Drug - Drug Interaction Study of Quinine Sulfate and Ciprofloxacin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier:
NCT00785980
First received: November 3, 2008
Last updated: July 31, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Quinine Sulfate Capsules 324 mg
Drug: Ciprofloxacin 500 mg
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: 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

Resource links provided by NLM:


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

Primary Outcome 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. ] [ Designated as safety issue: No ]
    The maximum or peak concentration that the drug 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 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. ] [ Designated as safety issue: No ]
    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.

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


Enrollment: 24
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: Quinine Sulfate
Baseline quinine sulfate pharmacokinetics
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.
Other Name: Qualaquin®
Experimental: Quinine Sulfate with Ciprofloxacin
Quinine sulfate pharmacokinetics in the presence of steady state ciprofloxacin
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.
Other Name: Cipro®
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.
Other Name: Qualaquin®

Detailed Description:

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.

  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)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
  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: NCT00785980

Sponsors and Collaborators
Mutual Pharmaceutical Company, Inc.
Investigators
Principal Investigator: Anthony R Godfrey, PharmD PRACS Institute, Ltd.
  More Information

Additional Information:
No publications provided

Responsible Party: Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier: NCT00785980     History of Changes
Other Study ID Numbers: MPC-001-08-1027
Study First Received: November 3, 2008
Results First Received: September 10, 2009
Last Updated: July 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Mutual Pharmaceutical Company, Inc.:
quinine sulfate
ciprofloxacin
drug interactions
cytochrome p450
male
female
adult
pharmacokinetics

Additional relevant MeSH terms:
Ciprofloxacin
Quinine
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on September 18, 2014