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

This study has been terminated.
(Decision taken to halt progression of mefloquine as a potential partner for OZ439 as a single dose cure due to low probability of success)
Sponsor:
Collaborator:
University of Cape Town
Information provided by (Responsible Party):
Medicines for Malaria Venture
ClinicalTrials.gov Identifier:
NCT01615822
First received: June 7, 2012
Last updated: March 17, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Malaria
Drug: OZ439 100mg
Drug: OZ439 400mg
Drug: MQ 250 mg, single dose
Drug: MQ 750mg, single dose
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase I Healthy Volunteer Study Investigating the Safety, Tolerability & Pharmacokinetics of Co-administered Single Doses of OZ439 and Mefloquine

Resource links provided by NLM:


Further study details as provided by Medicines for Malaria Venture:

Primary Outcome Measures:
  • OZ439 AUC0-t [ Time Frame: Up to 42 days post-dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration versus time curve (AUC) of OZ439


Secondary Outcome Measures:
  • OZ439 Cmax [ Time Frame: Up to 42 days post-dose ] [ Designated as safety issue: No ]
    Peak Plasma Concentration (Cmax) of OZ439

  • MQ AUC0-t [ Time Frame: Up to 42 days post-dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration versus time curve (AUC) of MQ

  • MQ Cmax [ Time Frame: Up to 42 days post-dose ] [ Designated as safety issue: No ]
    Peak Plasma Concentration (Cmax) of MQ


Enrollment: 25
Study Start Date: August 2012
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OZ439 100mg single dose
OZ439 100mg single dose oral suspension
Drug: OZ439 100mg
OZ439 100mg oral suspension, single dose
Experimental: OZ439 100mg plus MQ 250mg single doses
Single dose OZ439 100mg oral suspension in combination with single dose MQ 250mg tablet
Drug: OZ439 100mg
OZ439 100mg oral suspension, single dose
Drug: MQ 250 mg, single dose
Mefloquine 250 mg tablet, single dose
Experimental: OZ439 400mg single dose
OZ439 400mg single dose oral suspension
Drug: OZ439 400mg
OZ439 400mg oral suspension, single dose
Experimental: OZ439 400mg plus MQ 750mg single doses
Single dose OZ439 400mg oral suspension in combination with single dose MQ 750mg tablets
Drug: OZ439 400mg
OZ439 400mg oral suspension, single dose
Drug: MQ 750mg, single dose
Mefloquine 750mg oral tablet, single dose
Placebo Comparator: Placebo
Placebo
Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01615822

Locations
South Africa
Division of Clinical Pharmacology, University of Cape Town
Cape Town, South Africa, 7925
Sponsors and Collaborators
Medicines for Malaria Venture
University of Cape Town
Investigators
Principal Investigator: Karen I Barnes University of Cape Town
  More Information

No publications provided

Responsible Party: Medicines for Malaria Venture
ClinicalTrials.gov Identifier: NCT01615822     History of Changes
Other Study ID Numbers: MMV_OZ439_12_001
Study First Received: June 7, 2012
Results First Received: March 17, 2015
Last Updated: March 17, 2015
Health Authority: South Africa: Medicines Control Council

Keywords provided by Medicines for Malaria Venture:
Malaria
PK
OZ439
Mefloquine
Healthy Volunteers

Additional relevant MeSH terms:
Mefloquine
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on March 26, 2015