Thorough QT (TQT) Study to Evaluate the Effect of LC350189 on Cardiac Repolarization in Healthy Male and Female Subjects

Study Overview
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Brief Summary
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This is a Phase 1, single-center, randomized, partially double-blind, placebo- and positive controlled, 4-way crossover study to evaluate the effect of a therapeutic and a supratherapeutic dose of LC350189 on the QTcF in healthy male and female subjects.

Official Title
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A Single-Dose, Randomized, Double-Blind, Placebo- and Positive-Controlled, 4-Way Crossover Study to Evaluate the Effect of LC350189 on the QTc (Corrected QT) Interval in Healthy Adult Subjects

Conditions
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Hyperuricemia, Gout, Qt Interval, Variation in

Intervention / Treatment
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* Drug: LC350189 200mg
* Drug: Placebo
* Drug: Moxifloxacin 400mg
* Drug: LC350189 600mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is 18 to 55 years of age, inclusive, with a body mass index (BMI) 18 to 33 kg/m2, inclusive, at screening. The subject is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at screening. The subject is able to provide written informed consent and agrees to comply with all protocol requirements. Exclusion Criteria: The subject has a history of risk factors for torsades de pointes, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, or angina. The subject has a family history of long QT syndrome, Brugada syndrome, or sudden death. The subject has a resting HR of <40 bpm or >100 bpm when vital signs are measured at screening or check-in. The subject has history or presence of unstable cardiovascular disease, including myocardial infarction, cardiac arrhythmia, or cerebrovascular disease (eg, cerebrovascular accident/stroke or transient ischemic attack). The subject has a history of other acute or chronic cardiovascular disease or coronary revascularization surgery (eg, coronary artery bypass graft, percutaneous transluminal coronary angioplasty). The subject uses a cardiac pacemaker. The subject has a history of any other medical, psychological, or social condition that, in the opinion of the investigator or the medical monitor, would prevent the subject from fully participating in the study, would represent a concern for study compliance, or would constitute a safety concern to the subject.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 4-way cross over
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment T (Therapeutic dose)<br>Single oral dose of 200 mg LC350189 (1 × 200 mg tablet) and 2 × placebo tablets. | Drug: LC350189 200mg<br>* Subject will receive an LC350189 200mg as single-dose on Day 1(Period 1) or Day 5(Period 2) or Day 9(Period 3) or Day 13(Period 4)<br>* Other names: LC350189 (therapeutic dose);|
| Experimental: Treatment ST (Supratherapeutic dose)<br>Single oral dose of 600 mg LC350189 (3 × 200 mg tablets). | Drug: LC350189 600mg<br>* Subject will receive an LC350189 600mg as single-dose on Day 1(Period 1) or Day 5(Period 2) or Day 9(Period 3) or Day 13(Period 4)<br>* Other names: LC350189 (supratherapeutic dose);|
| Placebo Comparator: Treatment P (Placebo)<br>Single oral dose of 3 × placebo tablets. | Drug: Placebo<br>* Subject will receive a Placebo as single-dose on Day 1(Period 1) or Day 5(Period 2) or Day 9(Period 3) or Day 13(Period 4)<br>* Other names: Placebo control;|
| Active Comparator: Treatment M (positive control)<br>Single oral dose of moxifloxacin 400 mg (1 × 400 mg tablet; open label) | Drug: Moxifloxacin 400mg<br>* Subject will receive a Moxifloxacin 400mg as single-dose on Day 1(Period 1) or Day 5(Period 2) or Day 9(Period 3) or Day 13(Period 4)<br>* Other names: Positive control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The placebo-corrected change from baseline in QTcF | QTcF will be analyzed using concentration-QT (cQT) modeling | Before dosing (Baseline) through 24 hours after the dose on Day 1 in each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The placebo-corrected change from baseline in HR (heart rate) | HR will be evaluated at each postdose time point | Before dosing (Baseline) through 24 hours after the dose on Day 1 in each treatment period | 
| The placebo-corrected change from baseline in PR | PR will be evaluated at each postdose time point | Before dosing (Baseline) through 24 hours after the dose on Day 1 in each treatment period | 
| The placebo-corrected change from baseline in QRS | QRS will be evaluated at each postdose time point | Before dosing (Baseline) through 24 hours after the dose on Day 1 in each treatment period |