Safety Tolerability & Pharmacokinetics of Co-administered Single Doses of OZ439 & Piperaquine to Healthy Subjects

Study Overview
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Brief Summary
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A Phase I Study to investigate the safety, tolerability & pharmacokinetics of co-administered single doses of OZ439 and Piperaquine to healthy subjects.

Detailed Description
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Placebo-controlled, double-blind, five-cohort, 2-period (per cohort) dose-escalation study. For each subject, the study included a screening evaluation (within 21 days of the 1st dose), dosing on 2 separate occasions (Period 1 and Period 2) and a follow-up visit (6 weeks following the final dose). Within each cohort, subjects were randomised into two sequences to receive OZ439 in Period 1 and OZ439 plus piperaquine in Period 2 (sequence 1, 8 subjects) or OZ439-matching placebo in Period 1 and OZ439/piperaquine matching placebos in Period 2 (sequence 2, 4 subjects). Safety and tolerability were evaluated: Physical examination, ECG assessments including a full baseline matched profile of ECG tracings, vital signs, laboratory evaluations, in particular liver function tests and adverse events.

Official Title
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A Phase I Study to Investigate the Safety, Tolerability & Pharmacokinetics of Co-administered Single Doses of OZ439 and Piperaquine to Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: 100mg OZ439 single oral dose
* Drug: Placebo
* Drug: 300 mg OZ439 single oral dose
* Drug: 160mg Piperaquine single oral dose
* Drug: 480mg Piperaquine single oral dose
* Drug: 1440mg Piperaquine single oral dose
* Drug: 800 mg OZ439 single oral dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males & females, 18-55 years old BMI 18 to 30kg/m2; total body weight >50kg Healthy, determined by pre-study medical history, physical examination vital signs, 12 Lead ECG Females of non-childbearing potential. Males must agree to use a double barrier method of contraception Lab tests at screening within the reference ranges Exclusion Criteria: Any condition that could affect drug absorption, e.g. gastrectomy, diarrhea Clinically relevant abnormalities in ECG Family history of sudden death or of congenital prolongation of QTc interval - History of symptomatic cardiac arrhythmias or with clinically relevant bradycardia Electrolyte disturbances History of drug or alcohol abuse, tobacco users Participation in evaluation of any drug for 3 months before the study Administration of ANY systemic medication/herbal product within 14 days of first dose of study drug. unaccustomed strenuous exercise within 7 days of any study visit Alcohol consumption within 24 hours of any study visit Consumption of any fruit juice or food containing grapefruit within 7 days Positive test for HIV-1, HBsAg or HCV Positive urine drug screen at Screening or admission Severe allergies/multiple drug allergies Volunteers who have donated blood or experienced significant blood loss within 90 days of screening Hemoglobin below lower limit of the reference range Clinically relevant abnormal lab values indicative of physical illness

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OZ439 100mg<br>100mg OZ439 single oral dose | Drug: 100mg OZ439 single oral dose<br>* 100mg OZ439 oral suspension single dose<br>* Other names: OZ439;|
| Experimental: OZ439 100 mg + PQP 160mg<br>100mg OZ439 single oral dose + 160mg Piperaquine single oral dose | Drug: 100mg OZ439 single oral dose<br>* 100mg OZ439 oral suspension single dose<br>* Other names: OZ439;Drug: 160mg Piperaquine single oral dose<br>* 160 mg Piperaquine tablet<br>* Other names: Piperaquine;|
| Experimental: OZ439 100 mg + PQP 480mg<br>100mg OZ439 single oral dose + 480mg Piperaquine single oral dose | Drug: 100mg OZ439 single oral dose<br>* 100mg OZ439 oral suspension single dose<br>* Other names: OZ439;Drug: 480mg Piperaquine single oral dose<br>* 480 mg Piperaquine tablet<br>* Other names: Piperaquine;|
| Experimental: OZ439 100 mg + PQP 1440mg<br>100mg OZ439 single oral dose + 1440mg Piperaquine single oral dose | Drug: 100mg OZ439 single oral dose<br>* 100mg OZ439 oral suspension single dose<br>* Other names: OZ439;Drug: 1440mg Piperaquine single oral dose<br>* 1440 mg Piperaquine tablet<br>* Other names: Piperaquine;|
| Experimental: OZ439 300mg<br>300mg OZ439 single oral dose | Drug: 300 mg OZ439 single oral dose<br>* 300mg OZ439 oral suspension single dose<br>* Other names: OZ439;|
| Experimental: OZ439 300 mg + PQP 1440mg<br>300mg OZ439 single oral dose + 1440mg Piperaquine single oral dose | Drug: 300 mg OZ439 single oral dose<br>* 300mg OZ439 oral suspension single dose<br>* Other names: OZ439;Drug: 1440mg Piperaquine single oral dose<br>* 1440 mg Piperaquine tablet<br>* Other names: Piperaquine;|
| Experimental: OZ439 800mg<br>800mg OZ439 single oral dose | Drug: 800 mg OZ439 single oral dose<br>* 800mg OZ439 oral suspension single dose<br>* Other names: OZ439;|
| Experimental: OZ439 800 mg + PQP 1440mg<br>800mg OZ439 single oral dose + 1440mg Piperaquine single oral dose | Drug: 1440mg Piperaquine single oral dose<br>* 1440 mg Piperaquine tablet<br>* Other names: Piperaquine;Drug: 800 mg OZ439 single oral dose<br>* 800mg OZ439 oral suspension single dose<br>* Other names: OZ439;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OZ439 Cmax | OZ439 Maximum concentration level | Up to 168 hours post-dose | 
| Piperaquine Cmax | Piperaquine Maximum concentration level | Up to 1008 hours post-dose (Day 43) | 
| OZ439 AUC(0-168) | Area under the plasma concentration versus time curve to 168 hours post-dose. | Up to 168 hours post-dose | 
| OZ439 t1/2 | OZ439 Elimination half-life | Up to 168 hours post-dose | 
| Piperaquine AUC(0-168) | Piperaquine area under the plasma concentration versus time curve to 168 hours post-dose | Up to 1008 hours post-dose (Day 43) | 
| Piperaquine t1/2 | Piperaquine Elimination half-life (t1/2). | Up to 1008 hours post-dose (Day 43) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Volunteers