A Phase II, Randomized, Double Blind, Cross-over, Placebo-controlled Study on Norepinephrine Replenishment Therapy Using L-DOPS in Congenital Insensitivity to Pain With Anhidrosis Patients
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Incidence of Treatment-Emergent Adverse Events
研究概览
简要总结
The aim of this study is to increase norepinephrine levels in a population of young adults where NE levels are very low or undetectable. In order to achieve this, the optimal dose will be determined in a titration step. In the titration step, different doses of L-DOPS will be tested in order to find the optimal and safest dose suitable for each individual enrolled in the study. Because L-DOPS has never been used in the US in children or young adults, with this titration step investigators will also determine the safest dose for this population.
Currently, L-DOPS is being used in our center to treat othostatic hypotension in autonomic failure. The titration step for this study starts with the dose of 100 mg and increases in an escalating manner up to a maximum of 600 mg a day (see investigational brochure attached).
L-DOPS has been developed in capsules for oral used and all the previous safety data has been performed using this route. Oral route is the one that will used during study.
Carbidopa is well tolerated, safe in children and it has been used in this population in the US without severe adverse effects.
详细描述
CIPA patient do have very low or undetectable levels of norepinephrine in plasma and also have significant cognitive and behavioral problems. The aim of this project is to increase NE levels in brain and evaluate if this increase improve cognitive cognition or behavior.
Both drugs from the study have never been used in CIPA patients before, it is therefore very important to evaluate safety and tolerability of L-DOPS and carbidopa in this population.
Even if NE levels are very low in plasma of CIPA subjects, it is not know if NE levels are also low in central nervous system. It is very likely that this is also the case, however, levels of NE in brain will be checked in one CIPA subject as a prof of concept.
Study overview: Patients with CIPA will be screened and enrolled (visit 1) into part 1 of the pilot trial. Safety parameters including, adverse events, blood chemistries for renal and liver function testing, 12 lead electrocardiogram, temperature, weight and blood pressure (supine, seated and standing), non-verbal intelligence and behavior test, 24 hour urinary catecholamine excretion and plasma dopamine levels will be measured at baseline.
The patients will enter an open-label dose titration phase (visit 2a,b,c,d,e,f) during which adverse events will be continuously monitored. After reaching a dose the 100 mg/day dose, patients will be questioned about adverse events and have their blood pressure (supine, sitting and standing) measured. If no adverse events or abnormalities are detected patients will continue the dose titration. Safety assessments will be repeated and safety bloods obtained when the patient reaches the maximum tolerated dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female 15 years old or older
- •Patient carrying the genetic mutation for the NTRK1 gene
- •Patients (or guardian if patient it is underage) have signed a written consent to participate in the study after being fully informed about the procedure of the study and their right to withdraw at anytime during it.
排除标准
- •Patients taking amphetamines, norepinephrine reuptake inhibitors.
- •Patients taking any medication that can interact with the study drug L- DOPS.
- •Patients with previous severe hypertension (systolic blood pressure >170 mmHg)
- •Patients with arrhythmias or any other cardiac condition.
- •Women who are pregnant or breast feeding
- •Have a renal or hepatic disease
研究组 & 干预措施
Droxidopa First, Placebo Second
Participants in this arm will receive droxidopa first, then cross over and receive placebo
干预措施: Droxidopa (L-DOPS) (Drug)
Droxidopa First, Placebo Second
Participants in this arm will receive droxidopa first, then cross over and receive placebo
干预措施: Placebo (Drug)
Placebo First, Droxidopa Second
Participants in this arm will receive placebo first, then cross over and receive droxidopa
干预措施: Droxidopa (L-DOPS) (Drug)
Placebo First, Droxidopa Second
Participants in this arm will receive placebo first, then cross over and receive droxidopa
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events
时间窗: 8 weeks
Safety and tolerability will be assessed using general physical and neurological examinations, vital signs including blood pressure and heart rate, temperature and body weight, blood chemistries including serum creatinine, electrolytes, transaminases and liver function tests, 12 lead electrocardiograms and adverse events monitoring.
次要结局
未报告次要终点