A Pharmacokinetic Study of TP-05 in Healthy Subjects

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: TP-05 (lotilaner oral capsules); Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Altasciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TP-05 SAD; Single dose of TP-05 (lotilaner oral capsules) at 4 dose levels in ascending order	Drug: TP-05 (lotilaner oral capsules); TP-05 (lotilaner oral capsules)
Experimental: Placebo SAD; Single dose of Placebo	Drug: Placebo; Placebo to match TP-05 (lotilaner oral capsules)
Experimental: TP-05 MAD; Four doses of TP-05 (lotilaner oral capsules) at 3 dose levels in ascending order	Drug: TP-05 (lotilaner oral capsules); TP-05 (lotilaner oral capsules)
Experimental: Placebo MAD; Four doses of Placebo	Drug: Placebo; Placebo to match TP-05 (lotilaner oral capsules)
Experimental: TP-05 Fasted; Single dose of TP-05 (lotilaner oral capsules) in a fasted state	Drug: TP-05 (lotilaner oral capsules); TP-05 (lotilaner oral capsules)
Experimental: Placebo Fasted; Single dose of placebo in a fasted state	Drug: Placebo; Placebo to match TP-05 (lotilaner oral capsules)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Tarsus Pharmaceuticals, Inc.
• Investigators: Study Director: Jeremy Lim, Tarsus Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2021
• Primary Completion (Actual): March 25, 2022
• Study Completion (Actual): July 25, 2022

Study Registration Dates

• First Submitted: July 22, 2021
• First Submitted That Met QC Criteria: November 17, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: TRS-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No