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

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

Conditions
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Malaria

Intervention / Treatment
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* Drug: OZ439 100mg
* Drug: OZ439 400mg
* Drug: MQ 250 mg, single dose
* Drug: MQ 750mg, single dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malaria, PK, OZ439, Mefloquine, Healthy Volunteers