A Exploratory, Open Label, Single Dose Regimen, Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and Pharmacokinetics of OZ439 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection

This study has been completed.
Sponsor:
Collaborator:
Mahidol University
Information provided by (Responsible Party):
Medicines for Malaria Venture
ClinicalTrials.gov Identifier:
NCT01213966
First received: October 1, 2010
Last updated: August 6, 2012
Last verified: August 2012

October 1, 2010
August 6, 2012
October 2010
May 2012   (final data collection date for primary outcome measure)
Derived parasite reduction rate (PRR) at 24 hours [ Time Frame: 24 h after study drug adminstration ] [ Designated as safety issue: No ]
• Parasite reduction ratio at 24 hours after study drug administration estimated separately for each patient from a regression model.The relationship between parasite counts and time will be analysed by fitting a variable lag phase then a linear decline to the Natural log of parasite count versus time relationship. The slope of this log linear relationship is the primary end-point, and all secondary variables related to parasite reduction will be derived from this best fit.
Same as current
Complete list of historical versions of study NCT01213966 on ClinicalTrials.gov Archive Site
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A Exploratory, Open Label, Single Dose Regimen, Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and Pharmacokinetics of OZ439 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection
A Phase IIa Exploratory, Open Label, Single Dose Regimen, Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and Pharmacokinetics of OZ439 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection

A Phase IIa Exploratory, Open label, Single Dose Regimen, Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and Pharmacokinetics of OZ439 in adult patients with acute, uncomplicated Plasmodium falciparum or vivax malaria mono-infection.

This exploratory Phase IIa study aims to investigate the preliminary efficacy in terms of parasite reduction and clearance in malaria patients, and the tolerability of OZ439 administered as single dose regimen at 3 different doses in parallel cohorts of patients with either acute uncomplicated Plasmodium falciparum or Plasmodium vivax malaria mono-infection (10 patients per plasmodium species per dose level). Treatment with OZ439 will be given as a single dose on Day 0, starting in the first cohort at a dose of 800 mg. Established antimalarial therapy will be given at the latest at 36 hours post dosing. Established antimalarial therapy will be given earlier if a patient meets early treatment failure (ETF) defined as: 1) parasitaemia by 12 hours greater or equal to that at pre-dosing, regardless of temperature or 2) parasitaemia at 24 hours which has not fallen by >75% as compared to pre-dose regardless of temperature.

The primary endpoint will be the parasite reduction rate (PRR) slope. This is the slope of the log-linear portion of the loge parasitaemia versus time relationship. From this all other measures such as parasite reduction ratios will be derived (H24). Times to 50% and 90% reduction in parasitaemia will be derived from the best fit relationships.

A review of each individual study cohort (dose/species) will be conducted with the Principal Investigator and the Sponsor and a decision reached on whether the dose for the next cohort should increase or decrease (within 200mg-1600mg range). This decision will be based on parasite reduction rate over the first 24 hours following administration of OZ439, tolerability and exposure. If available data from the parallel cohort, discussion on how to progress will include both cohort findings and decision may include stopping with dose (de) escalation with one cohort and continuing with the other. The predominant consideration on dosing decisions will be that of patient safety.

Based on parasite reduction, the provision of established antimalarial therapy may be delayed beyond 36 hours and up to a maximum of 72 hours from the study drug dose, under continued 6 hourly (4 hourly up to 24 hours) monitoring parasitaemia. This will occur if the patient has achieved a symptomatic recovery but parasitaemia is still detectable at 36 hours.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Plasmodium Falciparum,
  • Plasmodium Vivax
  • Uncomplicated Malaria
Drug: OZ439
po, single dose
  • Experimental: 800 mg OZ439 single dose
    Intervention: Drug: OZ439
  • Experimental: 400 mg OZ439 p.o.
    Intervention: Drug: OZ439
  • Experimental: 200mg OZ439 p.o.
    Intervention: Drug: OZ439
  • Experimental: 1200 mg OZ439 po
    Intervention: Drug: OZ439
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
80
May 2012
May 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Male or female patients between the age of 18 and 60 years, inclusive
  2. Body weight between 40 kg and 90 kg inclusive
  3. Presence of mono-infection of P. falciparum or P. vivax 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, 5,000 to 50,000 asexual parasite count/µl of 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 minimum of 4 days hospitalisation for drug administration and pharmacokinetic sampling

Exclusion Criteria:

  1. Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organisation Criteria 2010 (Attachment 2)
  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 hospitalisation.
  5. Severe malnutrition (defined as the weight-for-height being below -3 standard deviation or less than 70% of median of the NCHS/WHO normalised 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 or drug in the national guidelines for P. vivax.
  8. Known active Hepatitis A 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 (ASAT/ALAT levels) more than 2 x ULN
  13. Hb level below 10 g/dL.
  14. Bilirubin levels greater than 40 µmol/L.
  15. Serum creatinine levels more than 2 times the upper limit of normal range in absence of dehydration. In case of important dehydration the creatinine should be lower than 2X ULN after oral/parenteral rehydration.
  16. Female patients must be neither pregnant (as demonstrated by a negative serum pregnancy test) nor lactating, and must be willing to take measures not to become pregnant during the study period and safety follow-up period
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT01213966
MMV_OZ439_10_002
Yes
Medicines for Malaria Venture
Medicines for Malaria Venture
Mahidol University
Principal Investigator: Sasithon Pukrittayakamee, MD Mahidol University
Medicines for Malaria Venture
August 2012

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