Safety, Tolerability & Pharmacokinetics (PK) of Co-administered Single Doses of OZ439 and Mefloquine (MQ) in Healthy Volunteers

Malaria Clinical Trial

Official title:

A Phase I Healthy Volunteer Study Investigating the Safety, Tolerability & Pharmacokinetics of Co-administered Single Doses of OZ439 and Mefloquine

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01615822
• Other study ID #: MMV_OZ439_12_001
• Status: Terminated
• Phase: Phase 1
• First received: June 7, 2012
• Last updated: March 27, 2015
• Start date: August 2012
• Est. completion date: April 2013

Study information

• Verified date: March 2015
• Source: Medicines for Malaria Venture
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• OZ439 100mg
OZ439 100mg oral suspension, single dose
• OZ439 400mg
OZ439 400mg oral suspension, single dose
• MQ 250 mg, single dose
Mefloquine 250 mg tablet, single dose
• MQ 750mg, single dose
Mefloquine 750mg oral tablet, single dose
• Placebo

Locations

Country	Name	City	State
South Africa	Division of Clinical Pharmacology, University of Cape Town	Cape Town

Sponsors (2)

Lead Sponsor	Collaborator
Medicines for Malaria Venture	University of Cape Town

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OZ439 AUC0-t	Area under the plasma concentration versus time curve (AUC) of OZ439	Up to 42 days post-dose	No
Secondary	OZ439 Cmax	Peak Plasma Concentration (Cmax) of OZ439	Up to 42 days post-dose	No
Secondary	MQ AUC0-t	Area under the plasma concentration versus time curve (AUC) of MQ	Up to 42 days post-dose	No
Secondary	MQ Cmax	Peak Plasma Concentration (Cmax) of MQ	Up to 42 days post-dose	No