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

Medicines for Malaria Venture (MMV)

Status and phase: Terminated; Phase 1

Conditions: Malaria

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

Study type: Interventional

Funder types: Other

Identifiers

NCT01615822

MMV_OZ439_12_001

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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25 participants in 5 patient groups, including a placebo group

OZ439 100mg single dose

Experimental group

Description:

OZ439 100mg single dose oral suspension

Treatment:

Drug: OZ439 100mg

OZ439 100mg plus MQ 250mg single doses

Experimental group

Description:

Single dose OZ439 100mg oral suspension in combination with single dose MQ 250mg tablet

Treatment:

Drug: OZ439 100mg

Drug: MQ 250 mg, single dose

OZ439 400mg single dose

Experimental group

Description:

OZ439 400mg single dose oral suspension

Treatment:

Drug: OZ439 400mg

OZ439 400mg plus MQ 750mg single doses

Experimental group

Description:

Single dose OZ439 400mg oral suspension in combination with single dose MQ 750mg tablets

Treatment:

Drug: OZ439 400mg

Drug: MQ 750mg, single dose

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo