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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01660022
• Other study ID #: MMV_OZ439_12_002
• Status: Completed
• Phase: Phase 1
• First received: August 6, 2012
• Last updated: January 7, 2015
• Start date: September 2012
• Est. completion date: May 2013

Study information

• Verified date: January 2015
• Source: Medicines for Malaria Venture
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• 100mg OZ439 single oral dose
100mg OZ439 oral suspension single dose
• Placebo
Placebo
• 300 mg OZ439 single oral dose
300mg OZ439 oral suspension single dose
• 160mg Piperaquine single oral dose
160 mg Piperaquine tablet
• 480mg Piperaquine single oral dose
480 mg Piperaquine tablet
• 1440mg Piperaquine single oral dose
1440 mg Piperaquine tablet
• 800 mg OZ439 single oral dose
800mg OZ439 oral suspension single dose

Locations

Country	Name	City	State
Switzerland	Cross Research S.A.	Mendrisio

Sponsors (2)

Lead Sponsor	Collaborator
Medicines for Malaria Venture	Cross Research S.A.

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OZ439 Cmax	OZ439 Maximum concentration level	Up to 168 hours post-dose	No
Primary	Piperaquine Cmax	Piperaquine Maximum concentration level	Up to 1008 hours post-dose (Day 43)	No
Primary	OZ439 AUC(0-168)	Area under the plasma concentration versus time curve to 168 hours post-dose.	Up to 168 hours post-dose	No
Primary	OZ439 t1/2	OZ439 Elimination half-life	Up to 168 hours post-dose	No
Primary	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)	No
Primary	Piperaquine t1/2	Piperaquine Elimination half-life (t1/2).	Up to 1008 hours post-dose (Day 43)	No