Efficacy, Tolerability, PK of OZ439 in Adults With Acute, Uncomplicated P.Falciparum or Vivax Malaria Mono-infection
Condition: Malaria, Falciparum; Malaria, Vivax
MeSH terms: Malaria; Malaria, Falciparum; Malaria, Vivax
Intervention: OZ439
Intervention description: po, single dose
Intervention MeSH terms: Artefenomel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 82.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Acute uncomplicated Plasmodium Falciparum malaria; Blood stage Plasmodium Vivax malaria

Summary:

      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.
    

Eligibility criteria:

        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