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

Condition(s) targeted: Malaria

Intervention: OZ439 100mg (Drug); OZ439 400mg (Drug); MQ 250 mg, single dose (Drug); MQ 750mg, single dose (Drug); Placebo (Drug)

Phase: Phase 1

Status: Terminated

Sponsored by: Medicines for Malaria Venture

Official(s) and/or principal investigator(s):
Karen I Barnes, Principal Investigator, Affiliation: University of Cape Town

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: OZ439 AUC0-t

Secondary outcome:

OZ439 Cmax

MQ AUC0-t

MQ Cmax

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

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

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

Starting date: August 2012
Last updated: March 27, 2015