Clinical trial NCT04887467: Monocentric, Prospective Study to Assess the Pharmacokinetic Profile of Continuous and Diurnal Subcutaneous Apomorphine Infusion in Patients With Parkinson's Disease
Official title: Pharmacokinetic Study of Continuous and Diurnal Subcutaneous Apomorphine Infusion in Patients With Parkinson's Disease Under Stabilized Treatment.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson Disease
Keywords: Apomorphine
Pharmacokinetics
Dopamine Agonists
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2021-05-14
Enrollment: 19
Sex: MALE
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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))

Exclusion Criteria:

* 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

Primary outcomes:
measure: Area under the curve of plasma apomorphine concentration between 0h and 24h
timeFrame: up to 24 hours
Secondary outcomes:
measure: Systolic blood pressure variations measured prior to each blood collection
timeFrame: up to 24 hours
measure: Diastolic blood pressure variations measured prior to each blood collection
timeFrame: up to 24 hours
measure: Mean blood pressure variations measured prior to each blood collection
timeFrame: up to 24 hours
measure: Heart rate variations measured prior to each blood collection
timeFrame: up to 24 hours
measure: Area under the curve of plasma apomorphine concentration - time values curve from treatment administration (t0) until 6h after (AUC0-6)
timeFrame: up to 24 hours
measure: Half-life (t1/2) determined by the t1/2 = Ln2/λz formula
timeFrame: up to 24 hours
measure: 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
timeFrame: up to 24 hours
measure: Study of weight on area under the curve of drug concentrations
timeFrame: up to 24 hours
measure: Study of liver function on area under the curve of drug concentrations
timeFrame: up to 24 hours
measure: Study of the main genes involved in the biotransformation and transport of apomorphine
timeFrame: up to 24 hours
measure: Study of the pump type on area under the curve of drug concentrations
timeFrame: up to 24 hours
Other outcomes:
Locations:
city: Rennes
country: France
facility: CHU Pontchaillou
Study officials:
References: