A Phase 1, Randomized, Placebo-and Positive-Controlled Crossover Study to Determine the Effect of Single-Dose GC4419 on QTc Interval in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
This is a partially double-blind study in healthy adult subjects, which will be conducted as a placebo- and active-controlled, single-dose, crossover study. Twenty-eight subjects will be enrolled to ensure 24 subjects on all study periods. All subjects will receive all 3 study treatments (GC4419, placebo and moxifloxacin) in randomized sequence. Cardiodynamic assessment using continuous ECG recordings (Holters) will be performed for approximately 26 hours on the day of dosing (Day 1) in each study period. ECGs will be extracted serially pre- and post-dose and predefined timepoints at which subjects will be supinely resting. Subjects will be supinely resting for at least 10 minutes prior to and 5 minutes after each nominal timepoint for ECG extraction. Blood draws for PK will be performed in all periods at the same timepoints and always after ECG extraction. Subjects will be domiciled in the clinic from noon/afternoon of the day before dosing (Day -1) until completion of safety procedures on Day 2 in each study period. All subjects (including subjects who terminate the study early) will return to the clinical research unit (CRU) 14 (± 1) days after the last administration of study treatment for follow-up procedures and to determine if any Adverse Event (AE) has occurred since the last study visit.

Official Title
-----------------
A Phase 1, Randomized, Placebo-and Positive-Controlled Crossover Study to Determine the Effect of Single-Dose GC4419 on QTc Interval in Healthy Volunteers

Conditions
-----------------
Healthy Volunteers, Healthy

Intervention / Treatment
-----------------
* Drug: GC4419 IV
* Drug: Placebo
* Drug: Oral moxifloxacin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy, adult, male or female, 18-55 years of age Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dose. Must weigh at least 60 kg for males or 52 kg for females and have a body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECGs For a female of childbearing potential: either be sexually inactive as a voluntary lifestyle choice for at least 1 year prior to first dosing until 21 days following last dosing or be using an acceptable birth control method For a female of non-childbearing potential: must have undergone an acceptable sterilization procedure or be postmenopausal for at least 1 year prior to the first dose Willing and able to comply with the protocol. Seated blood pressure between 90/40 mmHg and 140/90 mmHg Has serum potassium, calcium, and magnesium levels within the normal range at screening. Exclusion Criteria: History or presence of clinically significant medical or psychiatric condition, disease or illness History or presence of alcoholism or drug abuse within the past 2 years History or presence of hypersensitivity to the study drugs History of significant multiple and/or severe allergies Female subjects who are pregnant or lactating. Positive results at screening for human immunodeficiency virus (HIV), syphilis, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV). Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications 14 days prior to the first dose of study drug and throughout the study. Any drugs known to be significant inhibitors or inducers of CYP enzymes and/or P-gp, including St. John's Wort, for 28 days prior to the first dose of study drug and throughout the study. Has been on a diet incompatible with the on-study diet, within the 28 days prior to the first dose of study drug, and throughout the study. Donation of blood or significant blood loss within 56 days Plasma donation within 7 days prior to the first dose of study drug. Has had surgery or any medical condition which may affect the absorption, distribution, metabolism, or elimination of the study drug within 6 months. Participation in another clinical trial within 28 days Participation in a previous clinical trial where subject received GC4419. History or presence of: hypokalemia, risk factors for Torsades de Pointes , sick sinus syndrome, second, or third degree atrioventricular block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged QT interval, or conduction abnormalities; repeated or frequent syncope or vasovagal episodes; hypertension, angina, bradycardia, or severe peripheral arterial circulatory disorders.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GC4419 IV<br> | Drug: GC4419 IV<br>* 50mg infused IV over 15 minutes<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Infused IV over 15 minutes<br>|
| Active Comparator: Oral moxifloxacin<br> | Drug: Oral moxifloxacin<br>* 400 mg tablet orally with 250 mL room temperature water<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in QT interval corrected for heart rate using the Fridericia formula (QTcF) |  | From 45 minute pre-dose to 24 hours post dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Healthy Adult, Superoxide Dismutase, Free Radical Dismutase, Cardiodynamic Assessment