Mefloquine Bioequivalence Among 3 Commercially Available Tablets.

Mefloquine Bioequivalence Among Three Commercial Tablet Formulations in Peruvian Subjects With Uncomplicated Plasmodium Falciparum Malaria

The objective of this study was to determine the bioequivalence among three commercial tablet formulations of MQ, i.e. Lariam, Mephaquin, and Mefloquine-(AC Farma) when given in combination with artesunate.

Study Overview

• Status: Completed
• Conditions: Malaria

Detailed Description

Pharmacokinetic parameters were determined for mefloquine in whole blood from Peruvian subjects with uncomplicated falciparum malaria administered Mephaquin®, Mefloquine-AC Farma, and Lariam®. The Mefloquine-AC Farma arm comprised 13 patients while the reference (Lariam) and Mephaquin arms consisted of 12 patients. Although Cmax was significantly less (p=0.04) in the Mephaquin arm (AUC0-t = 2500 ng/ml/day) relative to the reference (AUC0-t = 2820 ng/ml/day) arm, there were no significant differences in the AUC∞, tmax, and t1/2 for Mefloquine-AC Farma or Mephaquin relative to the reference. Except for the Cmax of the Mefloquine-AC Farma, the 90% confidence intervals for all parameters of both treatments were outside the specified FDA range of 80-125%. Therefore both formulations were not considered bioequivalent to the reference.

• Study Type: Observational
• Enrollment (Actual): 39

Contacts and Locations

Study Locations

• Peru
  • Iquitos, Peru
    • Apoyo Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Thirty-nine adult subjects were initially enrolled in the study ranging in age from 18-61 years with a mean of 36 years. Seventy-two percent of the volunteer patients were male.

Description

Inclusion Criteria:

• The inclusion criteria for enrolling patients included; male or non-pregnant female ≥ 18 years of age, infection with P. falciparum alone, with a parasite density between 250 and 50,000 asexual parasites/mm3 as determined by microscopic examination of a thick blood smear, informed consent from patient, and a willingness to be hospitalized for the first 24 hours after therapy is initiated and to return for follow-up visits through day 56.

Exclusion Criteria:

• Patients exhibiting evidence of severe malaria or with a history of an underlying chronic disease or illness that could interfere with the absorption of MQ, a history of hypersensitivity to MQ, or a history of neuropsychiatric illness or cardiac conduction problems were excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Reference; Lariam was administered as whole tablets with food and water at a dose of 25 mg/kg (15 mg/kg on the first day and 10mg/kg on the second day) along with artesunate at a dose of 4 mg/kg/day for three days under supervision by clinical staff
T1; Mephaquin was administered as whole tablets with food and water at a dose of 25 mg/kg (15 mg/kg on the first day and 10mg/kg on the second day) along with artesunate at a dose of 4 mg/kg/day for three days under supervision by clinical staff
T2; Mefloquine-AC Farma was administered as whole tablets with food and water at a dose of 25 mg/kg (15 mg/kg on the first day and 10mg/kg on the second day) along with artesunate at a dose of 4 mg/kg/day for three days under supervision by clinical staff

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Measure concentrations of mefloquine in blood to determine pharmacokinetic parameters and assess bioequivalence.	56 days

Collaborators and Investigators

• Sponsor: Centers for Disease Control and Prevention
• Collaborators: Universidad Peruana Cayetano Heredia; Naval Medical Research Center; Ministry of Health, Lima Peru
• Investigators: Principal Investigator: Michael D Green, PhD, Centers for Disease Control and Prevention; Principal Investigator: Wilmer Marquino, MD, Instituto Nacional de Salud, Lima, Peru; Principal Investigator: David Bacon, PhD, Naval Medical Research Center Detachment

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Study Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: October 12, 2007
• First Submitted That Met QC Criteria: October 12, 2007
• First Posted (Estimate): October 16, 2007

Study Record Updates

• Last Update Posted (Estimate): October 16, 2007
• Last Update Submitted That Met QC Criteria: October 12, 2007
• Last Verified: October 1, 2007

More Information

Terms related to this study

• Keywords: Mefloquine
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria
• Other Study ID Numbers: CDC-NCZVED-3620; DoD#31595