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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: 100mg OZ439 single oral dose; Drug: 160mg Piperaquine single oral dose; Drug: 480mg Piperaquine single oral dose; Drug: 1440mg Piperaquine single oral dose; Drug: 300 mg OZ439 single oral dose; Drug: 800 mg OZ439 single oral dose

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 Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Mendrisio, Switzerland, CH 6850
    • Cross Research S.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: OZ439 100mg; 100mg OZ439 single oral dose	Drug: 100mg OZ439 single oral dose; 100mg OZ439 oral suspension single dose; Other Names: OZ439
Experimental: OZ439 100 mg + PQP 160mg; 100mg OZ439 single oral dose + 160mg Piperaquine single oral dose	Drug: 100mg OZ439 single oral dose; 100mg OZ439 oral suspension single dose; Other Names: OZ439; Drug: 160mg Piperaquine single oral dose; 160 mg Piperaquine tablet; Other Names: Piperaquine
Experimental: OZ439 100 mg + PQP 480mg; 100mg OZ439 single oral dose + 480mg Piperaquine single oral dose	Drug: 100mg OZ439 single oral dose; 100mg OZ439 oral suspension single dose; Other Names: OZ439; Drug: 480mg Piperaquine single oral dose; 480 mg Piperaquine tablet; Other Names: Piperaquine
Experimental: OZ439 100 mg + PQP 1440mg; 100mg OZ439 single oral dose + 1440mg Piperaquine single oral dose	Drug: 100mg OZ439 single oral dose; 100mg OZ439 oral suspension single dose; Other Names: OZ439; Drug: 1440mg Piperaquine single oral dose; 1440 mg Piperaquine tablet; Other Names: Piperaquine
Experimental: OZ439 300mg; 300mg OZ439 single oral dose	Drug: 300 mg OZ439 single oral dose; 300mg OZ439 oral suspension single dose; Other Names: OZ439
Experimental: OZ439 300 mg + PQP 1440mg; 300mg OZ439 single oral dose + 1440mg Piperaquine single oral dose	Drug: 1440mg Piperaquine single oral dose; 1440 mg Piperaquine tablet; Other Names: Piperaquine; Drug: 300 mg OZ439 single oral dose; 300mg OZ439 oral suspension single dose; Other Names: OZ439
Experimental: OZ439 800mg; 800mg OZ439 single oral dose	Drug: 800 mg OZ439 single oral dose; 800mg OZ439 oral suspension single dose; Other Names: OZ439
Experimental: OZ439 800 mg + PQP 1440mg; 800mg OZ439 single oral dose + 1440mg Piperaquine single oral dose	Drug: 1440mg Piperaquine single oral dose; 1440 mg Piperaquine tablet; Other Names: Piperaquine; Drug: 800 mg OZ439 single oral dose; 800mg OZ439 oral suspension single dose; Other Names: OZ439

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Medicines for Malaria Venture
• Collaborators: Cross Research S.A.
• Investigators: Principal Investigator: Milko M Radicioni, MD PhD, Cross Research S.A.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: August 6, 2012
• First Submitted That Met QC Criteria: August 7, 2012
• First Posted (Estimate): August 8, 2012

Study Record Updates

• Last Update Posted (Estimate): January 21, 2015
• Last Update Submitted That Met QC Criteria: January 7, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Healthy; Volunteers
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Piperaquine; Artefenomel
• Other Study ID Numbers: MMV_OZ439_12_002