A Study to Evaluate Safety and PK of Multiple Doses of LT3001 Drug Product and Drug-drug Interaction in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
This Phase 1 study is planned to establish the clinical safety and pharmacokinetics profile of multiple dose of LT3001 drug product and to investigate drug interactions of LT3001 with potential concomitant medications in healthy subjects.

Detailed Description
-----------------
This study is a two-part study. Part A is double-blind, placebo-controlled, and will examine the safety and PK profiles of multiple doses of LT3001 drug product in healthy subjects. Part B is open-label and will assess the safety and PK of LT3001 when coadministered with aspirin, clopidogrel, apixaban or dabigatran.

Official Title
-----------------
Double-Blind, Randomized, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of LT3001 Drug Product and Drug-Drug Interaction in Healthy Adult Subjects

Conditions
-----------------
Acute Ischemic Stroke

Intervention / Treatment
-----------------
* Drug: LT3001 drug product
* Drug: Placebo
* Drug: Aspirin
* Drug: Clopidogrel
* Drug: Apixaban
* Drug: Dabigatran


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject's body weight is ≥50 kg and BMI is within the range of 18 to 32 Subject is a healthy volunteer. Subject's PT, aPTT, and TT are within the normal laboratory range. Subject is a nonsmoker Exclusion Criteria: Subject has a current or recent history of regular alcohol consumption. Subjects who are enrolled in Part B and allergic to acetylsalicylic acid, other salicylates, clopidogrel, thienopyridines (eg, ticlopidine, prasugrel), apixaban or dabigatran. Part B Cohort 2 only: subjects who are poor metabolizers of clopidogrel (CYP2C19*2/*2, *2/*3, or *3/*3 genotype) Subject has a presence or history of coagulation abnormality. Subjects need to receive a surgery or clinical procedures associated with high bleeding risk. Subject has a history of minor bleeding episodes, eg, epistaxis, rectal bleeding, gingival bleeding. Subject has a history of peptic ulcer or gastrointestinal bleeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part A: parallel Part B: single group
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A - LT3001 Drug Product<br>Multiple doses of LT3001 administered by intravenous infusion | Drug: LT3001 drug product<br>* Multiple doses of LT3001 drug product administered by intravenous infusion<br>* Other names: LT3001 injection;|
| Placebo Comparator: Part A - Placebo<br>Multiple doses of Placebo administered by intravenous infusion | Drug: Placebo<br>* Multiple doses of Placebo administered by intravenous infusion<br>* Other names: Placebo of LT3001 drug product;|
| Experimental: Part B - LT3001 and Aspirin<br>Multiple doses of LT3001 and Aspirin administered | Drug: LT3001 drug product<br>* Multiple doses of LT3001 drug product administered by intravenous infusion<br>* Other names: LT3001 injection;Drug: Aspirin<br>* Loading and maintenance doses of Aspirin administered by oral<br>* Other names: Aspirin tablet;|
| Experimental: Part B - LT3001 and Clopidogrel<br>Multiple doses of LT3001 and Clopidogrel administered | Drug: LT3001 drug product<br>* Multiple doses of LT3001 drug product administered by intravenous infusion<br>* Other names: LT3001 injection;Drug: Clopidogrel<br>* Loading and maintenance doses of Clopidogrel administered by oral<br>* Other names: Clopidogrel tablet;|
| Experimental: Part B - LT3001 and Apixaban<br>Multiple doses of LT3001 and Apixaban administered | Drug: LT3001 drug product<br>* Multiple doses of LT3001 drug product administered by intravenous infusion<br>* Other names: LT3001 injection;Drug: Apixaban<br>* Multiple doses of Apixaban administered by oral<br>* Other names: Eliquis®;|
| Experimental: Part B - LT3001 and Dabigatran<br>Multiple doses of LT3001 and Dabigatran administered | Drug: LT3001 drug product<br>* Multiple doses of LT3001 drug product administered by intravenous infusion<br>* Other names: LT3001 injection;Drug: Dabigatran<br>* Multiple doses of Dabigatran administered by oral<br>* Other names: Pradaxa®;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | To evaluate the safety and tolerability of LT3001 administered alone or with Aspirin, Clopidogrel, Apixaban, Dabigatran determined by number and severity of adverse events from the time of dosing up to 16 days post-dose. | 16 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in coagulation | To evaluate the safety of LT3001 administered alone or with Aspirin, Clopidogrel, Apixaban, Dabigatran determined by coagulation test from baseline up to 16 days post-dose. | 16 days | 
| Changes from baseline in platelet function test | To evaluate the safety of LT3001 administered alone or with Aspirin, Clopidogrel, Apixaban, Dabigatran determined by platelet function from baseline up to 16 days post-dose. | 16 days | 
| Plasma PK parameters of LT3001 - Cmax | Plasma concentrations of LT3001 and derived PK parameters up to 10 days after a single dose or multiple doses intravenous infusion of LT3001. | 10 days | 
| Plasma PK parameters of LT3001 - Tmax | Plasma concentrations of LT3001 and derived PK parameters up to 10 days after a single dose or multiple doses intravenous infusion of LT3001. | 10 days | 
| Plasma PK parameters of LT3001 - AUC | Plasma concentrations of LT3001 and derived PK parameters up to 10 days after a single dose or multiple doses intravenous infusion of LT3001. | 10 days | 
| Plasma PK parameters of Aspirin - Cmax | Plasma concentrations of Aspirin and derived PK parameters up to 8 days after multiple doses of Aspirin administered (alone or with LT3001). | 8 days | 
| Plasma PK parameters of Aspirin - Tmax | Plasma concentrations of Aspirin and derived PK parameters up to 8 days after multiple doses of Aspirin administered (alone or with LT3001). | 8 days | 
| Plasma PK parameters of Aspirin - AUC | Plasma concentrations of Aspirin and derived PK parameters up to 8 days after multiple doses of Aspirin administered (alone or with LT3001). | 8 days | 
| Plasma PK parameters of Clopidogrel - Cmax | Plasma concentrations of Clopidogrel and derived PK parameters up to 10 days after multiple doses of Clopidogrel administered (alone or with LT3001). | 10 days | 
| Plasma PK parameters of Clopidogrel - Tmax | Plasma concentrations of Clopidogrel and derived PK parameters up to 10 days after multiple doses of Clopidogrel administered (alone or with LT3001). | 10 days | 
| Plasma PK parameters of Clopidogrel - AUC | Plasma concentrations of Clopidogrel and derived PK parameters up to 10 days after multiple doses of Clopidogrel administered (alone or with LT3001). | 10 days | 
| Plasma PK parameters of Apixaban - Cmax | Plasma concentrations of Apixaban and derived PK parameters up to 8 days after multiple doses of Apixaban administered (alone or with LT3001). | 8 days | 
| Plasma PK parameters of Apixaban - Tmax | Plasma concentrations of Apixaban and derived PK parameters up to 8 days after multiple doses of Apixaban administered (alone or with LT3001). | 8 days | 
| Plasma PK parameters of Apixaban - AUC | Plasma concentrations of Apixaban and derived PK parameters up to 8 days after multiple doses of Apixaban administered (alone or with LT3001). | 8 days | 
| Plasma PK parameters of Dabigatran - Cmax | Plasma concentrations of Dabigatran and derived PK parameters up to 8 days after multiple doses of Dabigatran administered (alone or with LT3001). | 8 days | 
| Plasma PK parameters of Dabigatran - Tmax | Plasma concentrations of Dabigatran and derived PK parameters up to 8 days after multiple doses of Dabigatran administered (alone or with LT3001). | 8 days | 
| Plasma PK parameters of Dabigatran - AUC | Plasma concentrations of Dabigatran and derived PK parameters up to 8 days after multiple doses of Dabigatran administered (alone or with LT3001). | 8 days |