A Phase 1b, Single-Center, Randomized, Double-Blind, Placebo-Controlled Proof-of-Concept Study to Evaluate Safety, Tolerability, Pharmacokinetics and Mosquitocidal Activity of Single Oral Doses of Lotilaner in Healthy Participants in Mali.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 75
- 试验地点
- 2
- 主要终点
- Safety and tolerability of Lotilaner
研究概览
简要总结
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.
详细描述
Study Design and Recruitment
There will be 3 staggered cohorts of 25 participants each ( 75 participants in total). In each cohort, participants will be randomized in a 4:1 ratio, with 20 receiving a single dose of lotilaner and 5 receiving placebo. The next cohort will commence dosing only following a favorable interim review of at least 8 days of safety and tolerability of the previous cohort(s). The IMP will be administered on the morning of Day 1, either while fasting or 30 minutes after a high-fat meal.
Participants will return to the clinical unit for follow-up visits according to the schedule of assessments for approximately 6 months.
Blood samples will be collected at regular intervals for safety assessment, PK analyses, and evaluation of mosquitocidal efficacy.
Mosquitocidal efficacy of collected blood samples from trial participants will be evaluated using mosquito membrane feeding assays.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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).
- •Signs and symptoms of uncomplicated or severe malaria. An asymptomatic Plasmodium infection is not exclusionary.
- •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.
- •Current or recent use of any prohibited medications according to the study protocol
- •Pre-planned surgery during the study.
- •Intake of lotilaner in the six months before the study drug administration.
- •Receipt of any investigational product within the past 30 days or five half-lives (whichever is longer) before screening.
- •Use of St. John's wort in the 28 days before study treatment administration and through the duration of the study.
- •Participation or planned participation in an interventional trial with an investigational product before the last required protocol visit.
- •Treatment with systemic ivermectin within four weeks or five half-lives (whichever is longer) before Screening.
- •Any individual who, in the judgment of an Investigator, is likely to be non-compliant during the trial, or is unable to cooperate.
- •Any individual who is an Investigator, research assistant, pharmacist, trial coordinator, or other staff thereof, directly involved in conducting the trial.
研究组 & 干预措施
high dose placebo with a high-fat meal
干预措施: Cohort 3 high dose placebo with a high-fat meal (Other)
Cohort 1
low dose lotilaner with a high-fat meal
干预措施: Cohort 1 low dose lotilaner with a high-fat meal (Drug)
Cohort 2
high dose lotilaner in fasted state
干预措施: Cohort 2 high dose lotilaner in fasted state (Drug)
Cohort 3
high dose lotilaner with high-fat meal
干预措施: Cohort 3 high dose lotilaner with a high-fat meal (Drug)
low dose placebo with high-fat meal
干预措施: Cohort 1 low dose placebo with a high-fat meal (Other)
high dose placebo in fasted state
干预措施: Cohort 2 high dose placebo in fasted state (Other)
结局指标
主要结局
Safety and tolerability of Lotilaner
时间窗: From hour 0 on Day 1 through the end of the study (Day 169)
All-cause mortality, Serious Adverse Events, Other (not including Serious) Adverse Events (frequency threshold:5%)
次要结局
- 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)
- Time to reach maximum concentration (tmax) of Lotilaner in whole blood(At protocol-specified timepoints through the end of pharmacokinetic sampling, an average of 6 months)
- Area under the concentration-time curve (AUC) of Lotilaner in whole blood(At protocol-specified timepoints through the end of pharmacokinetic sampling, an average of 6 months)