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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TP-05 SAD | Experimental | Single dose of TP-05 (lotilaner oral capsules) at 4 dose levels in ascending order |
|
| Placebo SAD | Experimental | Single dose of Placebo |
|
| TP-05 MAD | Experimental | Four doses of TP-05 (lotilaner oral capsules) at 3 dose levels in ascending order |
|
| Placebo MAD | Experimental | Four doses of Placebo |
|
| TP-05 Fasted | Experimental | Single dose of TP-05 (lotilaner oral capsules) in a fasted state |
|
| Placebo Fasted | Experimental | Single dose of placebo in a fasted state |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TP-05 (lotilaner oral capsules) | Drug | TP-05 (lotilaner oral capsules) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of treatment emergent adverse events (TEAEs) | Evaluate the safety of TP-05 through the incidence rate of TEAEs | up to 151 days |
| Clinically significant changes from Baseline chemistry laboratory tests | Evaluate the safety of TP-05 through clinically significant changes from Baseline chemistry laboratory tests | up to 151 days |
| Clinically significant changes from Baseline hematology laboratory tests | Evaluate the safety of TP-05 through clinically significant changes from Baseline hematology laboratory tests | up to 151 days |
| Clinically significant changes from Baseline general appearance | Evaluate the safety of TP-05 through clinically significant changes from Baseline general appearance | up to 151 days |
| Clinically significant changes from Baseline physical examination of head, ears, nose, and throat | Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examinations of head, ears, nose, and throat | up to 151 days |
| Clinically significant changes from Baseline physical examination of neck (thyroid) | Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examinations of neck (thyroid) | up to 151 days |
| Clinically significant changes from Baseline physical examination of respiratory system |
| Measure | Description | Time Frame |
|---|---|---|
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include Cmax at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeremy Lim | Tarsus Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Altasciences | Overland Park | Kansas | 66212 | United States |
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| ID | Term |
|---|---|
| C000711088 | lotilaner |
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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.
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The investigators, study coordinators, study subjects, and the sponsor will be blinded to treatment assignment.
| Placebo | Drug | Placebo to match TP-05 (lotilaner oral capsules) |
|
Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examinations of respiratory system |
| up to 151 days |
| Clinically significant changes from Baseline physical examination of cardiovascular system | Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examinations of cardiovascular system | up to 151 days |
| Clinically significant changes from Baseline physical examination of gastrointestinal system | Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examinations of gastrointestinal system | up to 151 days |
| Clinically significant changes from Baseline physical examination of neurological system | Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examinations of neurological system | up to 151 days |
| Clinically significant changes from Baseline physical examination of musculoskeletal system (extremities) | Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examination of musculoskeletal system (extremities) | up to 151 days |
| Clinically significant changes from Baseline physical examination of skin | Evaluate the safety of TP-05 through clinically significant changes from Baseline physical examination of skin | up to 151 days |
| Clinically significant changes from Baseline vital signs | 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]) | up to 151 days |
| Clinically significant changes from Baseline vital signs (temperature [degrees Celsius]) | Evaluate the safety of TP-05 through clinically significant changes from Baseline vital signs including temperature [degrees Celsius] | up to 151 days |
| Clinically significant changes from Baseline vital signs (pulse rate [beats per minute]) | Evaluate the safety of TP-05 through clinically significant changes from Baseline vital signs including pulse rate [beats per minute] | up to 151 days |
| Clinically significant changes from Baseline vital signs (respiration rate [breaths per minute]) | Evaluate the safety of TP-05 through clinically significant changes from Baseline vital signs including respiration rate [breaths per minute] | up to 151 days |
| Clinically significant changes from Baseline vital signs (systolic and diastolic blood pressure [mmHg]) | Evaluate the safety of TP-05 through clinically significant changes from Baseline vital signs including changes in systolic and diastolic blood pressure [mmHg]) | up to 151 days |
| Clinically significant changes from Baseline electrocardiograms (ECGs) | 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]) | up to 151 days |
PK parameters for whole blood sampling methods following dose administration will be evaluated and include Tmax at various times
| up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include Tlag at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include AUC0-168 at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include AUC0-2880 at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include AUC0-t at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include AUC0-inf at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include CL/F at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include Vz/F at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include eff at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include Thalf at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include λz at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include AUC%extrap at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include MRT0-t at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include Rac at various times | up to 151 days |
| Exposure and PK of lotilaner in whole blood | PK parameters for whole blood sampling methods following dose administration will be evaluated and include Ctrough at various times | up to 151 days |
| Urine exposure and renal PK of lotilaner | PK parameters for urine sampling methods will be evaluated and include Ae. | 3 days |
| Urine exposure and renal PK of lotilaner | PK parameters for urine sampling methods will be evaluated and include fe. | 3 days |
| Urine exposure and renal PK of lotilaner | PK parameters for urine sampling methods will be evaluated and include CLr0-48. | 3 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include Cmax at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include Tmax at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include Tlag at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include AUC0-168 at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include AUC0-2880 at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include AUC0-t at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include AUC0-inf at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include CL/F at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include Vz/F at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include Thalf at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include λz at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include AUC%extrap at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include MRT0-t at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include Rac at various times | up to 151 days |
| Impact of fasting on the PK of lotilaner | PK parameters will be evaluated for lotilaner following dosing with food and under fasting conditions. Parameters include Ctrough at various times | up to 151 days |