Double-blind, Randomized, Placebo- and Positive-controlled, Parallel-group Trial to Assess the Potential Electrocardiographic Effects of Rotigotine Transdermal System up to 120 cm2/54.0 mg/Day in Subjects With Advanced-stage Idiopathic Parkinson's Disease: A Thorough QT/QTc Trial.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- UCB Pharma
- 入组人数
- 130
- 试验地点
- 2
- 主要终点
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 3 Hours After Patch Application on Day 42(Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
研究概览
简要总结
The purpose of this trial is to assess whether rotigotine has an effect on the electrical activity of the heart. Moxifloxacin infusion is used as positive control to assess assay sensitivity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female at least 18 years of age
- •Advanced-stage idiopathic Parkinson's disease requiring treatment with levodopa.
- •Nonchildbearing potential
排除标准
- •Atypical Parkinson's syndrome(s).
- •History of pallidotomy, thalamotomy, deep brain stimulation, or fetal tissue transplant.
- •Significant tremor or dyskinesias.
- •Severe dysfunction of the autonomic nervous system.
- •History of transient ischemic attack or stroke within the last 12 months.
- •Conduction abnormality or relevant cardiac dysfunction and/or myocardial infarction within last 12 months.
- •History or current condition of additional risk factors for Torsade de Pointes (eg, heart failure, hypokalemia), or a family history of long QT syndrome and/or of Torsade de Pointes.
- •No stable sinus rhythm: more than 20 ectopics/h.
- •Any other clinically relevant ECG abnormality.
- •History or current condition of epilepsy and/or seizures.
- •History or current condition of atopic or eczematous dermatitis, psoriasis, or another active skin disease.
- •History or current condition of symptomatic orthostatic hypotension.
- •History or current condition of significant skin hypersensitivity to adhesives or other transdermal products or recent unresolved contact dermatitis.
- •History of glucose 6-phosphate dehydrogenase deficiency.
- •History of tendonitis or tendon rupture with quinolone antibiotics.
- •Renal or hepatic dysfunction.
- •Treatment with dopamine agonists, MAO A inhibitors, reserpine, or alpha-methyldopa
- •Therapy known to produce a nontrivial prolongation of the QT interval.
研究组 & 干预措施
Rotigotine
Rotigotine Patch
干预措施: Rotigotine (Drug)
Rotigotine
Rotigotine Patch
干预措施: Placebo infusion (Other)
Placebo
Placebo patch
干预措施: Placebo (Other)
Placebo
Placebo patch
干预措施: Moxifloxacin infusion (Drug)
Placebo
Placebo patch
干预措施: Placebo infusion (Other)
结局指标
主要结局
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 3 Hours After Patch Application on Day 42(Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 23:00h, Day 42 23:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 23:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 5 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 1:00h, Day 43 1:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 1:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 2 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 22:00h, Day 42 22:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 22:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 10 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 6:00h, Day 43 6:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 6:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 14 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 10:00h, Day 43 10:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 10:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI at Time of Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 20:00h, Day 42 20:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 20:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 1 Hour After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 21:00h, Day 42 21:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 21:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 9 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 5:00h, Day 43 5:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 5:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 19 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 15:00h, Day 43 15:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 15:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 15 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 11:00h, Day 43 11:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 11:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 17 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 13:00h, Day 43 13:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 13:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 21 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 17:00h, Day 43 17:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 17:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 22 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 18:00h, Day 43 18:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 18:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 23 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 19:00h, Day 43 19:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 19:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 4 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 00:00h, Day 43 00:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 00:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 7 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 3:00h, Day 43 3:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 3:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 11 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 7:00h, Day 43 7:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 7:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 12 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 8:00h, Day 43 8:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 8:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 16 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 12:00h, Day 43 12:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 12:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 20 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 16:00h, Day 43 16:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 16:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 6 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 2:00h, Day 43 2:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 2:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 8 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 4:00h, Day 43 4:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 4:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 13 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 9:00h, Day 43 9:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 9:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 18 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 14:00h, Day 43 14:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 14:00h.
Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 24 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
时间窗: Baseline (Day -2/ Day -1) 20:00h, Day 43 20:00h
Change in QTcI was analyzed by a parallel-group comparison between rotigotine patch and placebo patch. The QT interval refers to the respective time interval in the Electrocardiogram (ECG). The QT interval was corrected for heart rate using an individualized heart rate correction formula including QT/RR curvature optimization (QTcI). The baseline QTcI value was obtained from the average of the ECG assessment on Day -2 and Day -1. Absolute values are presented as unadjusted Mean and Standard Deviation. Baseline and final measures were taken at 20:00h.
次要结局
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 3 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 13:00h, Day 32/ Day 39 13:00h)
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI at Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 10:00h, Day 32/ Day 39 10:00h)
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 2 Hours Before Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 8:00h, Day 32/ Day 39 8:00h)
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 1 Hour After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 11:00h, Day 32/ Day 39 11:00h)
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 1 Hour Before Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 9:00h, Day 32/ Day 39 9:00h)
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 2 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 12:00h, Day 32/ Day 39 12:00h)
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 4 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 14:00h, Day 32/ Day 39 14:00h)
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 5 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 15:00h, Day 32/ Day 39 15:00h)
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 8 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 18:00h, Day 32/ Day 39 18:00h)
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 10 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 20:00h, Day 32/ Day 39 20:00h)
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 6 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 16:00h, Day 32/ Day 39 16:00h)
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 7 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 17:00h, Day 32/ Day 39 17:00h)
- Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 9 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)(Baseline (Day -2/ Day -1) 19:00h, Day 32/ Day 39 19:00h)