Healthy
Conditions
Keywords
antisense, ApoB (Apolipoprotein B), LDL (low density lipoprotein), thorough QT
Brief summary
To assess the electrocardiogram (ECG) effects of mipomersen administered as a 200-mg subcutaneous (SC) therapeutic and a 200-mg intravenous (IV; \[2-hour infusion\]) supra-therapeutic dose relative to placebo in healthy adult male and female subjects; and to evaluate the safety and pharmacokinetics (PK) of mipomersen when administered as a single therapeutic (200 mg) SC and a single, supra-therapeutic (200 mg) IV dose.
Detailed description
This will be a randomized, double-blind, single-site, crossover study in healthy male and female subjects to determine if mipomersen administered as a single therapeutic (200 mg) SC and a single supra-therapeutic (200 mg) IV dose delays cardiac repolarization as determined by the measurement of QT/corrected QT (QTc) interval. A total of 60 healthy male and female subjects will be enrolled in this 4-way crossover study, randomly assigned to 1 of 8 treatment sequences, and cross over into 4 treatment periods where each subject will receive both a single SC injection and a single IV infusion during each period.
Interventions
200 mg of mipomersen intravenous (IV) (single dose)
DRUGmoxifloxacin hydrochloride (Avelox®)
400 mg of moxifloxacin intravenous (IV) single dose
DRUGplacebo
placebo intravenous (IV) single dose
Sponsors
Ionis Pharmaceuticals, Inc.
Kastle Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Written informed consent provided before any study-related procedures are performed. * Body mass index (BMI) of 19 to 32 kg/m2 inclusive. * Subjects can not have consumed nicotine or nicotine-containing products for at least 6 months before Screening. * Subjects are nonpregnant and nonlactating, surgically sterile, postmenopausal, abstinent, or subject or partner is willing to use a reliable method of contraception during the study and 5 months after the last dose of investigational product.
Exclusion criteria
* History of risk factors for Torsades de Pointes, known Long QT Syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments or family history of Long QT or Brugada Syndrome. * Abnormal screening ECG that is interpreted by the Investigator to be clinically significant. * Use of concomitant medications (prescribed or over-the-counter), without the approval of the Investigator and Sponsor, within 7 days before the first dose of investigational product. * Clinically significant abnormal findings on the physical examination, ECG, blood pressure, heart rate, medical history, or clinical laboratory results at Screening or before dosing. * History of clinically significant allergies or hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease. * Positive test for HIV antibody, hepatitis C antibody, or hepatitis B surface antigen. * Positive test for drugs of abuse, alcohol, or cotinine at Screening or before dosing or history of drug or alcohol abuse or dependence within 1 year before Screening. * History of cancer, with the exception of basal cell carcinoma.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| change from baseline in QTcF (corrected Frederica's CT interval) | ECG monitoring up to 24 hours post dose |
Secondary
| Measure | Time frame |
|---|---|
| ECG intervals (QTcB (corrected Bazett's QT interval), HR (heart rate, PR, QRS, and QT) | ECG monitoring up to 24 hours post dose |
| change in ECG morphological patterns | ECG monitoring up to 24 hours post dose |
| Correlation between delta delta QTc interval and plasma mipomersen concentrations | ECG monitoring up to 24 hours post dose |
| Incidence of treatment-emergent Adverse Events | Assessed at each visit |
| mipomersen plasma pharmacokinetic (PK) parameters: Area Under the Curve (AUC 0-22.5h), Maximum Concentration (Cmax), Time to Maximum Concentration (Tmax) | Serial PK sampling up to 24 hours post dose |
Countries
United States
Outcome results
None listed