A Healthy Volunteer Study of Safety, Tolerability & PK of Co-administered Single Doses of OZ439 and Mefloquine

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: July 18, 2013
Last verified: July 2013

June 7, 2012
July 18, 2013
August 2012
April 2013   (final data collection date for primary outcome measure)
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.

Same as current
Complete list of historical versions of study NCT01615822 on ClinicalTrials.gov Archive Site
  • 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.

Same as current
Not Provided
Not Provided
 
A Healthy Volunteer Study of Safety, Tolerability & PK of Co-administered Single Doses of OZ439 and Mefloquine
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 y mg
    OZ439 y mg oral suspension, single dose
  • Drug: OZ439 z mg, single dose
    OZ439 z mg oral suspension single dose. Dose to be determined based on PK data for previous cohort.
  • Drug: MQ 250 mg, single dose
    Mefloquine 250 mg tablet, single dose
  • Drug: MQ a mg, single dose
    Mefloquine b mg oral tablet, single dose. Dose to be determined based on PK data for previous cohort.
  • Drug: MQ b mg, single dose
    Mefloquine b mg tablet single dose. Dose to be determined based on PK data for previous cohort.
  • Drug: placebo to OZ439
    Placebo to OZ439 oral suspension single dose.
  • Drug: placebo to MQ
    placebo to Mefloquine tablet, single dose
  • Experimental: OZ439 single dose
    Interventions:
    • Drug: OZ439 100mg
    • Drug: OZ439 y mg
    • Drug: OZ439 z mg, single dose
  • Placebo Comparator: placebo to OZ439 single dose
    Intervention: Drug: placebo to OZ439
  • Experimental: OZ439 plus MQ single doses
    Interventions:
    • Drug: OZ439 y mg
    • Drug: OZ439 z mg, single dose
    • Drug: MQ 250 mg, single dose
    • Drug: MQ a mg, single dose
    • Drug: MQ b mg, single dose
  • Experimental: OZ439 plus MQ placebo single doses
    Intervention: Drug: placebo to MQ
  • Experimental: OZ439 placebo plus MQ single doses
    Interventions:
    • Drug: MQ 250 mg, single dose
    • Drug: MQ a mg, single dose
    • Drug: MQ b mg, single dose
    • Drug: placebo to OZ439
  • Placebo Comparator: OZ439 placebo & MQ placebo single doses
    Interventions:
    • Drug: placebo to OZ439
    • Drug: placebo to MQ
  • Experimental: MQ single dose
    Intervention: Drug: MQ b mg, single dose
  • Placebo Comparator: MQ placebo sd
    Intervention: Drug: placebo to MQ
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
24
April 2013
April 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Written informed consent prior to any study procedures
  • Healthy male and non-childbearing potential female volunteers of between 18 and 55 years of age, as determined by pre-study medical history, physical examination (including body temperature and a 12-lead ECG). Subjects must have no history of cardiovascular disease or conduction abnormality
  • Female volunteers must have a negative serum pregnancy test at screening
  • Females must be of non-childbearing potential, i.e. surgically sterilized, or post-menopausal (amenorrhea for at least 1 year and confirmed by follicle stimulating hormone [FSH] levels)
  • Male volunteers and their partner(s) must agree to use a double barrier method of contraception including condom plus diaphragm/IUD/stable oral/transdermal/injectable hormonal contraceptive by female partner for at least 14 days prior to first dose of study drug through 90 days after the last dose. Abstinent volunteers agree starting a double barrier method if they start sexual relationships during the study and up to 90 days after the last dose of either study drug
  • Body mass Index between 18 and 30kg/m2, inclusive; and a total body weight >50 kg
  • Laboratory tests at screening within normal ranges or if outside the normal range not clinically significant as judged by the Investigator and confirmed and agreed by the sponsor. For Liver Function Tests, AST, ALT or conjugated bilirubin must be <1.5xULN for the subject to be included.

Exclusion Criteria:

  • A diagnosis of Plasmodium falciparum, vivax, ovale, malariae, or knowlesi malaria, confirmed by a malaria rapid diagnostic antigen test and/ or thick blood smear
  • General:
  • 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, haematologic, metabolic, neurological, immunologic, nephrologic, endocrine, psychiatric disease, or clinically significant current infection.
  • Pharmacokinetic:
  • Evidence of current or history of clinically significant gastrointestinal (excluding appendectomy, cholecystectomy) disease
  • 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, or consumption of >2 units alcohol in any one day or consumption of >15 units alcohol in any one week throughout the study
  • Tobacco users (includes stopping smoking up to 90 days prior to the screening evaluation). Tobacco use includes smoking and use of snuff and nicotine containing products
  • Consumption of fruit juices within 7 days prior to dosing with study drug
  • Participation in unaccustomed strenuous exercise within 7 days prior to
  • Screening or within 7 days prior to dosing of the study drug.
  • Positive urine drug screen (cocaine, amphetamine, opioids, cannabis, benzodiazepine) at Screening
  • Positive test for HIV-1, HBsAg or HCV
  • Contraindication to the study drugs
  • Known hypersensitivity to MQ or artemisinins
  • QTc greater than 450msec as corrected by the Fridericia's formula
  • Any personal or family history of suicidal behavior or suicidality or depression, psychosis, anxiety disorder, schizophrenia, or other major psychiatric disorder
  • History of seizures
  • Suicidal behavior or any suicidal ideation using Columbia Suicide Severity rating Scale
  • Current low mood or behaviour changes, anxiety, depression, feelings of persecution, crying, aggression, forgetfulness, agitation, confusion or hallucinations (using QIDS)
  • Current parasomnia based on ICSD criteria and screening by interview.
  • Includes confusional arousals, sleepwalking, sleep terrors, nightmares, sleep paralysis, sleep related hallucinations and dream enactment (REM behavioural disorder)
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
July 2013

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