Drug - Drug Interaction Study of Quinine Sulfate and Ciprofloxacin

Official Title: “A One-Directional, Open-Label Drug Interaction Study to Investigate the Effects of Multiple-Dose Ciprofloxacin HCl on the Single-Dose Pharmacokinetics of Quinine in Healthy Volunteers”

Ciprofloxacin is moderate inhibitor of cytochrome P450 1A2 (CYP1A2), one of the enzymes responsible for the metabolism of quinine. This study will evaluate the effect of ciprofloxacin-related inhibition of CYP1A2 on the pharmacokinetics of quinine sulfate.

Ciprofloxacin is moderate inhibitor of cytochrome P450 1A2 (CYP1A2), one of the enzymes responsible for the metabolism of quinine. This study will evaluate the effect of ciprofloxacin-related inhibition of CYP1A2 on the pharmacokinetics of quinine sulfate.

In the morning 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 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 36 hours post-dose at times sufficient to adequately define the pharmacokinetics of quinine sulfate. A 7-day washout period will be completed after the first dose of quinine sulfate on Day 1. Beginning at 07:45 am on Day 8 and continuing through Day 10, all subjects will return to the clinic for non-confined dosing of ciprofloxacin (1 x 500 mg tablet) every 12 hours. Administered ciprofloxacin doses on these days will not be in a fasted state. At 07:45 am on Day 11 after a fast of at least 10 hours, all study participants will receive a co-administered single oral dose of quinine sulfate (2 x 324 mg capsules) and ciprofloxacin (1 x 500 mg tablet). A final dose of ciprofloxacin (1 x 500 mg tablet) will be administered 12 hours later. Blood samples will be drawn from all participants before dosing and for 36 hours post-dose at times sufficient to adequately define the pharmacokinetics of quinine sulfate. Fasting will continue for 4 hours following the co-administered dose of quinine sulfate and ciprofloxacin. 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. Seated blood pressure and pulse will be measured pre-dose and at 1, 2 and 3 hours post-dose on Days 1 and 11. An electrocardiogram (ECG) will be done pre-dose and at 1, 2 and 4 hours post-dose on Days 1 and 11. 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.

Intervention(s) in this Clinical Trial

• Drug: Quinine Sulfate Capsules 324 mg
  • A single dose of quinine sulfate (2 x 324 mg capsules) administered on the morning of Day 1 after an overnight fast of at least 10 hours.
• Drug: Ciprofloxacin 500 mg
  • A single dose of quinine sulfate (2 x 324 mg capsules) co-administered with a single dose of ciprofloxacin (1 x 500 mg tablet) in the morning on Day 11 after an overnight fast of at least 10 hours.
• Drug: Quinine Sulfate Capsules 324 mg
  • A single dose of quinine sulfate (2 x 324 mg capsules) co-administered with a single dose of ciprofloxacin (1 x 500 mg tablet) in the morning on Day 11 after an overnight fast of at least 10 hours.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Quinine Sulfate
  • Baseline quinine sulfate pharmacokinetics
• Experimental: Quinine Sulfate with Ciprofloxacin
  • Quinine sulfate pharmacokinetics in the presence of steady state ciprofloxacin

Primary Measures

• Maximum Plasma Concentration(Cmax)
  • Time Frame: Serial pharmacokinetic blood samples for quinine sulfate collected on Days 1 and 11 before dosing and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 and 36 hours post-dose.
    Safety Issue?: No
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
  • Time Frame: Serial pharmacokinetic blood samples for quinine sulfate collected on Days 1 and 11 before dosing and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 and 36 hours post-dose.
    Safety Issue?: No
• Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)].
  • Time Frame: Serial pharmacokinetic blood samples for quinine sulfate collected on Days 1 and 11 before dosing and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 and 36 hours post-dose.
    Safety Issue?: No

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)between 18 and 32
• Medically healthy on the basis of medical history and physical examination
• Hemoglobin > or = to 11.5 g/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 mefloquine or quinidine

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Mutual Pharmaceutical Company, Inc. Industry

Overall Clinical Trial Officials and Contacts

Anthony R Godfrey, PharmD Principal Investigator PRACS Institute, Ltd.  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00785980

Study ID Number: MPC-001-08-1027

ClinicalTrials.gov Identifier: NCT00785980

Health Authority: United States: Food and Drug Administration

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