A Single-Blind, Randomized, Parallel Trial to Define the ECG Effects of Sancuso® (Granisetron Transdermal System) Compared to Placebo and Moxifloxacin in Healthy Men and Women
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Time-matched, placebo-corrected change from baseline in QTc based on the Fridericia correction (QTcF).
研究概览
简要总结
This study aims to evaluate the electrocardiogram (ECG) effects of Sancuso® compared to placebo and moxifloxacin in healthy subjects.
详细描述
Granisetron is a well tested and established 5-HT3 receptor antagonist used in both oral and intravenous (IV) forms. A transdermal form of granisetron (Sancuso®) was approved by the United States (US) Food and Drug Administration (FDA) in September 2008.
Many of the 5-HT3 antagonists were developed and approved before the adoption of the International Conference on Harmonisation (ICH) E14 standard on QTc and cardiac testing. The association of non-cardiac medicinal products with the potential to prolong the QT interval and induce torsades des pointes (TdP) has significant implications for the future development of medicinal products.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female subjects
- •Aged between 18 and 50 years, inclusive, at screening
- •BMI between 18.0 and 32.0 kg/m², inclusive
排除标准
- •History of drug abuse
- •Known hypersensitivity to granisetron, moxifloxacin, or related compounds, such as ciprofloxacin and levofloxacin
- •Sustained supine systolic blood pressure >140 mmHg or <100 mmHg or a diastolic blood pressure >95 mmHg at Screening or baseline
- •Pulse rate at rest of < 45 bpm or > 100 bpm
- •Abnormal Screening ECG indicating a second- or third degree AV block, or one or more of the following: QRS >120 milliseconds (ms); QTcF > 430 (males) or 450 (females) ms; PR interval >240 ms; any rhythm, other than sinus rhythm, interpreted to be clinically significant by the Investigator
- •Known history of long-QT syndrome, angina, myocardial ischemia or infarction, congestive heart failure, myocarditis, chest pain or dyspnea on exertion
- •Electrolyte disturbances (such as uncorrected hypokalemia/hyperkalemia, hypomagnesemia, hypocalcemia, or hypophosphatemia), idiopathic cardiomyopathy, unexplained syncope, hypertrophic cardiomyopathy, or sudden unexplained death at a young age (< 40 years) in a first-degree relative.
- •Has used any medications or consumed any foods contraindicated in the protocol.
研究组 & 干预措施
Treatment A: Sancuso® patch
Treatment A: Sancuso® patch (Day 1) and placebo IV (Day 3)
干预措施: granisetron (Drug)
Treatment B: IV Granisetron 10 mcg/kg
Treatment B: placebo patch (Day 1) and granisetron IV (Day 3)
干预措施: granisetron (Drug)
Treatment C: Matching placebo patch
Treatment C: placebo patch (Day 1) and placebo IV (Day 3)
干预措施: granisetron (Drug)
Treatment D: Oral Moxifloxacin 400 mg
Treatment D: placebo patch (Day 1) and oral moxifloxacin (Day 3).
干预措施: granisetron (Drug)
结局指标
主要结局
Time-matched, placebo-corrected change from baseline in QTc based on the Fridericia correction (QTcF).
时间窗: 0 to 120 hours post-dose
次要结局
- QTc with Bazett correction (QTcB), heart rate, PR interval, QRS interval, uncorrected QT interval, change in ECG morphological patterns and correlation between the QTcF change from baseline and plasma granisetron concentrations(0 to 120 hours post-dose)
- Patch adhesion and residual granisetron after patch use.(0 to 120 hours post-dose)
- Relationship of plasma concentration of granisetron versus QTcF, both graphical and mixed effects analyses of plasma concentration of granisetron versus QTcF will be performed(0 to 120 hours post-dose)