An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 4
- 主要终点
- Safety and Tolerability
研究概览
简要总结
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Phelan-McDermid Syndrome.
详细描述
The primary purpose of this study is to investigate the safety, tolerability and pharmacokinetics of treatment with NNZ-2591 oral solution in children and adolescents with Phelan-McDermid Syndrome. The secondary purpose is to investigate measures of efficacy. Subjects will receive treatment with NNZ-2591 oral solution (50 mg/mL) doses for a total of 13 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of PMS with a documented disease-causing genetic abnormality of SHANK
- •Males or females aged 3-12 years.
- •Body weight of 12 kg or higher at Screening.
- •Subjects with a Clinical Global Impression - Severity (CGI-S) score of 4 or greater at the Screening visit.
- •Not actively undergoing regression or loss of skills, defined as no persistent loss of previously acquired developmental skills for a period within 3 months of the Screening visit
- •Each subject must be able to swallow the study medication provided as a liquid solution.
- •Caregiver(s) must have sufficient English language skills.
排除标准
- •Body weight < 12kg at screening
- •Clinically significant abnormalities in safety laboratory tests and vital signs at Screening.
- •Abnormal QTcF interval or prolongation at Screening.
- •Any other clinically significant finding on ECG at the Screening visit.
- •Positive for severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) and previous COVID 19 infection with last 12 months that required hospitalization
- •Unstable or changes Psychotropic treatment 2 weeks prior to screening .
- •Excluded concomitant treatments.
- •Actively undergoing regression or loss of skills.
- •Unstable seizure profile.
- •Current clinically significant renal conditions and abnormalities
- •Current clinically significant cardiovascular, renal, hepatic, gastrointestinal, respiratory, endocrine disease, or clinically significant organ impairment.
- •Current clinically significant hypo or hyperthyroidism, Type 1 or Type 2 diabetes mellitus requiring insulin (whether well controlled or uncontrolled), or uncontrolled Type 1 or Type 2 diabetes.
- •Has planned surgery during the study.
- •History of, or current, cerebrovascular disease or brain trauma.
- •History of, or current catatonia or catatonia-like symptoms.
- •History of, or current, malignancy.
- •Current major or persistent depressive disorder (including bipolar depression).
- •Significant, uncorrected visual or uncorrected hearing impairment.
- •Allergy to strawberry.
- •Positive pregnancy test
- •Subject is judged by the Investigator or Medical Monitor to be inappropriate for the study
研究组 & 干预措施
NNZ-2591
NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.
干预措施: NNZ-2591 (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: 13 weeks
To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.
Pharmacokinetic - Mean AUC24
时间窗: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.
Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.
Pharmacokinetic - t1/2
时间窗: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.
Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.
次要结局
- CIC(CIC was assessed at Week13/EOT)
- CGI-I(CGI-I was assessed at Weeks 6, 13/EOT & 15. Overall improvement scores relate to Week 13/EOT visit.)
- Top 3 Concerns(Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall improvement score.)
- MB-CDI(Change from baseline (visit 3, week 0) to visit 13/EOT (week 16).)
- CGI-S(Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).)
- ORCA(Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in Total Score.)
- ABC-2(Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.)
- CSHQ(Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.)
- GIHQ(Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.)
- VABS-3(Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in composite standard score.)
- QL-Disability(Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall score score.)
- ICND(Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall quality of life rating score.)
- PMS-DSRS(Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall severity score.)
- Behavior Problems Inventory - Short Form(Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.)