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

Ionis Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Abnormalities, Cardiovascular

Treatments: Drug: Placebo; Drug: Moxifloxacin; Drug: Volanesorsen

Study type: Interventional

Funder types: Industry

Identifiers

NCT02910635

ISIS 304801-CS13

Details and patient eligibility

About

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.

Enrollment: 52 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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52 participants in 5 patient groups, including a placebo group

Volanesorsen, Intravenous (IV)

Experimental group

Description:

300 mg of volanesorsen (ISIS 304801) administered Intravenous (IV) single dose

Treatment:

Drug: Volanesorsen

Volanesorsen, Subcutaneous (SQ)

Experimental group

Description:

300 mg of volanesorsen (ISIS 304801) administered Subcutaneous (SQ) single dose

Treatment:

Drug: Volanesorsen

Moxifloxacin Hydrochloride

Active Comparator group

Description:

Moxifloxacin Hydrochloride 400 mg tablet administered orally, Single Dose

Treatment:

Drug: Moxifloxacin

Placebo Intravenous (IV) single dose

Placebo Comparator group

Description:

Administered as normal saline (0.9% Sodium Chloride)

Treatment:

Drug: Placebo

Placebo Subcutaneous (SC) single dose

Placebo Comparator group

Description:

Administered as normal saline (0.9% Sodium Chloride)

Treatment:

Drug: Placebo