Drug - Drug Interaction Study Between Quinine Sulfate and Theophylline

NCT00779259 | Completed Phase 1 Results

• 2 other identifiers: MPC-001-07-1002R07-0738
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

In a prior in vitro study using human hepatocytes quinine was shown to induce the activity of Cytochrome p450 CYP 1A2. The present study will evaluate the extent to which quinine sulfate-related induction of this enzyme effects the pharmacokinetics of theophylline, a sensitive probe drug for the activity of CYP 1A2. It will also evaluate the effect of single-dose theophylline on the pharmacokinetics of steady-state quinine sulfate.

Conditions

Pharmacokinetics

Keywords

quinine sulfate; theophylline; drug interactions; cytochrome p450; humans; male; adult

Outcome Measures

Primary Outcomes (3)

• Maximum Plasma Concentration(Cmax)

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

  Serial pharmacokinetic blood samples for theophylline collected on Days 1 and 12 before dosing and for 48 hours post-dose. Serial pharmacokinetic blood samples for quinine collected on Days 11 and 12 before dosing and for 8 hours after the morning dose.

• 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 beginning from the first dose (time 0) to the last measurable concentration (time t), as calculated by the linear trapezoidal method.

  Serial pharmacokinetic blood samples for theophylline collected on Days 1 and 12 before dosing and for 48 hours post-dose. Serial pharmacokinetic blood samples for quinine collected on Days 11 and 12 before dosing and for 8 hours after the morning dose.

• Area Under the Concentration 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 the AUC(0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant.

  Serial pharmacokinetic blood samples for theophylline collected on Days 1 and 12 before dosing and for 48 hours post-dose.

Secondary Outcomes (2)

• Electrocardiogram (ECG) Evaluation of the Maximum QT Interval Corrected for Heartrate (QTc), Quinine Study Day 11.

  5 hours - measured 1 hour pre-dose and then at 4 hours after the morning dose on Day 11

• Electrocardiogram (ECG) Evaluation of the Maximum QT Interval Corrected for Heartrate (QTc), Theophylline Co-administered With Quinine, Study Day 12.

  5 hours - measured 1 hour pre-dose and then at 4 hours post-dose on Day 12

Study Arms (3)

Theophylline alone

ACTIVE COMPARATOR

baseline theophylline pharmacokinetics

Drug: Theophylline 300mg

Quinine alone

ACTIVE COMPARATOR

baseline quinine pharmacokinetics at steady state

Drug: Quinine 648 mg

Theophylline with steady state quinine

EXPERIMENTAL

Theophylline pharmacokinetics in the presence of steady state quinine and quinine pharmacokinetics in the presence of theophylline.

Drug: Theophylline 300 mg; Drug: Quinine 648 mg

Interventions

Theophylline 300mg DRUG

Single doses of theophylline 300 mg as an immediate-release oral solution 80mg/15ml concentration administered alone at 7 am on Day 1 after an overnight fast of at least 10 hours and along with quinine sulfate (2 x 324 mg capsules) at 7am on Day 12 after an overnight fast of at least 10 hours.

Theophylline alone

Quinine 648 mg DRUG

648 mg quinine sulfate(2 x 324 mg capsules) initiated at 3pm on Day 5 and taken every 8 hours through Day 11 and co-administered with theophylline 300 mg as an immediate-release oral solution 80 mg/15 ml concentration at 7am on Day 12.

Quinine alone

Theophylline 300 mg DRUG

Single doses of theophylline 300 mg as an immediate-release oral solution 80mg/15ml concentration administered alone at 7 am on Day 1 after an overnight fast of at least 10 hours and along with quinine sulfate (2 x 324 mg capsules) at 7am on Day 12 after an overnight fast of at least 10 hours.

Theophylline with steady state quinine

Eligibility Criteria

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

You may qualify if:

• Medically healthy non-smoking, non-obese (≥ 55kg and within 15% of ideal body weight) adult male volunteers 18-45 years of age

You may not qualify if:

• Subjects with history or presence of glucose 6 phosphate dehydrogenase deficiency, myasthenia gravis, optic neuritis, glaucoma or significant cardiovascular disease (including hypotension, 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 and/or P-glycoprotein within 30 days prior to the first dose and throughout 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 or have hypersensitivity to quinine sulfate, mefloquine, quinidine or hypersensitivity to theophylline or aminophylline.

Sponsors & Collaborators

• Mutual Pharmaceutical Company, Inc.: lead

Study Sites (1)

PRACS Institute

Fargo, North Dakota, 58104, United States

Location

MeSH Terms

Interventions

Theophylline; Quinine

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cinchona Alkaloids; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Quinolines

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

  STUDY CHAIR

• Barrie March, MD

  PRACS Institute

  PRINCIPAL INVESTIGATOR

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

Study Record Dates

• First Submitted: October 22, 2008
• First Posted: October 24, 2008
• Study Start: August 1, 2007
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: October 28, 2009
• Results First Posted: July 17, 2009

Record last verified: 2009-10

Locations

US (1)