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

Medicines for Malaria Venture (MMV)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: 800 mg OZ439 single oral dose; Drug: 160mg Piperaquine single oral dose; Drug: 480mg Piperaquine single oral dose; Drug: 100mg OZ439 single oral dose; Drug: 1440mg Piperaquine single oral dose; Drug: Placebo; Drug: 300 mg OZ439 single oral dose

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01660022

MMV_OZ439_12_002

Details and patient eligibility

About

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

Full 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.

Enrollment: 59 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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59 participants in 9 patient groups, including a placebo group

OZ439 100mg

Experimental group

Description:

100mg OZ439 single oral dose

Treatment:

Drug: 100mg OZ439 single oral dose

OZ439 100 mg + PQP 160mg

Experimental group

Description:

100mg OZ439 single oral dose + 160mg Piperaquine single oral dose

Treatment:

Drug: 100mg OZ439 single oral dose

Drug: 160mg Piperaquine single oral dose

OZ439 100 mg + PQP 480mg

Experimental group

Description:

100mg OZ439 single oral dose + 480mg Piperaquine single oral dose

Treatment:

Drug: 100mg OZ439 single oral dose

Drug: 480mg Piperaquine single oral dose

OZ439 100 mg + PQP 1440mg

Experimental group

Description:

100mg OZ439 single oral dose + 1440mg Piperaquine single oral dose

Treatment:

Drug: 1440mg Piperaquine single oral dose

Drug: 100mg OZ439 single oral dose

OZ439 300mg

Experimental group

Description:

300mg OZ439 single oral dose

Treatment:

Drug: 300 mg OZ439 single oral dose

OZ439 300 mg + PQP 1440mg

Experimental group

Description:

300mg OZ439 single oral dose + 1440mg Piperaquine single oral dose

Treatment:

Drug: 300 mg OZ439 single oral dose

Drug: 1440mg Piperaquine single oral dose

OZ439 800mg

Experimental group

Description:

800mg OZ439 single oral dose

Treatment:

Drug: 800 mg OZ439 single oral dose

OZ439 800 mg + PQP 1440mg

Experimental group

Description:

800mg OZ439 single oral dose + 1440mg Piperaquine single oral dose

Treatment:

Drug: 1440mg Piperaquine single oral dose

Drug: 800 mg OZ439 single oral dose

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo