Pharmacokinetic Study of Continuous and Diurnal Subcutaneous Apomorphine Infusion in Patients With Parkinson's Disease Under Stabilized Treatment.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Area under the curve of plasma apomorphine concentration between 0h and 24h
研究概览
简要总结
This monocentric and prospective trial aims firstly to assess the pharmacokinetic profile of continuous and diurnal subcutaneous apomorphine infusion in patients with Parkinson's disease under stabilized treatment and, secondly, to collect data highlighting the possible influence of pharmacogenetics.
详细描述
A screening visit will be conducted 15 days to 2 months prior to the patient's hospitalization. Each subject will undergo a clinical examination including a collection of data relating to medical and surgical history, specific data related to Parkinson's disease and apomorphine pump treatment, and the completion of all items of the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) 3 scale in ON condition. Verification of the biological parameters necessary for the proper conduct of a pharmacokinetic study will also be carried out (venous capital; search for possible hepatic and/or renal failure).
The subjects will be called to the hospital two by two at 4:00 pm for a medical visit, during which a clinical examination will be performed (height, weight, fat mass, occurrence of infectious and/or inflammatory episodes) The subjects will then be placed in a room. A catheter will be placed in a forearm vein to allow blood sampling. All plasma samples will be taken from subjects who have been supine for at least 30 minutes. Blood pressure and heart rate will be checked before each sample.
A first blood sample will be taken at 8 pm followed by a standardized dinner. After the pump is stopped and removed at the patient's usual time, consecutive blood samples will be taken at T30, T60, T120, and T180 (i.e., 30 min, 1 h, 2 h, and 3 h after pump removal). The next morning, a new blood sample will be taken 10 min before the pump is turned on, at the usual time. A standardized breakfast will be served. A new series of consecutive blood samples will be taken at T30, T60, T120 and T180, following the same pattern as before.
A standardized lunch will be served around 11:30 am, and the patients will be allowed to leave after medical advice, at the latest at 2 pm.
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
- 50 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •50 to 70 year-old males
- •Suffering from Parkinson's disease, considered to be well controlled by treatment, including apomorphine (CGI criteria)
- •Use of daytime apomorphine pump treatment (nighttime discontinuation) for a minimum of 6 months, with a good tolerance and treatment dosage unchanged for a minimum of 3 months (apomorphine flow rate and daily dose and oral concomitant antiparkinsonian medication if applicable)
- •Autonomous patient in the apomorphine pump daily management (start and removal)
- •Written informed consent
- •Restrictive criteria to limit confounding factors : apomorphine type (Apokinon® apomorphine, cartridge or ampoule, Aguettant pharmaceutical laboratory) and medical device (Microjet CRONO-PAR pump (N=10) and France Développement Electronique (FDE) So Connect pump (N=10))
排除标准
- •Concomitant participation in a clinical trial that may affect the biological and/or pharmacokinetic parameters
- •Clinically relevant hepatic dysfunction that may significantly alter drug metabolism (value >2 times the upper limit of normal)
- •Clinically relevant renal dysfunction that may significantly alter drug excretion (clearance < 30 mL/min (chronic renal failure))
- •Alcohol abuse (> 30 g pure alcohol per day*) or drug addiction
- •Current tobacco consumption ; for ex-smokers : stopping smoking for less than 1 month at the time of inclusion
- •Dementia or cognitive impairment considered clinically significant
- •Adults legally protected (under judicial protection, guardianship or supervision), persons deprived of their liberty
研究组 & 干预措施
Patients with Parkinson disease
Apomorphine 5mg/mL, solution for infusion, intraveinous use
干预措施: Apomorphine (Drug)
结局指标
主要结局
Area under the curve of plasma apomorphine concentration between 0h and 24h
时间窗: up to 24 hours
次要结局
- Study of the main genes involved in the biotransformation and transport of apomorphine(up to 24 hours)
- Systolic blood pressure variations measured prior to each blood collection(up to 24 hours)
- Diastolic blood pressure variations measured prior to each blood collection(up to 24 hours)
- Study of the pump type on area under the curve of drug concentrations(up to 24 hours)
- Area under the curve of plasma apomorphine concentration - time values curve from treatment administration (t0) until 6h after (AUC0-6)(up to 24 hours)
- Study of weight on area under the curve of drug concentrations(up to 24 hours)
- Mean blood pressure variations measured prior to each blood collection(up to 24 hours)
- Heart rate variations measured prior to each blood collection(up to 24 hours)
- Half-life (t1/2) determined by the t1/2 = Ln2/λz formula(up to 24 hours)
- Apparent total clearance (Cl/F) and apparent volume of distribution (Vd) calculated according to the formulas Cl/F = Dose/AUC0-24 et Vd = Cl(T)/λz wherein F is the absolute bioavailability(up to 24 hours)
- Study of liver function on area under the curve of drug concentrations(up to 24 hours)