Clinical trial: A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetic Profile of a Single Doses of MMV533. (NCT04323306)

Eligibility criteria:
Inclusion Criteria

          1. Males and females (of childbearing and non-childbearing potential) , between 18 and 55
             years of age, inclusive. Women of childbearing potential (WOCBP) must use highly
             effective methods of birth control (see Inclusion #3).

          2. Females of non-childbearing potential:

               1. Natural (spontaneous) post-menopausal defined as being amenorrhoeic for at least
                  12 months without an alternative medical cause with a screening follicle
                  stimulating hormone level (FSH) >25 IU/L (or at the local laboratory levels for
                  post-menopause)

               2. Premenopausal with irreversible surgical sterilization by hysterectomy and/or
                  bilateral oophorectomy or salpingectomy at least 6 months before screening (as
                  determined by participant medical history)

          3. Women of childbearing potential that have or may have male sexual partners during the
             course of the study must agree to the use of a double method of contraception of a
             highly effective method of birth control combined with a barrier contraceptive
             (condom) when appropriate from screening visit to until 60 days after the last dose of
             IMP (covering a full menstrual cycle of 30 days starting after 5 half-lives of last
             dose of IMP. This duration is based on the predicted half-life of IMP, and may be
             amended once the actual half-life is calculated during this study). Note: Highly
             effective birth control methods include: combined (oestrogen and progestogen
             containing) oral/intravaginal/transdermal hormonal contraception associated with
             inhibition of ovulation, progestogen-only oral/injectable/implantable hormonal
             contraception associated with inhibition of ovulation, intrauterine device (IUD),
             intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised
             partner, or sexual abstinence or same sex relationship.

          4. Male participants who have, or may have female sexual partners during the course of
             the study must agree to use a double method of contraception including condom plus
             diaphragm, or condom plus stable insertable (implant or IUD), injectable, transdermal
             or combination oral contraceptive by the female partner, from the time of informed
             consent through to 90 days after the last dose of the IMP (covering a full
             spermatogenesis cycle of 60 days starting after 5 half-lives of last dose of IMP. This
             duration is based on the predicted half-life of IMP, and may be amended once the
             actual half-life is calculated during this study).

             Abstinent male participants must agree to start a double method if they begin a sexual
             relationship with a female during the trial, and through to 90 days after the last
             dose of the IMP. Male participants with female partners that are surgically sterile or
             post-menopausal (defined as being amenorrhoeic for at least 12 months without an
             alternative medical cause), or male participants who have undergone sterilisation and
             have had testing to confirm the success of the sterilisation, may also be included and
             will not be required to use above described methods of contraception. Male
             participants must also agree not to donate sperm up to 3 months after dosing with the
             IMP.

          5. Total body weight greater than or equal to 50 kg, and body mass index (BMI) between 18
             and 32 kg/m2 inclusive.

          6. Certified as healthy by a comprehensive clinical assessment (detailed medical history
             and complete physical examination).

          7. Normal vital signs after 5 minutes resting in supine position:

               -  Systolic blood pressure (SBP) - 90-140 mmHg,

               -  Diastolic blood pressure (DBP) - 40-90 mmHg,

               -  Heart rate (HR) 40-100 bpm.

          8. Standard 12-lead electrocardiogram (ECG) parameters after 10 minutes resting in supine
             position in the following ranges for both males and females: QT ≤ 500 msec, QTcF ≤450
             msec, QTcB ≤450 msec, and PR interval ≤210 msec; and normal ECG tracing unless the
             Principal Investigator or delegate considers an ECG tracing abnormality to be not
             clinically significant.

          9. Having given written informed consent prior to undertaking any study-related
             procedure.

         10. Available for the duration of the study and for 2 weeks following the End of Study
             visit.

         11. In the opinion of the Principal Investigator or delegate, the individual has a high
             probability of adherence with and completion of the study, and willing and able to
             withdraw and refrain from restricted medications.

         12. Fluent in English and able to understand and comply with written and verbal
             protocol-related requirements.

         13. Willing to defer blood donations to a blood service for a minimum of 6 months after
             the End of Study visit.

        Exclusion Criteria

          1. Haematology, biochemistry or urinalysis results that are abnormal/outside of
             laboratory normal reference ranges AND are either:

               -  considered clinically significant by the Principal Investigator or delegate; OR

               -  considered not clinically significant by the Principal Investigator or delegate
                  BUT ARE ALSO outside of the Sponsor-approved clinically acceptable laboratory
                  ranges in Appendix 1 of the protocol.

             NOTE: Participants are not excluded if abnormal/out of laboratory normal reference
             range results are considered not clinically significant by the Principal Investigator
             or delegate AND are within the ranges specified in Appendix 1 of the protocol of .

          2. Positive serum pregnancy test at screening, positive urine pregnancy test upon
             admission or at other timepoints as specified by schedule of assessments.

          3. Male participants with a female partner(s) who is (are) pregnant or lactating from the
             time of the administration of study medication.

          4. Any history or presence of clinically relevant cardiovascular, broncho-pulmonary,
             gastrointestinal, hepatic/ gallbladder*/ bile duct, renal, metabolic, haematological,
             neurological, musculoskeletal/rheumatologic, systemic, ocular, gynaecologic (if
             female), or infectious disease, or signs of acute illness. *including medical history
             of asymptomatic gallbladder stones.

          5. Any gastrointestinal surgery or any condition or disease that could affect drug
             absorption, distribution or excretion (eg, gastrectomy, cholecystectomy, diarrhoea).

          6. Severe recurring headaches (cluster or migrainous headaches) requiring prescription
             medication/s. History of recurrent nausea and/or vomiting (for vomiting only: more
             than twice a month).

          7. Participation in any research study involving blood sampling (more than 450 mL/unit of
             blood) or blood donation during the 8 weeks prior to IMP administration (Parts 1 and
             2).

          8. Any documented evidence of current or past cardiovascular disease including cardiac
             arrhythmias or family history of congenital long QT syndrome, Brugada syndrome, or
             unexplained sudden cardiac death. Symptomatic postural hypotension at screening
             (confirmed on two consecutive readings), irrespective of the decrease in blood
             pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood
             pressure ≥20 mmHg within 2-3 min when changing from supine to standing position.

          9. History or presence of diagnosed (by an allergist/immunologist) or treated (by a
             physician) food or known drug allergies, or any history of anaphylaxis or other severe
             allergic reactions including face, mouth, or throat swelling or any difficulty
             breathing. Participants with seasonal allergies/hay fever or allergy to animals or
             house dust mite that are untreated and asymptomatic at the time of dosing can be
             enrolled in the trial.

         10. History of convulsion (including drug or vaccine-induced episodes). A medical history
             of a single febrile convulsion during childhood is not an exclusion criterion.

         11. History of substance use disorder(s) within 5 years of screening, including alcohol
             consumption of more than 40g/4 units/4 standard drinks per day or any prior
             intravenous use of an illicit substance.

         12. Smoked >1 pack of cigarettes per day for >10 years, or who currently (within 14 days
             prior to IMP administration (Parts 1 and 2) smokes >5 cigarettes per day.

         13. Any medication (including herbal such as St John´s Wort, vitamin supplements and over
             the counter [OTC]) within 5 half-lives prior to IMP administration (Parts 1 and 2),
             except occasional intakes (for acute pain) of ibuprofen at doses up to 1.8g/day,
             paracetamol at doses up to 4g/day, acetylsalicylic acid (300 to 650 mg orally every 4
             to 6 hours as needed Maximum dose: 4g in 24 hours), diclofenac (diclofenac potassium
             liquid-filled capsules: 25mg orally 4 times a day; diclofenac free acid capsules: 18
             or 35 mg orally 3 times a day; diclofenac potassium immediate-release tablets: 50mg
             orally 3 times a day [initial dose of 100mg orally followed by 50mg oral doses
             acceptable if required for better relief]) and contraceptives.

         14. Any individual who, in the judgement of the Principal Investigator or delegate, is
             likely to be noncompliant during the study, or unable to cooperate because of a
             language problem or poor mental development.

         15. Any individual in the exclusion period of a previous study according to applicable
             regulations.

         16. Any individual who cannot be contacted in case of emergency.

         17. Any individual who is the Investigator, or delegates, research assistant, pharmacist,
             study coordinator, project manager, or other staff thereof, directly involved in
             conducting the study.

         18. Any individual without a good peripheral venous access.

         19. Participation in any investigational product study within the 12 weeks preceding IMP
             administration (Parts 1 and 2) or 5 times the half-life of the Investigational
             product, whichever is longer.

         20. Positive serology test for hepatitis B (positive HB sAG or anti-HBc Ab), hepatitis C
             (anti-HCV) or human immune deficiency virus (HIV) (positive for anti-HIV1 and
             anti-HIV2 Ab).

         21. Positive urine drug test at screening or prior to IMP dosing. Any drug from the list
             of drugs tested unless there is an acceptable explanation to the Principal
             Investigator or delegate (eg, participant has stated in advance that they consumed a
             prescription of over the counter product which contained the detected drug) and/or the
             participant has a negative urine drug screen on retest. Any participant tested
             positive for paracetamol at screening may still be eligible for study participation,
             at the Principal Investigator's or delegate's discretion.

         22. Positive alcohol screen at screening or prior to IMP dosing.

         23. Any consumption of citrus fruits (grapefruit, Seville oranges) or their juices within
             5 days prior to IMP administration.

         24. Use of antidepressant medication in the past 12 months prior to IMP administration in
             Part 1 and 2.

         25. Individuals with history of schizophrenia, bipolar disorder psychoses, disorders
             requiring lithium, attempted or planned suicide, or any other severe (disabling)
             chronic psychiatric diagnosis including generalised anxiety and obsessivecompulsive
             disorders.

         26. Individuals who have been hospitalised within five years prior to enrolment for either
             a psychiatric illness or due to danger to self or others.

         27. History of an episode of mild/moderate depression lasting more than 6 months that
             required pharmacological therapy and/or psychotherapy within the last 5 years; or any
             episode of major depression. The Beck Depression Inventory (BDIII) will be used as a
             validated tool for the assessment of depression at screening. In addition to the
             conditions listed above, individuals with a score of 20 or more on the BDI-II and/or a
             response of 1, 2 or 3 for item 9 of this inventory (related to suicidal ideation) will
             not be eligible for participation. These individuals will be referred to a general
             practitioner or medical specialist as appropriate. Individuals with a BDI-II score of
             17 to 19 may be enrolled at the discretion of an Investigator if they do not have a
             history of the psychiatric conditions mentioned in this criterion and their mental
             state is not considered to pose additional risk to the health of the individual or to
             the execution of the trial and interpretation of the data gathered.

         28. History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin or in situ cervical cancer considered treated and cured), treated or
             untreated, within 5 years of screening, regardless of whether there is no evidence of
             local recurrence or metastases.

         29. Any vaccination within 28 days of screening.

         30. Any medical condition that in the opinion of the Principal Investigator or delegate
             would jeopardize the individual's involvement in the study.

             Specific to Part 2 only:

         31. Any individual who, in the opinion of the Principal Investigator or delegate, would be
             unwilling or unable to consume the pre-dose test meal during the fed arm.

         32. Individuals with food intolerance or food allergy are excluded. Vegetarian individuals
             must be excluded, unless they agree to eat a full diet during the study.
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 55 Years

Patient description (medical language): A 19-year-old girl comes to the clinic due to a left wrist mass.  She noticed swelling on the top of her wrist about 4 months ago and came to the clinic due to cosmetic concerns.  Examination shows a nontender, rounded mass on the dorsal wrist that transilluminates with a penlight. Vital signs are normal. The patient needs to type on her computer almost all day. She is left-handed. She does not smoke or use illicit drugs. She is in sexual relationship with two male partners and uses condoms.

Patient description (patient's own words): I'm a 19-year-old girl and I went to see my doctor because of a mass on my left wrist. I noticed a swelling on top of my wrist, like 4 months ago, and I went the first time to the doctor because it was pretty ugly! My wrist was not tender, and the mass was round and let the light go through when the doctor used a penlight. My blood pressure, breathing and temperature were normal. I'm left-handed and I need to be on my PC all day. I don't smoke or do drugs. I'm sexually active and I have 2 male partners but they all use condoms.

Does the patient match the trial criteria? Entailment