Malaria: Relative Bioavailability and Food Effect of DSM265
Condition: Healthy Volunteers
Intervention: DSM265-TPGS 34% SDD, 400 mg fasted; DSM265-TPGS 34% SDD, 400 mg fed; DSM265 25% SDD, 400 mg fasted
Intervention description: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fasted state.; New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fed state.; Reference formulation used in early clinical trials.
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase 1, single-dose, open-label, randomized, parallel group design in healthy adults (males, females of non child bearing potential) in 3 groups of 14 subjects each.
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Phase 1 study designed to evaluate the relative bioavailability of a single dose of a test
      formulation, DSM265-TPGS 34% SDD powder in comparison with a reference DSM265 25% SDD powder
      formulation used in early clinical trials.
    

Eligibility criteria:

        1. Subjects or their legally authorized representative must voluntarily sign and date
             each informed consent, approved by an Independent Ethics Committee(IEC) /
             Institutional Review Board (IRB), prior to the initiation of any screening or
             study-specific procedures.

          2. Male or female between 18 and 55 years of age inclusive at the time of screening.

          3. Body Mass Index (BMI) is ≥ 18.0 to ≤ 29.9 kg/m2 after rounding to the tenths decimal.
             BMI is calculated as weight in kg divided by the square of height measured in meters.

          4. Females must be of Non-Childbearing Potential as defined below

             Females do not need to use birth control during or following study drug treatment if
             considered of non-childbearing potential due to meeting any of the following criteria:

               -  Postmenopausal, age ≤ 55 years with no menses for 12 or more months without an
                  alternative medical cause AND an follicle stimulating hormone (FSH) level > 40
                  IU/L.

               -  Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy,
                  or hysterectomy).

          5. Female who is not pregnant, breastfeeding, or considering becoming pregnant during the
             study or for approximately 120 days after the last dose of study drug.

          6. Male subjects who are sexually active with a female partner of childbearing potential,
             must agree to use condoms, even if the male subject has undergone a successful
             vasectomy, from Study Day 1 through 120 days after the last dose of study drug. His
             female partner(s) must also use at least one of the following methods of birth
             control:

               -  Combined (oestrogen and progestogen containing) hormonal birth control (oral,
                  intravaginal, injectable, transdermal) associated with inhibition of ovulation
                  initiated at least 30 days prior to study Baseline Day 1.

               -  Progestogen-only hormonal birth control (oral, injectable, implantable)
                  associated with inhibition of ovulation initiated at least 30 days prior to study
                  Baseline Day 1.

               -  Bilateral tubal occlusion/ligation.

               -  Intrauterine device (IUD).

               -  Intrauterine hormone-releasing system (IUS).

          7. Male who is not considering fathering a child or donating sperm during the study or
             for approximately 120 days after the last dose of study drug.

          8. Laboratory values meet the following criteria:

               -  Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ the upper
                  limit of normal (ULN) at the Screening Visit and upon initial confinement.

               -  Negative test result for hepatitis A virus immunoglobulin M (HAV-IgM), hepatitis
                  B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (Ab) and human
                  immunodeficiency virus (HIV) at screening visit.

               -  Negative screen for drugs of abuse, alcohol or cotinine at screening and upon
                  initial confinement.

               -  For non-postmenopausal female subjects, a negative urine pregnancy test at the
                  screening visit and a negative serum pregnancy test upon initial confinement and
                  prior to the first dose of study drug.

               -  No other laboratory results that the investigator determines are clinically
                  significant.

               -  Platelets greater than or equal to the lower limit of normal.

          9. No clinically significant ECG abnormalities including

               -  No evidence of 2nd or 3rd degree AV block at screening visit and upon initial
                  confinement.

               -  QT interval corrected for heart rate (QTc) using Fridericia's correction formula
                  (QTcF) is ≤ 430 msec (males) or ≤ 450 msec (females) at screening visit and upon
                  initial confinement.

         10. A condition of general good health, based upon the results of a medical history,
             physical examination, vital signs, laboratory profile and a 12-lead ECG.

         11. No history of: epilepsy, any clinically significant cardiac, respiratory (except mild
             asthma as a child), renal, hepatic, gastrointestinal, hematologic or psychiatric
             disease or disorder, or any uncontrolled medical illness.

         12. No history of any clinically significant sensitivity or allergy to any medication or
             food.

         13. No history of or active medical condition(s) or surgical procedure(s) that might
             affect gastrointestinal motility, pH, or absorption [e.g., Crohn's disease, celiac
             disease, gastroparesis, short bowel syndrome, gastric surgery (except pyloromyotomy
             for pyloric stenosis during infancy), cholecystectomy, vagotomy, bowel resection].

         14. No evidence of dysplasia or history of malignancy (including lymphoma and leukemia)
             other than successfully treated non-metastatic cutaneous squamous cell, basal cell
             carcinoma or localized carcinoma in situ of the cervix.

         15. No history of any clinically significant illness/infection/major febrile illness,
             hospitalization, or any surgical procedure within 30 days prior to the first dose of
             study drug.

         16. Has not donated blood (including plasmapheresis), lost ≥ 550 mL blood volume, or
             received a transfusion of any blood product within 8 weeks prior to study drug
             administration.

         17. No consumption of alcohol, grapefruit products, Seville oranges, starfruit products or
             quinine/tonic water within the 72-hour period prior to study drug administration.

         18. No use of tobacco or nicotine-containing products within 180 days prior to the first
             dose of study drug.

         19. No history of clinically significant (per Investigator's judgment) drug or alcohol
             abuse within the last 6 months.

         20. Is not currently enrolled in another interventional clinical study.

         21. Has not been previously enrolled in this study.

         22. In the opinion of the investigator, this subject is a suitable candidate for
             enrollment in the study.

         23. Subjects must not have been treated with any investigational drug within 30 days or 5
             half-lives of the drug (whichever is longer) prior to the first dose of study drug.

         24. Subject must not have received any live vaccine within 4 weeks prior to the first dose
             of study drug, or expected need of live vaccination during study participation
             including at least 4 weeks after the last dose of study drug.

         25. Subject must not require any over-the-counter and/or prescription medication, vitamins
             and/or herbal supplements, with the exception of contraceptives or hormonal
             replacement therapies for females, on a regular basis.

         26. Subject must not use any medications within the 2-week period prior to study drug
             administration.

         27. Receipt of any drug by injection within 30 days or within a period defined by 5
             half-lives, whichever is longer, prior to study drug administration.

         28. No use of known inhibitors (e.g., ketoconazole) or inducers (e.g., carbamazepine) of
             cytochrome P450 3A (CYP3A) within 1 month prior to study drug administration.

         29. No exposure to DSM265 within the past 90 days prior to first dose of study drug.