Pharmacogenomic Contribution to the Biotransformation of Trihexyphenidyl and Development of a Precision Dosing Model for Children With Dystonia and Cerebral Palsy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Difference in Cmax between CYP2D6 and CYP2C19 phenotype groups
研究概览
简要总结
This study looks at how a medicine called trihexyphenidyl works in children with dystonic cerebral palsy. The study aims to understand how trihexyphenidyl is broken down and used in the body of pediatric patients and whether this is impacted by a person's genetics. Information from this study will also be used to design future clinical trials.
详细描述
This is a 16-week single-arm nonrandomized pilot study of trihexyphenidyl in children with dystonic cerebral palsy (DCP) to 1) evaluate the pharmacokinetics (PK) of trihexyphenidyl (THP) and variation in PK parameters between CYP2D6 and CYP2C19 genotypes and 2) evaluate the feasibility of a future exposure-controlled clinical trial of THP.
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
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 5-17 years of age
- •Diagnosis of cerebral palsy and dystonia causing interference
- •Parent/legal guardian of a child with a diagnosis of cerebral palsy and dystonia
- •Parent/legal guardian is willing and able to provide informed permission/assent for the study
排除标准
- •Previously or currently taking trihexyphenidyl
- •Patients turning 18 years of age within the study period (16 weeks from Study Day 1)
- •A language barrier for the patient that precludes communication and/or the ability to complete study-related requirements
研究组 & 干预措施
Trihexyphenidyl
Participants receive trihexyphenidyl following the dose escalation schedule below:
Week 1: 0.05 mg/kg BID Week 2: 0.05 mg/kg TID Week 3: 0.1 mg/kg TID Week 4: 0.15 mg/kg TID Week 5: 0.20 mg/kg TID Week 6-15: 0.25 mg/kg TID
干预措施: Trihexyphenidyl (Drug)
结局指标
主要结局
Difference in Cmax between CYP2D6 and CYP2C19 phenotype groups
时间窗: Baseline
Cmax will be measured in first-dose pharmacokinetic study on study day 1
Recruitment percentage
时间窗: Through study completion, an average of 2 years
Measure percent of participants who were approached for the study that enrolled in the study
Difference in AUC0-n between CYP2D6 and CYP2C19 phenotype groups
时间窗: Baseline
AUC0-n will be measured in first-dose pharmacokinetic study on study day 1
Retention percentage
时间窗: Through study completion, an average of 2 years
Measure percent of participants enrolled who completed the study
Difference in AUC0-∞ between CYP2D6 and CYP2C19 phenotype groups
时间窗: Baseline
AUC0-∞ will be measured in first-dose pharmacokinetic study on study day 1
Dystonia Efficacy Measures Outcome Completion
时间窗: Through study completion, an average of 2 years
Measure percent of participants enrolled who were able to complete each dystonia efficacy measure (see secondary outcome measures)
次要结局
- Change from baseline in dystonia duration as measured by the Dyskinesia Impairment Scale (exploratory)(Baseline, 16 weeks)
- Change from baseline in dystonia as measured by the Quality of Upper Extremity Skills Test (QUEST) (exploratory)(Baseline, 16 weeks)
- Number of participants with at least one adverse event as measured by the Safety Monitoring Uniform Report Form (SMURF)(Through study completion, an average of 2 years)
- Change from baseline in dystonia amplitude as measured by the Dyskinesia Impairment Scale (exploratory)(Baseline, 16 weeks)
- Change in functional impact from baseline as measured by the Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS) (exploratory)(Baseline, 16 weeks)
- Change in priority scores in functional impact from baseline as measured by the Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS) (exploratory)(Baseline, 16 weeks)
- Change in patient-driven performance from baseline as measured by the Canadian Occupational Performance Measure (exploratory)(Baseline, 16 weeks)
- Change in patient-driven goal satisfaction from baseline as measured by the Canadian Occupational Performance Measure (exploratory)(Baseline, 16 weeks)
- Change in caregiver's perspective about their child in 4 domains: health status, comfort, wellbeing, functional abilities, and ease of caregiving from baseline as measured by Caregiver Priorities and Child Health Index of Life with Disabilities(Baseline, 16 weeks)
- Measure the acceptability of outcome measures at 16 weeks as measured by the Acceptability of Intervention Measure(16 weeks)
研究者
Rose Gelineau-Morel
Principal Investigator
Children's Mercy Hospital Kansas City