Safety, Tolerability, Pharmacokinetics, and Mosquitocidal Activity of Lotilaner in Healthy Participants in Mali.

This is a Phase 1b, single-cente, randomized, double-blind, placebo-controlled proof-of-concept study evaluating the safety, tolerability, pharmacokinetics and mosquitocidal activity of single oral doses of lotilaner in healthy, adult participants living in Mali.

Inclusion Criteria: 1. Male and female volunteers aged 18-55 years of age (inclusive) at the time of signing the Informed Consent. 2. Total body weight (BW) ≥50 kg, and a body mass index (BMI) of 18-32 kg/m2 (inclusive). 3. Residence within the study area. 4. Judged healthy based on a comprehensive clinical assessment, including a detailed medical history and full physical examination. 5. Axillary temperature \3 units of alcohol per day, intake of excessive alcohol, acute or chronic). 9. Participants who are current smokers or have used nicotine-containing products within 90 days prior to study treatment administration. 10. Severe asthma (defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past two years, or that has required the use of oral or parenteral corticosteroids at any time during the past two years). 11. Known asplenia or functional asplenia. 12. Known history or evidence of clinically significant cardiovascular abnormalities 13. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results. 14. Known diabetes or diabetes identified during screening 15. Any serious medical condition or abnormality in clinical laboratory tests that, in the opinion of the investigator, precludes the Participant's safe participation in and completion of the study or affects the ability of the Participant to understand and comply with the study protocol. 16. Prior antimalarial therapy or antibiotics with antimalarial activity (prophylaxis or treatment) within four weeks or five half-lives (whichever is longer) before study drug administration. 17. Current or recent use of any prohibited medications according to the study protocol 18. Pre-planned surgery during the study. 19. Intake of lotilaner in the six months before the study drug administration. 20. Receipt of any investigational product within the past 30 days or five half-lives (whichever is longer) before screening. 21. Use of St. John's wort in the 28 days before study treatment administration and through the duration of the study. 22. Participation or planned participation in an interventional trial with an investigational product before the last required protocol visit. 23. Treatment with systemic ivermectin within four weeks or five half-lives (whichever is longer) before Screening. 24. Any individual who, in the judgment of an Investigator, is likely to be non-compliant during the trial, or is unable to cooperate. 25. Any individual who is an Investigator, research assistant, pharmacist, trial coordinator, or other staff thereof, directly involved in conducting the trial.