A Pharmacokinetic Study of TP-05 in Healthy Subjects
- Conditions
- Healthy
- Interventions
- Drug: PlaceboDrug: TP-05 (lotilaner oral capsules)
- Registration Number
- NCT05138796
- Lead Sponsor
- Tarsus Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 67
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Placebo MAD Placebo Four doses of Placebo TP-05 SAD TP-05 (lotilaner oral capsules) Single dose of TP-05 (lotilaner oral capsules) at 4 dose levels in ascending order Placebo SAD Placebo Single dose of Placebo TP-05 MAD TP-05 (lotilaner oral capsules) Four doses of TP-05 (lotilaner oral capsules) at 3 dose levels in ascending order TP-05 Fasted TP-05 (lotilaner oral capsules) Single dose of TP-05 (lotilaner oral capsules) in a fasted state Placebo Fasted Placebo Single dose of placebo in a fasted state
- Primary Outcome Measures
Name Time Method Incidence of treatment emergent adverse events (TEAEs) up to 151 days Evaluate the safety of TP-05 through the incidence rate of TEAEs
Clinically significant changes from Baseline chemistry laboratory tests 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 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 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 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) 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 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 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 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 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) 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 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 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]) 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]) 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]) 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]) 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) 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 Outcome Measures
Name Time Method Impact of fasting on the PK of lotilaner up to 151 days PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include Ctrough at various times
Exposure and PK of lotilaner in whole blood up to 151 days PK parameters for whole blood sampling methods following dose administration will be evaluated and include Ctrough at various times
Urine exposure and renal PK of lotilaner 3 days PK parameters for urine sampling methods will be evaluated and include CLr0-48.
Trial Locations
- Locations (1)
Altasciences
🇺🇸Overland Park, Kansas, United States