Apomorphine Pump in Early Stage of Parkinson’s Disease

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2016-002454-20-FR
• Date of registration: 16/03/2017
• Prospective Registration: No
• Primary sponsor: CHU de Rennes
• Public title: Apomorphine Pump in Early Stage of Parkinson’s Disease
• Scientific title: Apomorphine Pump in Early Stage of Parkinson’s Disease - EARLY-PUMP
• Date of first enrolment: 17/10/2016
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002454-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Best Medical Treatment (BMT) Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France

Contacts

• Name: LEROYER
• Affiliation: CHU de Rennes

• Name: LEROYER
• Affiliation: CHU de Rennes

Key inclusion & exclusion criteria

Inclusion criteria:
- Adults aged = 65 years,
- Idiopathic PD (According to British Brain Bank Criteria) without any other known or suspected cause of Parkinsonism,
- Hoehn and Yahr stage = 2.5 in the best ON,
- Disease duration = 4 years,
- Presence of fluctuations and/or dyskinesia for no more than 3 years,
- One of the two following forms of impairment:
* Impairment in activities of daily living (MDS-UPDRS II>6) due to PD-symptoms despite medical treatment in the worst condition or
* Impairment of social and occupational functioning (measured with SOFAS) due to PD-symptoms despite medical treatment (51-80%),
- PDQ39 completed,
- Able to understand and remember the components of the study,
- Written informed consent,
- Patients covered with social insurance.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 192
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Dementia (MoCA score < 22),
- Major uncontrolled depression at the time of assessment (BDI > 25) or Bipolar disease
- Active Hallucinations or history of hallucinations in the past year
- Need for nursing care,
- Previous use of apomorphine pump treatment,
- History of respiratory depression
- History of deep brain stimulation or lesional surgery for PD or intrajejunal L-Dopa,
- Presence of severe freezing or clinically relevant postural instability leading to falls during the ON state,
-Symptomatic clinically relevant and medically uncontrolled orthostatic hypotension,
- Clinically relevant hepatic dysfunction (total bilirubin >2.0 mg/dL, ALT and AST >2 times the upper limit of normal)
- Clinically relevant renal dysfunction (serum creatinine >2.0 mg/dL),
- Pregnant and breastfeeding women,
- Hypersensitivity to apomorphine or any excipients of the medicinal product,
- Concomitant therapy or within 28 days prior to baseline with : alpha-methyl dopa, metoclopramide, reserpine, neuroleptics (except Clozapine) , methylphenidate, or amphetamine, intrajejunal Ldopa
- History or current drug or alcohol abuse or dependencies,
- Patients with a borderline QT interval corrected for heart rate according to Bazett’s formula (QTc) of >450 ms for male and >470 ms for female at screening or history of long QTsyndrome; or >450 ms absolute duration,
- Adults legally protected (under judicial protection, guardianship or supervision), persons deprived of their liberty.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Parkinson’s disease
MedDRA version: 19.1 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: APOKINON
Product Name: APOKINON
Pharmaceutical Form: Solution for infusion

Primary Outcome(s)

Main Objective: The primary objective of the trial is to investigate the impact on the QoL of the apomorphine pump (APO group) compared to conventional optimized oral therapy (Control group) in earlier stages of PD, when motor complications have just developed

Timepoint(s) of evaluation of this end point: 12 months' follow up

Primary end point(s): The primary endpoint of the study is the difference in the PDQ39 summary index between the baseline assessment and the assessment at 12 months’ follow up. The two treatment groups (APO vs Control) will be compared.

Secondary Objective: •To assess the impact on motor and non-motor impairment of the APO group vs Control group;
•To assess the impact on personal, social and professional functioning for the APO group vs Control group;
•To investigate the safety and tolerability of the apomorphine pump vs conventional optimized oral therapy.
•To determine apomorphine pump-related cost- effectiveness compared to conventional optimized oral treatment at 24 months from the French National Health Insurance perspective.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1 / 12 months' follow up
2 / 12 months' follow up
3 / 12 months' follow up
4 / 12 months' follow up
5 / 12 months' follow up
6 / 12 months' follow up
7 / 12 months' follow up
8 / 12 months' follow up
9 / 12 months' follow up
10 / 12 months' follow up
11 / 12 months' follow up
12 / 12 months' follow up
13 / 12 months' follow up
14 / 12 months' follow up
15 / 12 months' follow up
16/ 12 months' follow up
17 / 24 months' follow up

Secondary end point(s): 1- Patient Global Impression of Change (PGIC)
2- Neurologist Global Impression of change (CGI-I)
3- Change in Non-Motor Aspects of Experiences of Daily Living (MDS-UPDRS I)
4- Change in Motor Aspects of Experiences of Daily Living in “on” and “off” medication (MDS-UPDRS II)
5- Change in motor examination during “on” periods (MDS-UPDRS III)
6- Change in motor complications with MDS-UPDRS IV
7- Patient diaries:
? Change in the number of hours per day in the “best ON” state
? Change in the number of hours per day in ON with dyskinesia
? Change in the number of hours per day in OFF state
? Sleeping-hours per day
8- Change in Score of the Non-Motor Symptoms Scale for PD (NMSS)
9- Change in psychosocial functioning PD (SCOPA-PS)
10- Changes in mood and occurrence and characteristics of depressive symptoms (BDI)
11- Change in occurrence of anxiety (STAI-S)
12 -Change in Score of VAS
13- Change in cognitive function: Montreal Cognitive Assessment (MoCA); Free and cued selective reminding test (FCSRT), 10/36 Spatial Recall Test (SPART), Digit Symbol Modalities test (SDMT), Digit Span, Letter-Number Sequencing Test (OTMT), Color Word Interference Test (CWIT), Benton judgement of line orientation test, Clock drawing test, Boston naming test short version, and semantic verbal fluency constituting the overall neuropsychological evaluation
14- Change in apathy (Apathy Scale and short version of LARS)
15- Change in medication (L-DOPA equivalents)
16- The safety endpoints:
? Frequency and intensity of behavioral symptoms (Ardouin Scale)
? Frequency, type and severity of therapy-related adverse events
? Skin changes
? Full blood count
? Epworth Sleepiness Scale
17- - Incremental Cost-Effectiveness Ratio (ICER) at 24 months following inclusion defined as (Average costs in “APO group” – average costs in “Control group”) / (average QALYs in “APO group”-average QALYs in “Control group”) to determine the cost for one QALY gained in the “APO group” versus “Control group”.

Secondary ID(s)

35RC15_9724

Source(s) of Monetary Support

CHU de Rennes