A Study to Evaluate the Pharmacokinetics of Oral Formulations of MMV390048 Administered Fasted to Healthy Volunteers
Condition: Malaria
MeSH terms: Malaria
Intervention: MMV390048 formulation A; MMV390048 formulation B
Intervention description: MMV390048 formulation A, tablet; MMV390048 formulation B, tablet
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study will be conducted in a single centre, as an open single dose two parallel cohorts
      design with oral doses of MMV390048 administered in healthy male and female subjects between
      18 to 55 years of age. Subjects will be screened within 28 days prior to entering the study.
      On Day 1 of the study each subject will receive one of the two MMV390048 prototype
      formulations, at a dose of 40 mg with 240 mL of water. Subjects will be discharged on Day 3
      after 48h post-dose and they will attend the unit for follow-up visits on Days 5, 7, 10, 14,
      19, 26 and 29.
    

Eligibility criteria:

        Inclusion Criteria:

          -  healthy male or female (non-childbearing potential) of any race, aged 18 to 55 years

          -  body weight at least 50kg and a body mass index 18 to 30Kg/m2

          -  Females must be of non-childbearing potential:

               -  Natural (spontaneous) post-menopausal defined (amenorrheic for at least 12 months
                  without an alternative medical cause with a screening follicle stimulating
                  hormone level >25IU/L (for post-menopause).

               -  Premenopausal with irreversible surgical sterilization by hysterectomy

               -  and/or bilateral oophorectomy or salpingectomy at least 6 months before screening

          -  Males agree to use acceptable methods of contraception if the male subject's partner
             could become pregnant from the time of study medication until 120 days after
             administration of study medication. One of the following acceptable methods of
             contraception must be used:

               -  Condom and occlusive cap (diaphragm or cervical/vault cap) with spermicidal
                  foam/gel/film/cream/suppository

               -  Surgical sterilization (vasectomy with documentation of azoospermia) and an
                  acceptable barrier method (condom or occlusive cap [diaphragm or cervical/vault
                  cap] used with spermicidal foam/gel/film/cream/suppository)

               -  subject's female partner uses oral contraceptives (combination estrogen /
                  progesterone pills), injectable progesterone or sub-dermal implants and an
                  acceptable barrier method

               -  subject's female partner uses medically prescribed topically applied transdermal
                  contraceptive patch and an acceptable barrier method

               -  subject's female partner has undergone documented tubal ligation (female
                  sterilization). In addition, an acceptable barrier method must be used.

               -  subject's female partner has undergone documented placement of an intrauterine
                  device or intrauterine system. In addition, an acceptable barrier method must be
                  used.

               -  True abstinence: when in line with the preferred and usual lifestyle of the
                  subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal,
                  post-ovulation methods) and withdrawal are not acceptable methods of
                  contraception. Abstinent subjects have to agree to use 1 of the above-mentioned
                  contraceptive methods, if they start sexual relationships during the study and
                  for up to 120 days post-study drug

          -  non-smokers or ex-smokers for more than 90 days prior to screening or smoke no more
             than 5 cigarettes per day. If users of nicotine products (spray, patch, e-cigarette,
             etc.) they should use the equivalent of no more than 5 cigarettes /day

          -  Subjects should not donate egg or sperm from the time of administration of study
             medication until 120 days post-study drug

          -  capable of fully understanding and complying with the requirements of the study and
             must sign the informed consent form prior to undergoing any study-related procedures

          -  agree to avoid excessive UV radiation exposure (occupational exposure to the sun,
             sunbathing, tanning salon use, phototherapy, etc.) throughout the study.

        Exclusion Criteria:

          -  Male subjects with a female partner(s) who is (are) pregnant or lactating from the
             time of study medication

          -  Women of childbearing potential, defined as all women physiologically capable of
             becoming pregnant, including women whose career, lifestyle, or sexual orientation
             precludes intercourse with a male partner and women whose partners have been
             sterilized by vasectomy or other means

          -  Current or recurrent disease (e.g. cardiovascular, neurological, renal,
             gastrointestinal, oncologic or other conditions) that may affect the action,
             absorption or disposition of the study medication or could affect clinical assessments
             or clinical laboratory evaluations

          -  Current or relevant history of physical or psychiatric illness that may require
             treatment or make the subject unlikely to fully comply with the requirements or
             complete the study, or any condition that presents undue risk from the investigational
             product or study procedures

          -  Any other significant disease or disorder which, in the opinion of the investigator,
             may either put the subject at risk because of the participation in the study, may
             influence the result of the study, or the subject's ability to participate in the
             study

          -  History of photosensitivity

          -  History or clinical evidence of alcohol or substance abuse. Alcohol abuse is defined
             as regular weekly intake of more than 21 units for males and 14 units for females

          -  Any clinically relevant history of intolerance/allergy to milk or dairy products

          -  Use of an investigational product or participation in a clinical study within 90 days
             before study medication

          -  Donation of blood products or of more than 500ml of blood in 90 days prior to study
             medication

          -  Use of any prescription drugs within 14 days or within 5 times the elimination
             half-life (whichever period is longer) prior to study medication

          -  Use moderate or strong inhibitors and/or inducers of CYP450/Transporters within 4
             weeks prior to study drug administration (or 5 half-lives of the compound if longer)

          -  Use of over-the-counter medications or dietary supplements, including vitamins and
             herbal supplements within 7 days of study drug. With the exception of paracetamol
             which may be used incidentally or for short-term treatment at a maximum of 2g/day

          -  Intake of grapefruit, grapefruit juice or other products containing grapefruit within
             28 days prior to study drug

          -  Excessive intake of caffeine drinks or energy drinks within 48 hours before admission
             (more than three 250ml cups of coffee a day, equivalent to roughly 250mg caffeine)

          -  Any clinically significant abnormal laboratory, vital signs or other safety findings
             as determined by medical history, physical examination or other evaluations at
             screening or admission.

          -  Any liver function tests elevated >1.5 times the upper limit of normal, considered by
             the investigator as clinically relevant, at screening or admission

          -  Abnormal serum Hemoglobin, Haptoglobin, Reticulocyte count or Lactate Dehydrogenase at
             screening/admission

          -  abnormal ECG results at screening/admission results considered as clinically
             significant by the investigator

          -  Confirmed positive urine drug screen (amphetamines, benzodiazepines, cocaine,
             cannabinoids, opiates, barbiturates or methadone) or from the alcohol breath test at
             screening/admission.

          -  positive human immunodeficiency virus, hepatitis B surface antigen, anti Hepatitis
             core antibody, or hepatitis C virus antibody at screening

          -  veins unsuitable for intravenous puncture or cannulation on either arm (e.g. veins
             difficult to locate, access or puncture, veins with a tendency to rupture during or
             after puncture) 23. Any conditions which in the opinion of the investigator would make
             the subject unsuitable for enrolment or could interfere with the subjects'
             participation in or completion of the study