A Study to Evaluate the Effect of Volanesorsen on Cardiac Repolarization Conducted in Healthy Volunteers

Study Overview
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Brief Summary
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The primary objective of this study is to assess the corrected QT interval (QTc) effect of volanesorsen (ISIS 304801) administered as a 300 mg subcutaneous (SC) therapeutic and a 300 mg intravenous (IV; 2-hour infusion) supra-therapeutic dose relative to placebo in healthy adult male and female subjects.

Official Title
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A Randomized, Placebo-Controlled, Four-Period Crossover, Study to Evaluate the Effect of Volanesorsen on the QTc Interval Using a Therapeutic and Supra-Therapeutic Dose Compared With Placebo in Healthy Volunteers: a Thorough QT Study

Conditions
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Abnormalities, Cardiovascular

Intervention / Treatment
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* Drug: Volanesorsen
* Drug: Moxifloxacin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have given written informed consent and be able to comply with all study requirements Males and females aged 18-55 at the time of informed consent Females must be non-pregnant and non-lactating surgically sterile, post-menopausal or if engaged in sexual relations of childbearing potential, using an acceptable contraceptive method Males must be surgically sterile, abstinent or using an acceptable contraceptive method The subject has a BMI of 19 to 32 kg/m^2 inclusive Consumption of nicotine or nicotine-containing products for at least 6 months before Screening Exclusion Criteria: History of risk factors for Torsades de Pointes, unexplained syncope, known Long QT Syndrome, heart failure, myocardial infarction, angina, or clinical significant abnormal laboratory assessments including hypokalemia, hypocalcemia, hypercalcemia, or hypomagnesemia Abnormal screening ECG Use of concomitant medications unless authorized by the Sponsor Medical Monitor Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B Treatment with another Study Drug, biological agent, or device within one-month of Screening Tests positive for drugs of abuse or cotinine Considered unsuitable for inclusion by the Principal Investigator

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Volanesorsen, Intravenous (IV)<br>300 mg of volanesorsen (ISIS 304801) administered Intravenous (IV) single dose | Drug: Volanesorsen<br>* ISIS 304801 is supplied as 200mg of volanesorsen with 1.0mL of solution per vial<br>|
| Experimental: Volanesorsen, Subcutaneous (SQ)<br>300 mg of volanesorsen (ISIS 304801) administered Subcutaneous (SQ) single dose | Drug: Volanesorsen<br>* ISIS 304801 is supplied as 200mg of volanesorsen with 1.0mL of solution per vial<br>|
| Active Comparator: Moxifloxacin Hydrochloride<br>Moxifloxacin Hydrochloride 400 mg tablet administered orally, Single Dose | Drug: Moxifloxacin<br>* Moxifloxacin Hydrochloride 400 mg tablet administered orally, Single Dose<br>|
| Placebo Comparator: Placebo Intravenous (IV) single dose<br>Administered as normal saline (0.9% Sodium Chloride) | Drug: Placebo<br> <br> |
| Placebo Comparator: Placebo Subcutaneous (SC) single dose<br>Administered as normal saline (0.9% Sodium Chloride) | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Placebo corrected change from baseline in QTcF (corrected Frederica's CT Interval) | ECG monitoring up to 24 hours post dose | 24 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Placebo corrected change from baseline heart rate (HR, PR and QRS) | ECG monitoring 24 hours post dose | 24 Hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thorough QTc, Therapeutic dose, supra therapeutic dose