OZ439 PhIIa Study in Plasmodium Falciparum: Extended Observation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01713621
Recruitment Status : Completed
First Posted : October 25, 2012
Results First Posted : February 10, 2017
Last Update Posted : April 14, 2017
Information provided by (Responsible Party):
Medicines for Malaria Venture

Brief Summary:
This study aims to investigate the concentration dependent effects of OZ439 on the clearance of P. falciparum parasites in patients, specifically the determination of an in-vivo minimum inhibitory concentration (MIC) of OZ439. Characterisation of PK-PD (Pharmacokinetic-Pharmacodynamic) relationships is essential for rational evidence based dosing. The adaptive investigation of a range of doses will provide the best chance of accurate PK-PD characterisation, allowing the observation of Plasmodium falciparum growth dynamics and the subsequent identification of MIC and MPC (minimum parasiticidal concentration). Additionally the tolerability and pharmacokinetics of OZ439 will be confirmed. The PK/PD relationship between OZ439 exposure and subsequent effects on parasitaemia will be investigated.

Condition or disease Intervention/treatment Phase
Malaria Drug: OZ439 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Extended Observation Over a Period of 28 Days of the Effects of Single Doses of OZ439 on the Recrudescence of Plasmodium Falciparum Malaria - a PhIIa, Open Label Study in Adult Patients
Study Start Date : March 2013
Actual Primary Completion Date : April 2015
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria
U.S. FDA Resources

Arm Intervention/treatment
Experimental: OZ439 100mg
Single dose of 100mg of OZ439 administered as an oral suspension
Drug: OZ439
OZ439 is a novel synthetic trioxolane antimalarial agent
Experimental: OZ439 500mg
Single dose of 500mg of OZ439 administered as an oral suspension
Drug: OZ439
OZ439 is a novel synthetic trioxolane antimalarial agent

Primary Outcome Measures :
  1. Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration (MPC) [ Time Frame: up to 28 days ]
    The estimated MIC and MPC were derived from the fitted parasitaemia concentration and PK/PD relationship.

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female patients between the age of 18 and 60 years, inclusive
  2. Body weight between 45 kg and 90 kg inclusive
  3. Presence of mono-infection of P. falciparum confirmed by:

    1. Fever, as defined by axillary temperature ≥ 37.5°C or oral/rectal/tympanic temperature ≥ 38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,
    2. Microscopically confirmed parasite infection: 1,000 to 75,000 asexual parasite count/µL blood.
  4. Written informed consent, in accordance with local practice, provided by patient. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations
  5. Ability to swallow oral medication
  6. Ability and willingness to participate and access the health facility
  7. Agree to hospitalization for at least 72h until parasites have fallen below the level of polymerase chain reaction (PCR) detection and have no signs or symptoms of malaria; and then to return once daily to the study centre for blood sampling for quantitative polymerase chain reaction (qPCR), and rehospitalisation when qPCR levels are detectable.

Exclusion Criteria:

  1. Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization Criteria 2010
  2. Mixed Plasmodium infection
  3. Severe vomiting, defined as more than three times in the 24 hours prior to inclusion in the study or inability to tolerate oral treatment, or severe diarrhoea defined as 3 or more watery stools per day
  4. Presence of other serious or chronic clinical condition requiring hospitalization
  5. Severe malnutrition (defined as the weight-for-height being below -3 standard deviation or less than 70% of median of the NCHS/WHO normalized reference values)
  6. Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval greater than or equal to 450 msec), respiratory (including active tuberculosis), history of jaundice, hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric, history of convulsions or other abnormality (including head trauma)
  7. Known history of hypersensitivity, allergic or adverse reactions to artemisinin containing compounds or mefloquine
  8. Known active Hepatitis A Immunoglobulin M (IgM) (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab)
  9. Have received any antimalarial treatment in the preceding 14 days, as determined by history and screening test
  10. Have received antibacterial with known antimalarial activity in the preceding 14 days
  11. Have received an investigational drug within the past 4 weeks
  12. Liver function tests (Aspartate Aminotransferase(ASAT)/Alanine Aminotransferase (ALAT) levels) > 2x upper limit of normal (ULN) if Total Bilirubin normal or >1.5xULN if Total bilirubin between >1 and >1.5xULN
  13. Hemoglobin (Hb) level =< 8g/dl
  14. Total Bilirubin > 1.5XULN
  15. Serum creatinine levels more than 2 times the upper limit of normal range (>2xULN).
  16. Female patients must be neither pregnant as demonstrated by a negative serum pregnancy test at screening and urinary pregnancy test pre-dose (the result of the pre-dose assessment must be confirmed negative prior to dosing) nor lactating, and must be willing to take measures not to become pregnant during the study period and safety follow-up period.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01713621

Mae Ramat District hospital
Mae Ramat, Tak, Thailand, 63140
Shoklo Malaria Research Unit
Mae Sot, Tak, Thailand, 63110
Faculty of Tropical Medicine,
Bangkok, Thailand, 10400
Sponsors and Collaborators
Medicines for Malaria Venture
Principal Investigator: Sasithon Pukrittayakamee, MD Faculty of Tropical Medicine, Mahidol University, Bangkok
Principal Investigator: Francois Nosten, MD Shoklo Malaria Research Unit, Faculty of Tropical medicine, Mahidol University

Additional Information:
Responsible Party: Medicines for Malaria Venture Identifier: NCT01713621     History of Changes
Other Study ID Numbers: MMV_OZ439_12_006
First Posted: October 25, 2012    Key Record Dates
Results First Posted: February 10, 2017
Last Update Posted: April 14, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Medicines for Malaria Venture:
P. falciparum

Additional relevant MeSH terms:
Protozoan Infections
Parasitic Diseases