A Phase 1, Randomized, Double-Blind, Single- and Multiple-Ascending-Dose Study Evaluating the Safety, Tolerability, Food-Effect and Pharmacokinetics of TP-05 in Healthy Subjects
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Tarsus Pharmaceuticals, Inc.
- Enrollment
- 67
- Locations
- 1
- Primary Endpoint
- Incidence of treatment emergent adverse events (TEAEs)
Study Overview
Brief Summary
A Phase 1, Randomized, Double-Blind, Single- and Multiple-Ascending Dose Study Evaluating the Safety, Tolerability, Food-Effect and Pharmacokinetics of TP-05 in Healthy Subjects
Detailed Description
This Phase 1 study is a randomized, double-blind, single- and multiple-ascending dose trial to evaluate the safety, tolerability, food-effect, and pharmacokinetics of TP-05 in healthy subjects. Subjects will be enrolled in 5 sequential, ascending single dose cohorts and 3 multiple, ascending dose cohorts. Dose escalation will be approved by a safety monitoring committee before beginning the next cohort. The Safety Review Committee (SRC) will evaluate if any dose-limiting adverse events (AEs) through Day 15 (in Cohorts 1-5) or through Day 36 (in Cohorts 6-8) occurred in a cohort before proceeding to dosing in the next dose level. In addition, the SRC will review selected PK parameters after selected cohorts. Skin punch biopsies, and venous, capillary, and urine samples may be collected at various timepoints for pharmacokinetic analysis. Safety assessments include monitoring of adverse events, clinical laboratory testing, vital sign measurements, physical examinations, and ECGs. A blood sample may also be collected to evaluate tick mortality upon exposure.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Basic Science
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Masking Description
The investigators, study coordinators, study subjects, and the sponsor will be blinded to treatment assignment.
Eligibility Criteria
- Ages
- 18 Years to 59 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Provision of signed and dated informed consent form (ICF)
- •Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by an investigator
Exclusion Criteria
- •Female who is pregnant or lactating
- •Presence or history of significant gastrointestinal, metabolic, liver or kidney disease, or surgery that may affect drug bioavailability (excluding appendectomy and cholecystectomy)
- •History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease
- •Have a history of a malignancy (or active malignancy), with the exception of treated basal cell or squamous cell carcinoma
- •Use of any prescription drugs (with the exception of hormonal contraceptives or hormone replacement therapy) within 14 days prior to or use of any over-the-counter drugs in the 7 days prior to the first study drug administration
- •Positive urine alcohol test result and/or drugs of abuse at Screening or prior to the first drug administration (including cotinine, cannabinoids, amphetamines, barbiturates, cocaine, opiates, phencyclidine and benzodiazepines)
- •Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg) or Hepatitis C Antibody (HCVAb)
- •Treatment with an investigational drug within 30 days or 5 times the half-life (whichever is longer) prior to Screening
- •Blood donation (excluding plasma donation) of approximately 500 mL within 56 days prior to Screening
- •Plasma donation within 7 days prior to screening
Arms & Interventions
TP-05 SAD
Single dose of TP-05 (lotilaner oral capsules) at 4 dose levels in ascending order
Intervention: TP-05 (lotilaner oral capsules) (Drug)
Placebo SAD
Single dose of Placebo
Intervention: Placebo (Drug)
TP-05 MAD
Four doses of TP-05 (lotilaner oral capsules) at 3 dose levels in ascending order
Intervention: TP-05 (lotilaner oral capsules) (Drug)
Placebo MAD
Four doses of Placebo
Intervention: Placebo (Drug)
TP-05 Fasted
Single dose of TP-05 (lotilaner oral capsules) in a fasted state
Intervention: TP-05 (lotilaner oral capsules) (Drug)
Placebo Fasted
Single dose of placebo in a fasted state
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Incidence of treatment emergent adverse events (TEAEs)
Time Frame: up to 151 days
Evaluate the safety of TP-05 through the incidence rate of TEAEs
Clinically significant changes from Baseline chemistry laboratory tests
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline chemistry laboratory tests
Clinically significant changes from Baseline hematology laboratory tests
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline hematology laboratory tests
Clinically significant changes from Baseline general appearance
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline general appearance
Clinically significant changes from Baseline physical examination of head, ears, nose, and throat
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examinations of head, ears, nose, and throat
Clinically significant changes from Baseline physical examination of neck (thyroid)
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examinations of neck (thyroid)
Clinically significant changes from Baseline physical examination of respiratory system
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examinations of respiratory system
Clinically significant changes from Baseline physical examination of cardiovascular system
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examinations of cardiovascular system
Clinically significant changes from Baseline physical examination of gastrointestinal system
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examinations of gastrointestinal system
Clinically significant changes from Baseline physical examination of neurological system
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examinations of neurological system
Clinically significant changes from Baseline physical examination of musculoskeletal system (extremities)
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examination of musculoskeletal system (extremities)
Clinically significant changes from Baseline physical examination of skin
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examination of skin
Clinically significant changes from Baseline vital signs
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline vital signs (including temperature \[degrees Celsius\], pulse rate \[beats per minute\], respiration rate \[breaths per minute\], and changes in systolic and diastolic blood pressure \[mmHg\])
Clinically significant changes from Baseline vital signs (temperature [degrees Celsius])
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline vital signs including temperature \[degrees Celsius\]
Clinically significant changes from Baseline vital signs (pulse rate [beats per minute])
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline vital signs including pulse rate \[beats per minute\]
Clinically significant changes from Baseline vital signs (respiration rate [breaths per minute])
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline vital signs including respiration rate \[breaths per minute\]
Clinically significant changes from Baseline vital signs (systolic and diastolic blood pressure [mmHg])
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline vital signs including changes in systolic and diastolic blood pressure \[mmHg\])
Clinically significant changes from Baseline electrocardiograms (ECGs)
Time Frame: up to 151 days
Evaluate the safety of TP-05 through clinically significant changes from Baseline ECGs (including changes in mean ventricular rate \[beats/min\], pulse rate \[msec\], QRS duration \[msec\], QT interval \[msec\], QTcF interval \[msec\])
Secondary Outcomes
- Impact of fasting on the PK of lotilaner(up to 151 days)
- Exposure and PK of lotilaner in whole blood(up to 151 days)
- Urine exposure and renal PK of lotilaner(3 days)