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

NCT07758985 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: MMV_Loti_23_01
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malaria

Keywords

food effect; safety; pharmacokinetics; lotilaner; mosquitocidal activity

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of Lotilaner

  All-cause mortality, Serious Adverse Events, Other (not including Serious) Adverse Events (frequency threshold:5%)

  From hour 0 on Day 1 through the end of the study (Day 169)

Secondary Outcomes (7)

• Anopheles gambiae mosquito survivorship (% alive) following membrane feeding on participant blood

  Follow up day 34 (5 days post mosquito feeding, on blood collected from participants at follow up day 29)

• Anopheles gambiae mosquito survivorship (% alive) following membrane feeding on participant blood

  Follow up 1-5 days post mosquito feeding on blood collected from participants between study days 1 to 85, according to the schedule of assessments

• Aedes Aegypti mosquito survivorship (% alive) following membrane feeding on participant blood

  Follow up 1-5 days post mosquito feeding on blood collected from participants between study days 1 to 85, according to the schedule of assessments

• Maximum observed concentration (Cmax) of Lotilaner in whole blood

  At protocol-specified timepoints through the end of pharmacokinetic sampling, an average of 6 months

• Terminal serum half-life (t½) of Lotilaner in whole blood

  At protocol-specified timepoints through the end of pharmacokinetic sampling, an average of 6 months

Study Arms (6)

Cohort 1

EXPERIMENTAL

low dose lotilaner with a high-fat meal

Drug: Cohort 1 low dose lotilaner with a high-fat meal

Cohort 2

EXPERIMENTAL

high dose lotilaner in fasted state

Drug: Cohort 2 high dose lotilaner in fasted state

Cohort 3

EXPERIMENTAL

high dose lotilaner with high-fat meal

Drug: Cohort 3 high dose lotilaner with a high-fat meal

low dose placebo with high-fat meal

PLACEBO COMPARATOR

Other: Cohort 1 low dose placebo with a high-fat meal

high dose placebo in fasted state

PLACEBO COMPARATOR

Other: Cohort 2 high dose placebo in fasted state

high dose placebo with a high-fat meal

PLACEBO COMPARATOR

Other: Cohort 3 high dose placebo with a high-fat meal

Interventions

Cohort 1 low dose lotilaner with a high-fat meal DRUG

Participants will receive a single low dose of lotilaner with a high-fat meal

Cohort 1

Cohort 1 low dose placebo with a high-fat meal OTHER

Participants will receive a single low dose of placebo with a high-fat meal

low dose placebo with high-fat meal

Cohort 2 high dose lotilaner in fasted state DRUG

Participants will receive high dose lotilaner in a fasted state

Cohort 2

Cohort 2 high dose placebo in fasted state OTHER

Participants will receive a single high dose of placebo in a fasted state

high dose placebo in fasted state

Cohort 3 high dose lotilaner with a high-fat meal DRUG

Participants will receive a single high dose of lotilaner after a high-fat meal

Cohort 3

Cohort 3 high dose placebo with a high-fat meal OTHER

Participants with receive a single high dose of placebo with a high-fat meal

high dose placebo with a high-fat meal

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female volunteers aged 18-55 years of age (inclusive) at the time of signing the Informed Consent.
• Total body weight (BW) ≥50 kg, and a body mass index (BMI) of 18-32 kg/m2 (inclusive).
• Residence within the study area.
• Judged healthy based on a comprehensive clinical assessment, including a detailed medical history and full physical examination.
• Axillary temperature \<37.0ºC without history of fever during the previous week.
• Willingness to adhere to the requirement regarding the use of contraception, as per the study protocol
• Willingness and ability to adhere to study requirements and to participate and communicate for the duration of the trial.
• Agreement to provide current contact details

You may not qualify if:

• Evidence of clinically significant, gastrointestinal, cardiac, lung, hepatic, neurologic, psychiatric, rheumatologic, autoimmune, dermatologic, hematological, oncologic, or renal disease by anamnesis, physical examination, and/or laboratory tests.
• Known Central Nervous System disorders or a history of seizures.
• Any surgery that may affect drug bioavailability (excluding appendectomy and cholecystectomy).
• Female who is lactating or pregnant according to the serum pregnancy test at Screening.
• History of significant hypersensitivity to lotilaner (including excipients of the formulations) or any related products.
• History of a severe allergic reaction or anaphylaxis or severe hypersensitivity reactions to any drugs.
• Significant history of drug dependency or alcohol abuse (\>3 units of alcohol per day, intake of excessive alcohol, acute or chronic).
• Participants who are current smokers or have used nicotine-containing products within 90 days prior to study treatment administration.
• 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).
• Known asplenia or functional asplenia.
• Known history or evidence of clinically significant cardiovascular abnormalities
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results.
• Known diabetes or diabetes identified during screening
• 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.
• 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.

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Radboud University Medical Center: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• Malaria Research and Training Center, Bamako, Mali: collaborator

Study Sites (1)

Malaria Research and Training Center

Bamako, Mali

Location

MeSH Terms

Conditions

Malaria

Interventions

lotilaner

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Prof. Alassane Dicko, MD, PhD

  MRTC, Université des Sciences Techniques et Technologies de Bamako, Mali

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Helen Demarest

CONTACT

+41225550300; info@mmv.org

Peya Gaye

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2026
• First Posted: August 11, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: August 11, 2026

Record last verified: 2026-08

Locations

MA (1)