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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: 100mg OZ439 single oral dose; Drug: Placebo; Drug: 300 mg OZ439 single oral dose; Drug: 800 mg OZ439 single oral dose; Drug: 1440mg Piperaquine single oral dose; Drug: 160mg Piperaquine single oral dose; Drug: 480mg Piperaquine single oral dose

• Registration Number: NCT01660022
• Lead Sponsor: Medicines for Malaria Venture

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2012-08-06
• Study First Submitted QC: 2012-08-07
• Study First Posted: 2012-08-08
• Study Start: 2012-09
• Primary Completion: 2013-05
• Study Completion: 2013-05
• Results First Submitted: 2014-12-15
• Status Verified: 2015-01
• Results First Submitted QC: 2015-01-07
• Last Update Submitted: 2015-01-07
• Results First Posted: 2015-01-21
• Last Update Posted: 2015-01-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
OZ439 100 mg + PQP 160mg	100mg OZ439 single oral dose	100mg OZ439 single oral dose + 160mg Piperaquine single oral dose
Placebo	Placebo	Placebo
OZ439 100 mg + PQP 1440mg	100mg OZ439 single oral dose	100mg OZ439 single oral dose + 1440mg Piperaquine single oral dose
OZ439 300mg	300 mg OZ439 single oral dose	300mg OZ439 single oral dose
OZ439 100 mg + PQP 1440mg	1440mg Piperaquine single oral dose	100mg OZ439 single oral dose + 1440mg Piperaquine single oral dose
OZ439 800mg	800 mg OZ439 single oral dose	800mg OZ439 single oral dose
OZ439 100mg	100mg OZ439 single oral dose	100mg OZ439 single oral dose
OZ439 100 mg + PQP 160mg	160mg Piperaquine single oral dose	100mg OZ439 single oral dose + 160mg Piperaquine single oral dose
OZ439 100 mg + PQP 480mg	100mg OZ439 single oral dose	100mg OZ439 single oral dose + 480mg Piperaquine single oral dose
OZ439 300 mg + PQP 1440mg	300 mg OZ439 single oral dose	300mg OZ439 single oral dose + 1440mg Piperaquine single oral dose
OZ439 100 mg + PQP 480mg	480mg Piperaquine single oral dose	100mg OZ439 single oral dose + 480mg Piperaquine single oral dose
OZ439 300 mg + PQP 1440mg	1440mg Piperaquine single oral dose	300mg OZ439 single oral dose + 1440mg Piperaquine single oral dose
OZ439 800 mg + PQP 1440mg	1440mg Piperaquine single oral dose	800mg OZ439 single oral dose + 1440mg Piperaquine single oral dose
OZ439 800 mg + PQP 1440mg	800 mg OZ439 single oral dose	800mg OZ439 single oral dose + 1440mg Piperaquine single oral dose

Primary Outcome Measures

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

Trial Locations

Locations (1)

Cross Research S.A.; 🇨🇭 Mendrisio, Switzerland