A Study to Evaluate Safety and Efficacy of TP-05 in Healthy Participants With Tick Exposure

This is a randomized, double-blind, placebo-controlled study conducted in healthy adult participants prior to anticipated exposure to Lyme Borreliosis. Participants will be randomized to receive either TP05 or placebo according to a predefined dosing schedule. Safety will be evaluated through adverse event monitoring, clinical laboratory assessments, vital signs, and physical examinations. The study will consist of a screening period, a treatment period (up to 24 weeks) and a safety follow up period. Participants will be randomized to receive one of two treatment regimens of TP-05 or placebo. Participants will be followed up for approximately 15 months and evaluated further for tick bites or symptoms of Lyme borreliosis.

• TP-05 (lotilaner) Low Dose (Drug): TP05 administered orally at the protocol-defined preventative dose.
• TP-05 (lotilaner) High Dose (Drug): TP05 administered orally at the protocol-defined preventative dose.
• Placebo (Drug): Matching placebo administered orally according to the same dosing schedule as TP05.

Primary outcomes

• The Incidence of Treatment Emergent Adverse Events From Baseline [From day 1 through the end of study follow-up, an average of 15 months.]: Safety and tolerability will be evaluated by incidence rate of treatment emergent adverse events from baseline.
• Clinically Significant Changes From Baseline Chemistry Laboratory Tests [From day 1 through the end of study follow up, an average of 15 months.]: Number of participants with clinically significant changes in clinical laboratory tests
• Clinically Significant Changes From Baseline Hematology Laboratory Tests [From day 1 through the end of study follow up, an average of 15 months.]: Number of participants with clinically significant changes in clinical laboratory tests.
• Clinically Significant Changes From Baseline Vital Signs [From day 1 through the end of study follow up, an average of 15 months.]: Number of participants with clinically significant changes in vital signs.
• Clinically Significant Changes From Baseline Electrocardiograms (ECGs) [From day 1 through the end of study follow up, an average of 15 months.]: Safety will be assessed by evaluating clinically significant changes from Baseline ECGs change in mean ventricular rate \[beats/min\].
• Clinically Significant Changes From Baseline Electrocardiograms (ECGs) Measures [From day 1 through the end of study follow up, an average of 15 months.]: Safety will be assessed by evaluating clinically significant changes from Baseline ECGs change in pulse rate \[msec\].
• Clinically Significant Changes From Baseline QTC Interval [From day 1 through the end of study follow up, an average of 15 months.]: Safety will be assessed by evaluating clinically significant changes from Baseline ECGs change in QTC interval
• Clinically Significant Changes From Baseline QRS Interval [From day 1 through the end of study follow up, an average of 15 months.]: Safety will be assessed by evaluating clinically significant changes from Baseline ECGs change in QRS interval.

Secondary outcomes

• Concentration of Lotilaner in Whole Blood [From dose through study completion, an average of 15 months.]: Concentration of lotilaner in whole blood at specified timepoints measured using validated bioanalytical assays.
• Terminal Elimination Half Life (t½) of Lotilaner [At protocol specified timepoints through end study treatment phase, an average of 28 weeks.]: Terminal elimination half life (t½) of lotilaner.
• Area Under the Concentration Time Curve (AUC) of Lotilaner [At protocol specified timepoints through end of pharmacokinetic sampling, an average of 15 months.]: Area under the concentration time curve (AUC) of lotilaner.
• Maximum Observed Concentration (Cmax) of Lotilaner [At protocol specified timepoints through end of pharmacokinetic sampling, an average of 15 months.]: Maximum observed concentration (Cmax) of lotilaner.
• Time to Maximum Observed Concentration (Tmax) of Lotilaner [At protocol specified timepoints through end of pharmacokinetic sampling, an average of 15 months.]: Time to maximum observed concentration (Tmax) of lotilaner.

Sex: All, ages: 18 Years to 70 Years, accepts healthy volunteers

Inclusion Criteria:

* Overtly healthy adult participants aged 18 to 70 years
* Able to provide written informed consent
* Willing and able to comply with study procedures
* At high risk of exposure to ticks
* Contraceptive use by men and women consistent with local regulations

Exclusion Criteria:

* Prior exposure to TP05 or any isooxazoline in the last 12 months
* Known hypersensitivity to TP05 or related compounds
* Clinically significant medical conditions that may interfere with study participation
* Use of investigational products within 30 days prior to screening.
* Received previous vaccination against Lyme borreliosis, including investigational vaccines intended to prevent Lyme borreliosis
* Receiving long-term antibiotic therapy
* Received active or passive immunization within 4 weeks prior to Day
* Pregnant or breastfeeding individuals