug Administration

Keywords provided by Mutual Pharmaceutical Company, Inc.:

midazolam
drug interactions
cytochrome p450

Study placed in the following topic categories:

Quinine
Healthy
Midazolam

Additional relevant MeSH terms:

Anti-Infective Agents
Neurotransmitter Agents
Antiprotozoal Agents
Molecular Mechanisms of Pharmacological Action
GABA Modulators
Physiological Effects of Drugs
Psychotropic Drugs
Anesthetics
Neuromuscular Agents
Antimalarials
Antiparasitic Agents
Sensory System Agents
Therapeutic Uses
Muscle Relaxants, Central

Hypnotics and Sedatives
Analgesics
Anesthetics, Intravenous
Tranquilizing Agents
Central Nervous System Depressants
Pharmacologic Actions
Adjuvants, Anesthesia
Anesthetics, General
Analgesics, Non-Narcotic
GABA Agents
Anti-Anxiety Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009