Bioavailability Study of Oral OZ439 Prototype Formulations Administered With Piperaquine Phosphate (PQP)
Condition: Malaria
MeSH terms: Malaria
Intervention: 800mg OZ439 prototype formulation 1; 800mg OZ439 prototype formulation 2; 800mg OZ439 prototype formulation 3; 960mg PQP
Intervention MeSH terms: Artefenomel
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Malaria; Bio-availability

Summary:

      A single dose study to investigate how different formulations of OZ439 co-administered with
      PQP tablest are processed by the body when taken without food
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy males, or healthy females of non-childbearing potential ie surgically
             sterilised or post-menopausal (amenorrhoea for at least 1 year and confirmed by a
             follicle stimulating hormone result of ≥25 IU/mL

          2. Age 18 to 55 years of age

          3. Body mass index of 18.0 to 30.0 kg/m2 inclusive. Total body weight >50 kg at screening

          4. Willing and able to communicate and participate in the whole study

          5. Must provide written informed consent

          6. Must agree to use an adequate method of contraception

          7. Must have liver function tests and haemoglobin within the laboratory reference range
             at screening and Day -1

          8. Must have heart trace measurements within the defined healthy limits at screening, Day
             -1 and pre-dose

        Exclusion Criteria:

          1. Male subjects who have currently pregnant partners

          2. Evidence or history of clinically significant oncological, pulmonary, chronic
             respiratory, hepatic, cardiovascular, haematological, metabolic, neurological,
             immunological, nephrological, endocrine or psychiatric disease, or current infection

          3. Clinically relevant abnormalities in the heart trace including any degree of heart
             block, including asymptomatic bundle branch block

          4. Family history of sudden death or of congenital prolongation of the QTc interval or
             known congenital prolongation of the QTc interval or any clinical condition known to
             prolong the QTc interval

          5. History of symptomatic cardiac arrhythmias or with clinically relevant bradycardia

          6. Electrolyte disturbances, particularly hypokalemia, hypocalcaemia or hypomagnesaemia.

          7. Any condition that could possibly affect drug absorption, such as gastrectomy or
             diarrhoea

          8. History of post-antibiotic colitis

          9. History of any drug or alcohol abuse in the past 2 years prior to screening

         10. Subjects who have a breath carbon monoxide reading of greater than 10 ppm at screening
             will be excluded. Subjects who are tobacco users (including smokers and users of
             snuff, chewing tobacco and other nicotine or nicotine-containing products) must have
             stopped use within 90 days before screening.

         11. Receipt of an investigational drug or participation in another clinical research study
             within 90 days prior to drug administration.

         12. Subjects who are study site employees, or immediate family members of a study site or
             sponsor employee.

         13. Subjects who have previously been enrolled in this study

         14. Use of ANY prescription or non-prescription medications, vitamins, herbal supplements
             or dietary supplements, including protein supplements, within 14 days prior to the
             first dose of study drug and throughout the study, unless prior approval is granted by
             both the investigator and the sponsor. An exception will be made for intermittent use
             of paracetamol and hormone replacement therapy. Paracetamol at doses of, at most, 2 g
             per day or no more than 3 consecutive days or 6 non consecutive days, are allowed
             until 24 hours before dosing with study drug. Longer exclusion periods apply for:

               1. amiodarone and hydroxychloroquine (210 days)

               2. monoclonal antibodies/ immunoglobulins/ other therapeutic proteins and
                  experimental drugs for which the half-life is not known to the investigator (120
                  days)

               3. experimental drugs for which half-life is known to the investigator (5 half lives
                  plus 14 days)

               4. chloroquine, piperaquine phosphate and flunarizine (100 days)

               5. fluoxetine (75 days)

               6. benzodiazepines (for midazolam, lorazepam and triazolam, the exclusion period is
                  14 days), chlorpromazine, mephenytoin, nortryptyline, phenobarbital, primidone,
                  phenprocoumone and cytochrome P450 3A4 inducers not already mentioned, including
                  but not restricted to, rifampin, carbamazepine, oxcarbazepine, phenytoin and St
                  John's Wort (35 days)

         15. Positive hepatitis B surface antigen, hepatitis C virus antibody or human
             immunodeficiency virus results

         16. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by
             the investigator

         17. Positive urine drug screen result at screening or admission to the clinical unit

         18. History of intolerance or hypersensitivity to piperaquine or any 4-aminoquinolone, or
             ascertained or presumptive hypersensitivity to the active principle and/or formulation
             ingredients; history of anaphylaxis to drugs or allergic reactions in general, that
             the investigator considers may affect the outcome of the study

         19. Serious adverse reaction or serious hypersensitivity to any drug or the formulation
             excipients

         20. Presence or history of allergy requiring treatment; hayfever is allowed unless it is
             active

         21. Donation or loss of >400 mL of blood within 90 days prior to drug administration

         22. Regular alcohol consumption in males >21 units per week and females >14 units per week
             (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)

         23. Subjects who do not have suitable veins for multiple blood samples as assessed by the
             investigator at screening

         24. Failure to satisfy the investigator of fitness to participate for any other reason