OZ439 PhIIa Study in Plasmodium Falciparum: Extended Observation

NCT01713621 | Completed Phase 2 Results

• 1 other identifier: MMV_OZ439_12_006
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

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.

Conditions

Malaria

Keywords

P. falciparum; malaria

Outcome Measures

Primary Outcomes (1)

• Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration (MPC)

  The estimated MIC and MPC were derived from the fitted parasitaemia concentration and PK/PD relationship.

  up to 28 days

Study Arms (2)

OZ439 100mg

EXPERIMENTAL

Single dose of 100mg of OZ439 administered as an oral suspension

Drug: OZ439

OZ439 500mg

EXPERIMENTAL

Single dose of 500mg of OZ439 administered as an oral suspension

Drug: OZ439

Interventions

OZ439 DRUG

OZ439 is a novel synthetic trioxolane antimalarial agent

OZ439 100mg; OZ439 500mg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female patients between the age of 18 and 60 years, inclusive
• Body weight between 45 kg and 90 kg inclusive
• Presence of mono-infection of P. falciparum confirmed by:
• 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,
• Microscopically confirmed parasite infection: 1,000 to 75,000 asexual parasite count/µL blood.
• 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
• Ability to swallow oral medication
• Ability and willingness to participate and access the health facility
• 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.

You may not qualify if:

• Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization Criteria 2010
• Mixed Plasmodium infection
• Presence of other serious or chronic clinical condition requiring hospitalization
• 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)
• 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)
• Known history of hypersensitivity, allergic or adverse reactions to artemisinin containing compounds or mefloquine
• Known active Hepatitis A Immunoglobulin M (IgM) (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab)
• Have received any antimalarial treatment in the preceding 14 days, as determined by history and screening test
• Have received antibacterial with known antimalarial activity in the preceding 14 days
• Have received an investigational drug within the past 4 weeks
• 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
• Hemoglobin (Hb) level =\< 8g/dl
• Total Bilirubin \> 1.5XULN
• Serum creatinine levels more than 2 times the upper limit of normal range (\>2xULN).
• 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.

Sponsors & Collaborators

• Medicines for Malaria Venture: lead

Study Sites (3)

Faculty of Tropical Medicine,

Bangkok, Bangkok, 10400, Thailand

Location

Mae Ramat District hospital

Mae Ramat, Changwat Tak, 63140, Thailand

Location

Shoklo Malaria Research Unit

Mae Sot, Changwat Tak, 63110, Thailand

Location

Related Publications (1)

• Vennerstrom JL, Arbe-Barnes S, Brun R, Charman SA, Chiu FC, Chollet J, Dong Y, Dorn A, Hunziker D, Matile H, McIntosh K, Padmanilayam M, Santo Tomas J, Scheurer C, Scorneaux B, Tang Y, Urwyler H, Wittlin S, Charman WN. Identification of an antimalarial synthetic trioxolane drug development candidate. Nature. 2004 Aug 19;430(7002):900-4. doi: 10.1038/nature02779.

  PMID: 15318224 BACKGROUND

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Dr. Jörg J. Möhrle
• Organization: Medicines for Malaria Venture

moehrlej@mmv.org

+41 22 555 03 00

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: October 25, 2012
• Study Start: March 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: April 14, 2017
• Results First Posted: February 10, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

TH (3)