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

NCT ID: NCT01615822

Last Updated: 2015-04-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2013-04-30

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.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

OZ439 100mg single dose

OZ439 100mg single dose oral suspension

Group Type: EXPERIMENTAL

OZ439 100mg

Intervention Type: DRUG

OZ439 100mg oral suspension, single dose

OZ439 100mg plus MQ 250mg single doses

Single dose OZ439 100mg oral suspension in combination with single dose MQ 250mg tablet

Group Type: EXPERIMENTAL

OZ439 100mg

Intervention Type: DRUG

OZ439 100mg oral suspension, single dose

MQ 250 mg, single dose

Intervention Type: DRUG

Mefloquine 250 mg tablet, single dose

OZ439 400mg single dose

OZ439 400mg single dose oral suspension

Group Type: EXPERIMENTAL

OZ439 400mg

Intervention Type: DRUG

OZ439 400mg oral suspension, single dose

OZ439 400mg plus MQ 750mg single doses

Single dose OZ439 400mg oral suspension in combination with single dose MQ 750mg tablets

Group Type: EXPERIMENTAL

OZ439 400mg

Intervention Type: DRUG

OZ439 400mg oral suspension, single dose

MQ 750mg, single dose

Intervention Type: DRUG

Mefloquine 750mg oral tablet, single dose

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

OZ439 100mg

OZ439 100mg oral suspension, single dose

Intervention Type: DRUG

OZ439 400mg

OZ439 400mg oral suspension, single dose

Intervention Type: DRUG

MQ 250 mg, single dose

Mefloquine 250 mg tablet, single dose

Intervention Type: DRUG

MQ 750mg, single dose

Mefloquine 750mg oral tablet, single dose

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Cape Town

OTHER

Sponsor Role: collaborator

Medicines for Malaria Venture

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karen I Barnes

Role: PRINCIPAL_INVESTIGATOR

University of Cape Town

Locations

Division of Clinical Pharmacology, University of Cape Town

Cape Town, , South Africa

Countries

South Africa

Other Identifiers

MMV_OZ439_12_001

Identifier Type: -

Identifier Source: org_study_id