A Comparison of the Bioavailability of OZ439 When Delivered Directly to the Small Intestine, or Via the Oral Route
Condition: Healthy Volunteers
Intervention: OZ439 120mg PIB; 120 mg OZ439 caplet; 120mg OZ439 caplet via Enterion capsule
Intervention description: 120mg dose (as free base) of OZ439 as a solution made up from powder in bottle (PIB); 120 mg (as free base) of OZ439 immediate-release (IR) caplet formulation containing nanoparticulate, administered directly via the oral route; 120 mg OZ439 (as free base) in an immediate release (IR) caplet formulation containing nanoparticulate,administered orally via the Enterion capsule and delivered directly to the proximal small bowel (PSB)
Intervention MeSH terms: Artefenomel
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bioavailability

Summary:

      The purpose of this study is to determine the bioavailability of nanoparticulate OZ439
      delivered to the proximal small bowel (PSB) via the Enterion™ capsule relative to oral OZ439
      suspension (current "powder in bottle" [PIB]) and oral nanoparticulate OZ439.

      The study will also characterise the plasma concentration time profile of OZ439 when
      delivered via Enterion capsule to the PSB in comparison with OZ439 PIB formulation delivered
      orally and nanoparticulate OZ439 delivered orally Safety and tolerability of OZ439
      formulations will be determined following delivery to the PSB and administered orally
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy males, or females of non-childbearing potential ie surgically sterilised or
             post-menopausal

          2. Age 18 to 55 years

          3. Body mass index of 18 to 30 kg/m2 inclusive

          4. Total body weight >50 kg

          5. Healthy as determined by pre-study medical history, physical examination (including
             body temperature) and 12-lead ECG

          6. Must have haematology, clinical chemistry and urinalysis results at screening that are
             within the reference range or ncs

          7. Must agree to use an adequate method of contraception

          8. Must demonstrate their ability to swallow an empty size 000 capsule

          9. Must be willing and able to communicate and participate in the whole study

         10. Must provide written informed consent

        Exclusion Criteria:

          1. Evidence or history of clinically significant oncological, pulmonary, chronic
             respiratory, hepatic, cardiovascular, haematological, metabolic, neurological,
             immunological, nephrological, endocrine or psychiatric disease, or current infection

          2. Clinically relevant abnormalities in the ECG (12 standard leads) and/or QTcF >450 ms
             (males) or >470 ms (females)

          3. Evidence or history of clinically significant GI disease or surgery (excluding
             appendectomy or cholecystectomy)

          4. Any condition that could possibly affect drug absorption, eg gastrectomy or diarrhoea

          5. History of post-antibiotic colitis

          6. History of any drug or alcohol abuse in the past 2 years prior to screening

          7. Subjects who have a breath carbon monoxide reading of greater than 10 ppm at
             screening. 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

          8. Receipt of an investigational drug or participation in another clinical research study
             within the previous 3 months

          9. Subjects who are study site employees, or immediate family members of a study site or
             sponsor employee

         10. Subjects who have previously been enrolled in this study

         11. Use of any prescription or non-prescription medications, vitamins, herbal supplements
             or dietary supplements within 14 days prior to the first dose

         12. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab)or
             human immunodeficiency virus (HIV-1 or HIV-2 antibody) results

         13. Positive urine drug screen result

         14. History of intolerance or hypersensitivity to artemisinins

         15. Serious adverse reaction or serious hypersensitivity to any drug or the formulation
             excipients

         16. Presence or history of allergy requiring treatment; hayfever is allowed unless it is
             active

         17. Donation or loss of >400 mL of blood within the previous 3 months

         18. Haemoglobin result below the lower limit of the reference range

         19. Regular alcohol consumption in males >21 units per week and females >14 units per week

         20. Subjects who do not have suitable veins

         21. Acute diarrhoea or constipation in the 7 days before the predicted first study day.

         22. Presence of non-removable metal objects in the abdomen

         23. Radiation exposure exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years

         24. Failure to satisfy the investigator of fitness to participate for any other reason