Phase I Study of Ascending Doses of MMV390048 in Healthy Adult Volunteers
Condition: Malaria
MeSH terms: Malaria
Intervention: MMV390048 5mg; MMV390048 20mg; MMV390048 40mg; MMV390048 80mg; MMV390048 120mg; Placebo to match MMV390048
Intervention description: Supplied as "powder in bottle" formulation for reconstitution pre-dose; Supplied as "powder in bottle" formulation for reconstitution pre-dose.; Supplied as "powder in bottle" formulation for reconstitution pre-dose; Supplied as "powder in bottle" formulation for reconstitution pre-dose; Supplied as "powder in bottle" formulation for reconstitution pre-dose; Supplied as "powder in bottle" formulation for reconstitution pre-dose
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: safety; tolerability; malaria

Summary:

      This is a first-in-human study of MMV390048. The study will evaluate the safety, tolerability
      and pharmacokinetic properties of escalating single and multiple doses of MMV390048 when
      administered to healthy male volunteers and female volunteers of non-childbearing potential.

      In addition, the effect of food on the pharmacokinetics and tolerability of MMV390048 will be
      investigated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  written informed consent

          -  Male and female (of non-childbearing potential); age 18 to 55 years, in good health as
             determined by past medical history, physical examination, vital signs,
             electrocardiogram, and laboratory tests at screening

          -  Hematology, clinical chemistry and urinalysis results at screening that are within the
             local laboratory reference range or, if outside the range, not clinically significant.
             AST, ALT, lactate dehydrogenase, total bilirubin, haptoglobin and hemoglobin must be
             within the normal reference ranges

          -  Body weight at least 50kg and body mass index within 18 to 32kg/m2

          -  Good peripheral venous access

          -  Able to communicate well with the investigator, to understand and comply with the
             requirements of the study

          -  Agree to stay in contact with the study site for the duration of the study, provide
             updated contact information as necessary, and have no current plans to move away from
             the study area for the duration of the study

        Exclusion Criteria:

          -  Any acute illness upon admission to the unit on Day -1 or prior to dosing on Day 1

          -  Use of any other investigational drug within 30 days or five half-lives (whichever is
             longer) prior to the first dose of MMV390048

          -  history of hypersensitivity to any drugs

          -  history of anaphylaxis or severe allergic reaction

          -  Resting vital signs at either screening or baseline outside the defined ranges

          -  Orthostatic changes in blood pressure and heart rate measurements greater than: 20
             mmHg drop in systolic blood pressure; 10 mmHg drop in diastolic blood pressure; 20
             beats per minute increase in heart rate

          -  history of clinically significant ECG abnormalities, or any of the defined ECG
             abnormalities at either screening or baseline

          -  History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin), treated or untreated, within the past five years, regardless of whether
             there is evidence of local recurrence or metastases

          -  Pregnant or nursing (lactating) women

          -  Women of child-bearing potential

          -  males physiologically capable of conceiving offspring UNLESS the volunteer agrees to
             use condoms and ensure that his partner(s) is either not of child-bearing potential or
             uses a highly effective method of contraception for the entire duration of the study
             and for twelve weeks following the last study drug administration

          -  Smokers (use of tobacco products in the previous three months)

          -  Use of any prescription drugs, herbal supplements, over--the--counter medication or
             dietary supplements (vitamins included) within four weeks prior to initial dosing

          -  Intake of grapefruit, grapefruit juice or other products containing grapefruit within
             28 days of the first drug administration of the study drug

          -  Excessive intake of caffeine drinks or energy drinks within 48 hours before admission
             defined as more than three 250 ml cups of coffee a day

          -  Donation or loss of 400 ml or more of blood within eight weeks prior to screening or
             initial dosing

          -  Plasma donation (>100 ml) within 60 days prior to first dosing

          -  Hemoglobin levels below 12.5 g/dl (males) or 11.5 g/dl (females) at screening

          -  Haptoglobin levels outside the reference range

          -  Positive direct anti-globulin test

          -  Liver enzymes other than ALT, AST and lactate dehydrogenase elevated ≥1.5 x ULN within
             two weeks prior to initial dosing

          -  history of autonomic dysfunction within 3 years and/or recurrent history

          -  History of immunodeficiency diseases, including a confirmed positive HIV test result

          -  Positive Hepatitis B surface antigen or Hepatitis C antibody test result

          -  History of recurrent infection

          -  history of endocrine disease, in particular adrenal disorders such as Cushing's
             syndrome or Addison's disease, or diabetes mellitus

          -  history of Gilbert's Syndrome

          -  history of photosensitivity

          -  history of any food allergy

          -  Any surgical or medical condition which might significantly alter the absorption,
             distribution, metabolism, or excretion of drugs, or which may jeopardise the safety of
             the volunteer or the objectives of the study

          -  History or presence of impaired renal function as indicated by clinically
             significantly abnormal creatinine or urea values, or abnormal urinary constituents

          -  History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of
             such abuse as indicated by the tests and laboratory assays at screening and/or
             baseline

          -  Any clinically significant mental disorder that could limit the validity of informed
             consent or the volunteer's ability to comply with protocol requirements