A Randomized Double-Blinded Crossover Trial to Define the ECG Effects of Mipomersen (ISIS 301012) Using a Therapeutic and Supratherapeutic Dose Compared to Placebo and Moxifloxacin (a Positive Control) in Healthy Men and Women: A Thorough ECG Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- change from baseline in QTcF (corrected Frederica's CT interval)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
mipomersen IV (supra-therapeutic dose)
200 mg of mipomersen IV / placebo SC
干预措施: mipomersen sodium (Drug)
mipomersen IV (supra-therapeutic dose)
200 mg of mipomersen IV / placebo SC
干预措施: placebo (Drug)
mipomersen SC (therapeutic dose)
200 mg of mipomersen SC / placebo IV
干预措施: mipomersen sodium (Drug)
mipomersen SC (therapeutic dose)
200 mg of mipomersen SC / placebo IV
干预措施: placebo (Drug)
moxifloxacin IV
400 mg of moxifloxacin IV / placebo SC
干预措施: moxifloxacin hydrochloride (Avelox®) (Drug)
moxifloxacin IV
400 mg of moxifloxacin IV / placebo SC
干预措施: placebo (Drug)
placebo
Placebo IV / placebo SC
干预措施: placebo (Drug)
结局指标
主要结局
change from baseline in QTcF (corrected Frederica's CT interval)
时间窗: ECG monitoring up to 24 hours post dose
次要结局
- change in ECG morphological patterns(ECG monitoring up to 24 hours post dose)
- ECG intervals (QTcB (corrected Bazett's QT interval), HR (heart rate, PR, QRS, and QT)(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)