Monocentric, Prospective Study to Assess the Pharmacokinetic Profile of Continuous and Diurnal Subcutaneous Apomorphine Infusion in Patients With Parkinson's Disease

Parkinson Disease Clinical Trial

— PHARM-APO  

Official title:

Pharmacokinetic Study of Continuous and Diurnal Subcutaneous Apomorphine Infusion in Patients With Parkinson's Disease Under Stabilized Treatment.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04887467
• Other study ID #: 35RC21_9909_PHARM-APO
• Status: Recruiting
• Phase: Phase 4
• Start date: September 16, 2021
• Est. completion date: September 16, 2024

Study information

• Verified date: April 2024
• Source: Rennes University Hospital
• Contact: Marc Verin, MD, PhD
• Phone: +33299289842
• Email: marc.verin[@]chu-rennes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 16, 2024
• Est. primary completion date: September 16, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 50 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Apomorphine
Assigned Interventions: blood sampling blood collection systolic, diastolic, mean blood pressure and heart rate measure

Locations

Country	Name	City	State
France	CHU Pontchaillou	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the curve of plasma apomorphine concentration between 0h and 24h		up to 24 hours
Secondary	Systolic blood pressure variations measured prior to each blood collection		up to 24 hours
Secondary	Diastolic blood pressure variations measured prior to each blood collection		up to 24 hours
Secondary	Mean blood pressure variations measured prior to each blood collection		up to 24 hours
Secondary	Heart rate variations measured prior to each blood collection		up to 24 hours
Secondary	Area under the curve of plasma apomorphine concentration - time values curve from treatment administration (t0) until 6h after (AUC0-6)		up to 24 hours
Secondary	Half-life (t1/2) determined by the t1/2 = Ln2/?z formula		up to 24 hours
Secondary	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)/?z wherein F is the absolute bioavailability		up to 24 hours
Secondary	Study of weight on area under the curve of drug concentrations		up to 24 hours
Secondary	Study of liver function on area under the curve of drug concentrations		up to 24 hours
Secondary	Study of the main genes involved in the biotransformation and transport of apomorphine	DNA bank	up to 24 hours
Secondary	Study of the pump type on area under the curve of drug concentrations		up to 24 hours