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

June 7, 2012
March 17, 2015
August 2012
April 2013   (final data collection date for primary outcome measure)
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
Area under the plasma concentration versus time curve (AUC) of OZ439 [ Time Frame: Up to 42 days post-dose ] [ Designated as safety issue: No ]

Period 1 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h and 96h post-dose.

Period 2 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

Period 3 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

Complete list of historical versions of study NCT01615822 on ClinicalTrials.gov Archive Site
  • 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
  • Peak Plasma Concentration (Cmax) of OZ439 [ Time Frame: Up to 42 days post-dose ] [ Designated as safety issue: No ]

    Period 1 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h and 96h post-dose.

    Period 2 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

    Period 3 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

  • Tmax (the time to reach Cmax after drug ingestion) for OZ439 [ Time Frame: Up to 42 days post-dose ] [ Designated as safety issue: No ]

    Period 1 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h and 96h post-dose.

    Period 2 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

    Period 3 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

  • T½ (half-life) of OZ439 [ Time Frame: Up to 42 days post-dose ] [ Designated as safety issue: No ]

    Period 1 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h and 96h post-dose.

    Period 2 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

    Period 3 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

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

    Period 1 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h and 96h post-dose.

    Period 2 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

    Period 3 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

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

    Period 1 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h and 96h post-dose.

    Period 2 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

    Period 3 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

  • Tmax (the time to reach Cmax after drug ingestion) for MQ [ Time Frame: Day 42 post-dose ] [ Designated as safety issue: No ]

    Period 1 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h and 96h post-dose.

    Period 2 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

    Period 3 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

  • T½ (half-life) of MQ [ Time Frame: Day 42 post-dose ] [ Designated as safety issue: No ]

    Period 1 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h and 96h post-dose.

    Period 2 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

    Period 3 Predose (-0.5h to 0h), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 16h, 24h, 36h, 48h, 72h, 96h, 168h, 240h, 336h, Day 28, Day 35 and Day 42 post-dose.

Not Provided
Not Provided
 
Safety, Tolerability & Pharmacokinetics (PK) of Co-administered Single Doses of OZ439 and Mefloquine (MQ) in Healthy Volunteers
A Phase I Healthy Volunteer Study Investigating the Safety, Tolerability & Pharmacokinetics of Co-administered Single Doses of OZ439 and Mefloquine

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Malaria
  • Drug: OZ439 100mg
    OZ439 100mg oral suspension, single dose
  • Drug: OZ439 400mg
    OZ439 400mg oral suspension, single dose
  • Drug: MQ 250 mg, single dose
    Mefloquine 250 mg tablet, single dose
  • Drug: MQ 750mg, single dose
    Mefloquine 750mg oral tablet, single dose
  • Drug: Placebo
  • Experimental: OZ439 100mg single dose
    OZ439 100mg single dose oral suspension
    Intervention: Drug: OZ439 100mg
  • Experimental: OZ439 100mg plus MQ 250mg single doses
    Single dose OZ439 100mg oral suspension in combination with single dose MQ 250mg tablet
    Interventions:
    • Drug: OZ439 100mg
    • Drug: MQ 250 mg, single dose
  • Experimental: OZ439 400mg single dose
    OZ439 400mg single dose oral suspension
    Intervention: Drug: OZ439 400mg
  • Experimental: OZ439 400mg plus MQ 750mg single doses
    Single dose OZ439 400mg oral suspension in combination with single dose MQ 750mg tablets
    Interventions:
    • Drug: OZ439 400mg
    • Drug: MQ 750mg, single dose
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
25
April 2013
April 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
South Africa
 
NCT01615822
MMV_OZ439_12_001
Yes
Medicines for Malaria Venture
Medicines for Malaria Venture
University of Cape Town
Principal Investigator: Karen I Barnes University of Cape Town
Medicines for Malaria Venture
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP