A Six Week Pharmacokinetic Study of TP-03 in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
Pharmacokinetic Study to Evaluate the Whole Blood Pharmacokinetics of TP-03 Following Six Week Topical Ocular Administration.

Detailed Description
-----------------
This is a single-center, open-label, single-arm study. A single drop of the ophthalmic solution will be instilled in each eye on the morning of Day 1 and then twice a day (in the morning and in the evening, approximately 12 hours apart) starting on Day 2 for 40 consecutive days (Days 2 to 41). Thereafter, a single drop of the ophthalmic solution will be instilled in each eye on the morning of Day 42, for a total of 82 consecutive doses administered in each eye. The doses of Days 1, 2 (morning), 41 (evening), and 42 will be self-administered under supervision of the site staff at the clinical site. All remaining doses will be self-administered at home. Throughout the study, PK blood samples will be collected and safety assessments will be performed.

Official Title
-----------------
Pharmacokinetic Study to Evaluate the Whole Blood Pharmacokinetics of TP-03 Following Six Week Topical Ocular Administration

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: TP-03 (Lotilaner Ophthalmic Solution), 0.25%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of signed and dated informed consent form (ICF) Stated willingness to comply with all study procedures and availability for the duration of the study Healthy adult male or female If female, meets one of the following criteria: Is of childbearing potential and agrees to use an acceptable contraceptive method. Or Male partner has had a vasectomy less than 6 months prior to dosing and the female subject agrees to use an additional acceptable contraceptive method from the first study drug administration until 112 days after the last study drug administration Or Is of non-childbearing potential, defined as surgically sterile (ie, has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is in a post-menopausal state (ie, at least 1 year without menses without an alternative medical condition prior to the first study drug administration) Aged at least 18 years Non- or ex-smoker (An ex-smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration) 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 lactating Female who is pregnant according to the pregnancy test at screening or prior to the first study drug administration Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease Significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic) Any clinically significant illness in the 28 days prior to the first study drug administration Use of any prescription drugs (with the exception of hormonal contraceptives or hormone replacement therapy) in the 28 days prior to the first study drug administration Use of St. John's wort in the 28 days prior to the first study drug administration History of any ocular surgery or laser within the past 12 months prior to the first study drug administration Have used artificial eyelashes, eyelash extensions or had other cosmetic eyelash or eyelid procedures (e.g., eyeliner tattooing, eyelash tinting, eyelash curling perm, etc.) within 7 days prior to Screening or unwilling to forego their use during the study Presence of clinically significant ocular surface diseases including blepharitis, dry eye, corneal scars, and pterygium, or any ocular abnormalities identified at Screening Presence of acute ocular infection or inflammation at Screening, or required use of eye drops Any history of tuberculosis Positive screening results to HIV Ag/Ab combo, hepatitis B surface antigen or hepatitis C virus tests Intake of an Investigational Product (IP) in the 28 days prior to the first study drug administration Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the 56 days prior to the first study drug administration

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: This is a single-center, open-label, single-arm study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TP-03 (Lotilaner Ophthalmic Solution), 0.25%<br>TP-03, topical ocular administration in healthy adults. Single and multiple doses for 42 days. | Drug: TP-03 (Lotilaner Ophthalmic Solution), 0.25%<br>* A single drop of the ophthalmic solution will be instilled in each eye on the morning of Day 1 and then twice a day (in the morning and in the evening, approximately 12 hours apart) starting on Day 2 for 40 consecutive days (Days 2 to 41). Thereafter, a single drop of the ophthalmic solution will be instilled in each eye on the morning of Day 42, for a total of 82 consecutive doses administered in each eye.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner Cmax at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner Tmax at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner Tlag at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner AUC0-168 at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner AUC0-2880 at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner AUC0-t at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner AUC0-inf at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner CL/F at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner Vz/F at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner eff at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner Thalf at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner λz at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner AUC%extrap at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner MRT0-t at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner Rac at various times | 42 Days | 
| To evaluate the concentration of lotilaner in blood multiple doses of TP-03, 0.25% in whole blood following topical ocular administration in healthy adult subjects for 42 days. | The primary PK endpoints following single and multiple dose administration will include whole blood PK parameters for lotilaner Ctrough at various times | 42 Days | 
| Incidence of treatment emergent adverse events (TEAEs) | Safety will be evaluated through the incidence rate of TEAEs | 42 Days | 
| Clinically significant changes from Baseline chemistry laboratory tests | Evaluate the safety of TP-03 through clinically significant changes from Baseline chemistry laboratory tests | 42 Days | 
| Clinically significant changes from Baseline hematology laboratory tests | Evaluate the safety of TP-03 through clinically significant changes from Baseline hematology laboratory tests | 42 Days | 
| Clinically significant changes from Baseline physical examinations | Safety will be evaluated through review of clinically significant changes in physical examinations from Baseline | 42 Days | 
| Clinically significant changes from Baseline electrocardiograms (ECGs) | Safety will be evaluated through review of clinically significant changes in electrocardiograms from Baseline | 42 Days | 
| Clinically significant changes from Baseline vitals | Safety will be evaluated through review of 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]) from Baseline | 42 Days | 
| Clinically significant changes from Baseline corrected distance visual acuity | Safety will be evaluated through review of clinically significant changes in corrected distance visual acuity from Baseline | 42 Days | 
| Clinically significant changes from Baseline non-mydriatic fundus photographs | Safety will be evaluated through review of clinically significant changes in non-mydriatic fundus photographs from Baseline | 42 Days | 
| Clinically significant changes from Baseline intraocular pressure (IOP) measurement | Safety will be evaluated through review of clinically significant changes in IOP from Baseline | 42 Days |