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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Enrollment
- 52
- Locations
- 1
- Primary Endpoint
- Placebo corrected change from baseline in QTcF (corrected Frederica's CT Interval)
Study Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
Volanesorsen, Intravenous (IV)
300 mg of volanesorsen (ISIS 304801) administered Intravenous (IV) single dose
Intervention: Volanesorsen (Drug)
Volanesorsen, Subcutaneous (SQ)
300 mg of volanesorsen (ISIS 304801) administered Subcutaneous (SQ) single dose
Intervention: Volanesorsen (Drug)
Moxifloxacin Hydrochloride
Moxifloxacin Hydrochloride 400 mg tablet administered orally, Single Dose
Intervention: Moxifloxacin (Drug)
Placebo Intravenous (IV) single dose
Administered as normal saline (0.9% Sodium Chloride)
Intervention: Placebo (Drug)
Placebo Subcutaneous (SC) single dose
Administered as normal saline (0.9% Sodium Chloride)
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Placebo corrected change from baseline in QTcF (corrected Frederica's CT Interval)
Time Frame: 24 Hours
ECG monitoring up to 24 hours post dose
Secondary Outcomes
- Placebo corrected change from baseline heart rate (HR, PR and QRS)(24 Hours)