Healthy
Conditions
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.
Interventions
DRUGTP-05 (lotilaner oral capsules)
TP-05 (lotilaner oral capsules)
DRUGPlacebo
Placebo to match TP-05 (lotilaner oral capsules)
Sponsors
Tarsus Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The investigators, study coordinators, study subjects, and the sponsor will be blinded to treatment assignment.
Intervention model description
Part 1: a randomized, double-blind, single ascending dose (SAD) with Cohort 1-4 administered on a full stomach and Cohort 5 administered after a period of fasting Part 2: a randomized, double-blind, multiple ascending dose (MAD) escalation with Cohort 6-8 administered on a full stomach.
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated informed consent form (ICF) 2. 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
1. Female who is pregnant or lactating 2. Presence or history of significant gastrointestinal, metabolic, liver or kidney disease, or surgery that may affect drug bioavailability (excluding appendectomy and cholecystectomy) 3. History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease 4. Have a history of a malignancy (or active malignancy), with the exception of treated basal cell or squamous cell carcinoma 5. 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 6. 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) 7. Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg) or Hepatitis C Antibody (HCVAb) 8. Treatment with an investigational drug within 30 days or 5 times the half-life (whichever is longer) prior to Screening 9. Blood donation (excluding plasma donation) of approximately 500 mL within 56 days prior to Screening 10. Plasma donation within 7 days prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 \[msec\]) |
| 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 \[mmHg\]) |
| 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 \[degrees Celsius\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urine exposure and renal PK of lotilaner | 3 days | PK parameters for urine sampling methods will be evaluated and include Ae. |
| 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 Cmax 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 Cmax at various times |
Countries
United States
Outcome results
None listed