A Phase II Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Escalation Study of NNZ-2566 in Rett Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 3
- 主要终点
- Adverse events
研究概览
简要总结
The purpose of this study is to determine whether NNZ-2566 is safe and well tolerated in the treatment of Rett Syndrome in adolescent and adult females.
详细描述
Rett Syndrome is a developmental disorder primarily if not exclusively affecting females. The disorder is characterized by apparent normal development in early infancy (6-18 months), followed by a period of regression with onset of systemic and neurological signs. The CNS symptoms of Rett Syndrome include learning disability, autism and epilepsy and these can be severe and highly debilitating. Affected individuals also show signs of autonomic dysfunction, reflected in cardiovascular and respiratory abnormalities. There is no currently effective treatment for Rett Syndrome.
This study will investigate the safety and tolerability of treatment with oral administration of NNZ-2566 at 35 mg/kg or 70 mg/kg BID in adolescent or adult females with Rett Syndrome. The study also will also investigate measures of efficacy during treatment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 45 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Rett Syndrome with proven mutation of the MeCP2 gene
- •Age 16 to 45 years
- •Severity rating of between 10 and 36 (Rett Syndrome Natural History/Clinical Severity Scale)
- •Concomitant medications must be stable for >4 weeks prior to enrollment. The following concomitant medications are permitted: anticonvulsants which do not have liver inducing effects; beta-blockers; medications for the treatment of gastroesophageal reflux disease (GERD); medications for the treatment of chronic respiratory conditions such as asthma; medications for the treatment of anxiety, of depression and of psychosis, hormonal contraceptives. Melatonin for difficulties with sleep onset.
- •Ability to swallow study medication provided as a liquid solution, or via gastrostomy tube
排除标准
- •No detectable abnormality of the EEG during screening period
- •Actively undergoing regression
- •QTcF exclusions (any of the following): baseline/screening QT/QTcF interval of 450 msec; history of risk factors for torsade de pointes (e.g. heart failure, hypokalemia (serum potassium at screening < 3.0 mmol/L) or family history of long QT syndrome; QT/QTcF prolongation previously or currently controlled with medication
- •Current treatment with insulin
- •Hgb A1C values outside the normal reference range at screening
- •Current or past treatment with IGF-1
- •Current or past treatment with growth hormone
- •Current treatment with N-methyl-D-aspartate (NMDA) antagonists
- •Current or planned use of non-medication based interventional therapy during the period of the study (defined as 4-6 week screening period followed by 4 week dosing and 2 week follow-up period)
- •Current clinically significant cardiovascular, renal, hepatic or respiratory disease
- •Gastrointestinal disease which may interfere with the absorption, distribution, metabolism or excretion of the the study medication
- •History of, or current cerebrovascular disease or brain trauma
- •History of, or current significant endocrine disorder e.g. hypo or hyperthyroidism or diabetes mellitus
- •History of, or current malignancy
- •Clinically significant abnormalities in safety laboratory tests, vital signs or ECG, as measured at screening or baseline
- •Confirmed pregnancy
- •Significant hearing and/or visual impairment that may affect ability to complete the test procedures
- •Enrollment in another clinical trial within the previous 30 days
- •Previously randomized in this clinical trial
- •Allergy to strawberries
研究组 & 干预措施
NNZ-2566
Glycyl-L-2-Methylpropyl-L-Glutamic Acid
干预措施: NNZ-2566 (Drug)
Placebo (strawberry flavored solution)
Strawberry flavored solution and Water for Injection
干预措施: Placebo (Drug)
结局指标
主要结局
Adverse events
时间窗: Through to Day 40
Incidence of adverse events (AE), including Serious adverse events (SAE), will be evaluated between the two NNZ-2566 doses and placebo. SAEs will be examined from randomization through to Day 40. AEs will be examined from dosing through to Day 40.
次要结局
- Change in EEG activity(Baseline through to Day 40)
- Behavior(Baseline through to Day 40)
- Physiological changes(Baseline through to Day 40)
- Global and Functional outcome Measures(Baseline through to Day 40)