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

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

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.

Study Overview

• Status: Completed
• Conditions: Abnormalities, Cardiovascular
• Intervention / Treatment: Drug: Placebo; Drug: Volanesorsen; Drug: Moxifloxacin

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volanesorse plasma pharmacokinetics (PK)	Area under the plasma concentration time curve from time 0 to 24 hours (AUC 0-24h)	0 to 24 hours

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.
• Collaborators: Akcea Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2016
• Primary Completion (Actual): December 20, 2016
• Study Completion (Actual): December 20, 2016

Study Registration Dates

• First Submitted: September 9, 2016
• First Submitted That Met QC Criteria: September 19, 2016
• First Posted (Estimate): September 22, 2016

Study Record Updates

• Last Update Posted (Actual): January 28, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Thorough QTc, Therapeutic dose, supra therapeutic dose
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: ISIS 304801-CS13