OZ439 PhIIa Study in Plasmodium Falciparum: Extended Observation

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Medicines for Malaria Venture
Sponsor:
Information provided by (Responsible Party):
Medicines for Malaria Venture
ClinicalTrials.gov Identifier:
NCT01713621
First received: October 22, 2012
Last updated: March 7, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Malaria
Drug: OZ439
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Medicines for Malaria Venture:

Primary Outcome Measures:
  • Minimum Inhibitory Concentration (MIC) [ Time Frame: up to 28 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: March 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OZ439 Dose level 1 (100mg)
Single dose of 100mg of OZ439 administered as an oral suspension
Drug: OZ439
OZ439 is a novel synthetic trioxolane antimalarial agent
Experimental: OZ439 Dose level 2
Single dose (dose level to be confirmed) of OZ439 administered as an oral suspension
Drug: OZ439
OZ439 is a novel synthetic trioxolane antimalarial agent
Experimental: OZ439 dose level 3
Single dose (dose level to be confirmed) of OZ439 administered as an oral suspension
Drug: OZ439
OZ439 is a novel synthetic trioxolane antimalarial agent
Experimental: OZ439 dose level 4
Single dose (dose level to be confirmed) of OZ439 administered as an oral suspension
Drug: OZ439
OZ439 is a novel synthetic trioxolane antimalarial agent

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01713621

Contacts
Contact: Sasithon Pukrittayakamee, MD yon@tropmedres.ac

Locations
Thailand
Mae Ramat District hospital Not yet recruiting
Mae Ramat, Tak, Thailand, 63140
Contact: Uthaisin Chirapong, MD         
Principal Investigator: Uthaisin Chirapong, MD         
Shoklo Malaria Research Unit Recruiting
Mae Sot, Tak, Thailand, 63110
Contact: Francois Nosten, MD       francois@tropmedres.ac   
Principal Investigator: Francois Nosten, MD         
Sub-Investigator: Aung P Phyo, MD         
Sub-Investigator: Cindy Chu, MD         
Faculty of Tropical Medicine, Active, not recruiting
Bangkok, Thailand, 10400
Sponsors and Collaborators
Medicines for Malaria Venture
Investigators
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
  More Information

Additional Information:
Publications:
Responsible Party: Medicines for Malaria Venture
ClinicalTrials.gov Identifier: NCT01713621     History of Changes
Other Study ID Numbers: MMV_OZ439_12_006
Study First Received: October 22, 2012
Last Updated: March 7, 2014
Health Authority: Thailand: Food and Drug Administration

Keywords provided by Medicines for Malaria Venture:
P. falciparum
malaria

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on September 22, 2014