Safety, Tolerability & Pharmacokinetics (PK) of Co-administered Single Doses of OZ439 and Mefloquine (MQ) in Healthy Volunteers

A Phase I Healthy Volunteer Study Investigating the Safety, Tolerability & Pharmacokinetics of Co-administered Single Doses of OZ439 and Mefloquine

OZ439 is a novel, synthetic trioxolane medicine which is related to artemisinin, but has the advantage of a longer elimination half-life so is being developed to be administered together with a potential partner drug e.g. mefloquine as a single dose cure for uncomplicated malaria. The study findings will be used to inform the dose and design of future studies. The aim of the study is to establish the safety, tolerability and pharmacokinetics of co-administered OZ439 and MQ at a range of doses up to the maximum tolerated dose, in healthy volunteers.

Study Overview

• Status: Terminated
• Conditions: Malaria
• Intervention / Treatment: Drug: Placebo; Drug: OZ439 100mg; Drug: MQ 250 mg, single dose; Drug: OZ439 400mg; Drug: MQ 750mg, single dose

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Cape Town, South Africa, 7925
    • Division of Clinical Pharmacology, University of Cape Town

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and non-childbearing potential female volunteers of between 18 and 55 years of age
• Female volunteers must have a negative serum pregnancy test at screening
• Females must be of non-childbearing potential
• Male volunteers and their partner(s) must agree to use a double barrier method of contraception for at least 14 days prior to first dose of study drug through 90 days after the last dose.
• Body mass Index between 18 and 30kg/m2, inclusive; and a total body weight >50 kg
• Laboratory tests at screening within normal ranges or not clinically significant as judged by the Investigator.

Exclusion Criteria:

• Received an investigational drug or participated in another research study within 30 days of the first dose of study drug or at any time through the study
• Evidence of current or history of clinically significant oncologic, pulmonary, hepatic, cardiovascular, gastrointestinal, haematologic, metabolic, neurological, immunologic, nephrologic, endocrine, psychiatric disease, or clinically significant current infection.
• Any condition that could possibly affect drug absorption, such as gastrectomy, diarrhea and lactose intolerance
• Use of any medications, vitamins, herbal supplements, dietary supplements or vaccinations within 14 days of the first dose of study drug or at any time through the study, unless prior approval is granted. This includes any drugs that are substrates, inhibitors or inducers of CYP3A4. Intermittent use of acetaminophen at doses of up to 2g/day is permitted
• History of drug or alcohol abuse within 2 years of Screening
• History of alcohol consumption within 24 hours of any study visit
• Tobacco users
• Consumption of fruit juices within 7 days prior to dosing
• Participation in unaccustomed strenuous exercise within 7 days prior to
• Positive urine drug screen
• Positive test for HIV-1, HBsAg or HCV
• Known hypersensitivity to MQ or artemisinins
• QTcF greater than 450msec

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: OZ439 100mg single dose; OZ439 100mg single dose oral suspension	Drug: OZ439 100mg; OZ439 100mg oral suspension, single dose
Experimental: OZ439 100mg plus MQ 250mg single doses; Single dose OZ439 100mg oral suspension in combination with single dose MQ 250mg tablet	Drug: OZ439 100mg; OZ439 100mg oral suspension, single dose; Drug: MQ 250 mg, single dose; Mefloquine 250 mg tablet, single dose
Experimental: OZ439 400mg single dose; OZ439 400mg single dose oral suspension	Drug: OZ439 400mg; OZ439 400mg oral suspension, single dose
Experimental: OZ439 400mg plus MQ 750mg single doses; Single dose OZ439 400mg oral suspension in combination with single dose MQ 750mg tablets	Drug: OZ439 400mg; OZ439 400mg oral suspension, single dose; Drug: MQ 750mg, single dose; Mefloquine 750mg oral tablet, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OZ439 AUC0-t	Area under the plasma concentration versus time curve (AUC) of OZ439	Up to 42 days post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OZ439 Cmax	Peak Plasma Concentration (Cmax) of OZ439	Up to 42 days post-dose
MQ AUC0-t	Area under the plasma concentration versus time curve (AUC) of MQ	Up to 42 days post-dose
MQ Cmax	Peak Plasma Concentration (Cmax) of MQ	Up to 42 days post-dose

Collaborators and Investigators

• Sponsor: Medicines for Malaria Venture
• Collaborators: University of Cape Town
• Investigators: Principal Investigator: Karen I Barnes, University of Cape Town

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: June 7, 2012
• First Submitted That Met QC Criteria: June 8, 2012
• First Posted (Estimate): June 11, 2012

Study Record Updates

• Last Update Posted (Estimate): April 16, 2015
• Last Update Submitted That Met QC Criteria: March 27, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Malaria; PK; Healthy Volunteers; Mefloquine; OZ439
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Artefenomel
• Other Study ID Numbers: MMV_OZ439_12_001