First-in-Human Study to Assess the Safety, Tolerability and Pharmacokinetics of MMV367

• Status: Recruiting
• Trial end date: 2022-12-23
• Target enrollment: 0
• Participant gender: All

Summary

This three-part, first-in-human, healthy volunteer study aims to assess the safety and tolerability of the test medicine as well as how it is taken up by the body when given as single and multiple doses. The effect of food on the test medicine will also be investigated.

In Part 1, up to 40 volunteers will be split into up to 5 groups and will receive single oral doses of the test medicine or dummy medicine (placebo), at different dose levels.

In Part 2, up to 8 volunteers will receive one oral dose of the test medicine in the fed state and one oral dose in the fasted state.

In Part 3, up to 24 volunteers will be split into up to 3 groups and will receive single oral daily doses of the test medicine or placebo for 3 consecutive days.

Volunteers' blood and urine will be taken throughout the study for analysis of the test medicine and for their safety. In Part 1 and Part 3, volunteers will be discharged from the clinical unit 4 days after the final dose of the test medicine and will return to the clinical unit on two occasions for safety assessments to be performed. In Part 2, volunteers will be discharged from the clinical unit 4 days after the final dose of the test medicine and will return to the clinical unit on a single occasion for safety assessments to be performed. Volunteers are expected to be involved in this study for approximately 6 weeks for all study parts, from screening to the final return visit.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Medicines for Malaria Venture
• Collaborators: Banook Group; GlaxoSmithKline; Quotient Sciences; Swiss Bio Quant; The Doctors Laboratory

Criteria

Inclusion Criteria:

1. Must provide written informed consent

2. Must be willing and able to communicate and participate in the whole study Demographics and Contraception

3. Aged 18 to 55 years inclusive at the time of signing informed consent

4. Must agree to adhere to the contraception requirements defined in Section 9.4 Baseline characteristics

5. Healthy males or non-pregnant, non-lactating healthy females.

6. Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening

7. Weight ≥50 kg at screening

Exclusion Criteria:

• Medical/Surgical History and Mental Health

1. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients

2. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active

3. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator

4. Blood pressure (supine) at screening or admission outside the range of 90 to 140 mmHg systolic or 50 to 90 mmHg diastolic; and pulse rate outside the range of 45 to 100 bpm, unless deemed not clinically significant by the investigator

5. A decrease of SBP ≥20 mmHg after 3 min standing and/or a decrease of DBP

≥10 mmHg after 3 min standing, at screening

6. History or presence of known structural cardiac abnormalities, family history of long QT syndrome, cardiac syncope or recurrent, idiopathic syncope, exercise related clinically significant cardiac events. Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG or clinically important abnormalities that may interfere with the interpretation of QT interval changes

7. Presence of sinus node dysfunction, clinically significant PR interval prolongation (>210 msec), intermittent second- or third-degree atrioventricular block, complete bundle branch block, sustained cardiac arrhythmias including (but not limited to) atrial fibrillation or supraventricular tachycardia; any symptomatic arrhythmia with the exception of isolated extra systoles, abnormal T wave morphology which may impact on the QT/QTc assessment, or QTcF >450 msec. Participants with borderline abnormalities may be included if the deviations do not pose a safety risk, and if agreed between the sponsor's medical monitor and the investigator

8. Participants with a history of cholecystectomy or gall stones

9. Participants with conditions that affect their ability to smell or taste (Part 1 only) including, but not limited to mouth ulcers, gum disease, nasal surgery and smell and/or taste disorders (e.g. dysosmia, dysgeusia, respiratory and/or sinus infection or cold) Physical Examination

10. Participants who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening Diagnostic assessments

11. Evidence of current SARS-CoV-2 infection

12. Clinically significant abnormal clinical chemistry, haematology, coagulation or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1 of protocol). Participants with Gilbert's Syndrome are not allowed.

13. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results

14. Females who are pregnant or lactating (all female participants must have a negative highly sensitive serum pregnancy test at screening and a negative urine pregnancy test at admission) Prior Study Participation

15. Participants who have received any IMP in a clinical research study within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer

16. Participants who have previously been administered IMP in this study. Participants who have taken part in Part 1 are not permitted to take part in Parts 2 and 3 and participants who have taken part in Part 2 are not permitted to take part in Part 3

17. Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood Prior and Concomitant Medication

18. Participants who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g of paracetamol per day, hormonal contraception or HRT) in the 14 days before first IMP administration (see Section 11.4)

19. Participants who have received a COVID-19 vaccine within 7 days before first IMP administration Lifestyle Characteristics

20. History of any drug or alcohol abuse in the past 2 years

21. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type)

22. A confirmed positive alcohol breath test at screening or admission

23. Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission

24. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months

25. Confirmed positive drugs of abuse test result (drugs of abuse tests are listed in Appendix 1)

26. Participant with a vegan or vegetarian diet (Part 2 only) Other

27. Male participants with pregnant or lactating partners

28. A score of 20 or more on the Beck Depression Inventory (BDI-II), and/or a response of 1, 2 or 3 for item 9 of this inventory (related to suicidal ideation) [7].

Note, individuals with a BDI-II score of 17-19 may be enrolled, at the discretion of the investigator, if they do not have a medical history of psychiatric conditions 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

29. Participants who are, or are immediate family members of, a study site or sponsor employee

30. Failure to satisfy the investigator of fitness to participate for any other reason