Clinical trial NCT01615822: Safety, Tolerability & Pharmacokinetics (PK) of Co-administered Single Doses of OZ439 and Mefloquine (MQ) in Healthy Volunteers
Official title: A Phase I Healthy Volunteer Study Investigating the Safety, Tolerability & Pharmacokinetics of Co-administered Single Doses of OZ439 and Mefloquine
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Malaria
Keywords: Malaria
PK
OZ439
Mefloquine
Healthy Volunteers
Lead sponsor: Medicines for Malaria Venture
Sponsor class: OTHER
Collaborators: name: University of Cape Town
First posted: 2012-06-11
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: OZ439 is a novel, synthetic trioxolane medicine which is related to artemisinin, but has the advantage of a longer elimination half-life so is being developed to be administered together with a potential partner drug e.g. mefloquine as a single dose cure for uncomplicated malaria. The study findings will be used to inform the dose and design of future studies. The aim of the study is to establish the safety, tolerability and pharmacokinetics of co-administered OZ439 and MQ at a range of doses up to the maximum tolerated dose, in healthy volunteers.


Eligibility criteria: Inclusion Criteria:

* Healthy male and non-childbearing potential female volunteers of between 18 and 55 years of age
* Female volunteers must have a negative serum pregnancy test at screening
* Females must be of non-childbearing potential
* Male volunteers and their partner(s) must agree to use a double barrier method of contraception for at least 14 days prior to first dose of study drug through 90 days after the last dose.
* Body mass Index between 18 and 30kg/m2, inclusive; and a total body weight \>50 kg
* Laboratory tests at screening within normal ranges or not clinically significant as judged by the Investigator.

Exclusion Criteria:

* Received an investigational drug or participated in another research study within 30 days of the first dose of study drug or at any time through the study
* Evidence of current or history of clinically significant oncologic, pulmonary, hepatic, cardiovascular, gastrointestinal, haematologic, metabolic, neurological, immunologic, nephrologic, endocrine, psychiatric disease, or clinically significant current infection.
* Any condition that could possibly affect drug absorption, such as gastrectomy, diarrhea and lactose intolerance
* Use of any medications, vitamins, herbal supplements, dietary supplements or vaccinations within 14 days of the first dose of study drug or at any time through the study, unless prior approval is granted. This includes any drugs that are substrates, inhibitors or inducers of CYP3A4. Intermittent use of acetaminophen at doses of up to 2g/day is permitted
* History of drug or alcohol abuse within 2 years of Screening
* History of alcohol consumption within 24 hours of any study visit
* Tobacco users
* Consumption of fruit juices within 7 days prior to dosing
* Participation in unaccustomed strenuous exercise within 7 days prior to
* Positive urine drug screen
* Positive test for HIV-1, HBsAg or HCV
* Known hypersensitivity to MQ or artemisinins
* QTcF greater than 450msec

Primary outcomes:
measure: OZ439 AUC0-t
timeFrame: Up to 42 days post-dose
Secondary outcomes:
measure: OZ439 Cmax
timeFrame: Up to 42 days post-dose
measure: MQ AUC0-t
timeFrame: Up to 42 days post-dose
measure: MQ Cmax
timeFrame: Up to 42 days post-dose
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: Division of Clinical Pharmacology, University of Cape Town
Study officials:
affiliation: University of Cape Town
name: Karen I Barnes
role: PRINCIPAL_INVESTIGATOR
References: