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

Phase 1

Terminated

Interventions: Drug: OZ439 100mg
Drug: OZ439 400mg
Drug: Placebo
Drug: MQ 250 mg, single dose
Drug: MQ 750mg, single dose

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
OZ439 100mg plus MQ 250mg single doses	OZ439 100mg	Single dose OZ439 100mg oral suspension in combination with single dose MQ 250mg tablet
OZ439 400mg single dose	OZ439 400mg	OZ439 400mg single dose oral suspension
OZ439 400mg plus MQ 750mg single doses	OZ439 400mg	Single dose OZ439 400mg oral suspension in combination with single dose MQ 750mg tablets
OZ439 100mg single dose	OZ439 100mg	OZ439 100mg single dose oral suspension
OZ439 100mg plus MQ 250mg single doses	MQ 250 mg, single dose	Single dose OZ439 100mg oral suspension in combination with single dose MQ 250mg tablet
OZ439 400mg plus MQ 750mg single doses	MQ 750mg, single dose	Single dose OZ439 400mg oral suspension in combination with single dose MQ 750mg tablets
Placebo	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
OZ439 AUC0-t	Up to 42 days post-dose	Area under the plasma concentration versus time curve (AUC) of OZ439

Secondary Outcome Measures

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