Clinical trial NCT01660022: Safety Tolerability & Pharmacokinetics of Co-administered Single Doses of OZ439 & Piperaquine to Healthy Subjects
Official title: A Phase I Study to Investigate the Safety, Tolerability & Pharmacokinetics of Co-administered Single Doses of OZ439 and Piperaquine to Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Volunteers
Lead sponsor: Medicines for Malaria Venture
Sponsor class: OTHER
Collaborators: name: Cross Research S.A.
First posted: 2012-08-08
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: OZ439 Cmax
timeFrame: Up to 168 hours post-dose
measure: Piperaquine Cmax
timeFrame: Up to 1008 hours post-dose (Day 43)
measure: OZ439 AUC(0-168)
timeFrame: Up to 168 hours post-dose
measure: OZ439 t1/2
timeFrame: Up to 168 hours post-dose
measure: Piperaquine AUC(0-168)
timeFrame: Up to 1008 hours post-dose (Day 43)
measure: Piperaquine t1/2
timeFrame: Up to 1008 hours post-dose (Day 43)
Secondary outcomes:
Other outcomes:
Locations:
city: Mendrisio
country: Switzerland
facility: Cross Research S.A.
Study officials:
affiliation: Cross Research S.A.
name: Milko M Radicioni, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: