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Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5-HydroxyTryptamine-2A (5HT2A) Inverse Agonist, to Treat Impulse Control Disorders in Parkinson's Disease. (PIMPARK)

Primary Purpose

Parkinson Disease

Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Active drug: pimavanserin 17mg (2 strength tablets)
Placebo: 2 tablets containing same excipients except active compound
Assessment of severity of ICD (impulse control disorders)
Assessment of motor and non-motors symptoms of PD Evaluation of hyper- and hypodopaminergic behaviors
Assessment of quality of life
Assessment of depression
Assessment of cognition
Assessment of severity of Parkinson Disease
Blood analysis
Cardiac monitoring
Sponsored by
University Hospital, Strasbourg, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring impulse control disorders, pimavanserin, Serotoninergic 5-HT2A inverse agonist, Dopamine agonist, Behavior

Eligibility Criteria

35 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patient with PD according to the UKPDSBB criteria for at least 1 year before randomization
  2. Patient, man or woman, aged from 35 to 75 years old
  3. Patient with moderately severe ICD assessed by QUIP-RS (each item being rated 0-16) defined as:

    • a combined ICD total score (defined as the sum of the 4 ICD sub-scores (pathological gambling + buying + hypersexuality + eating)) superior or equal to 10 or,
    • at least one of the 4 ICD sub-scores in the following range:

      1. "pathological gambling" sub-score from 6 to 12 (included),
      2. "buying" sub-score from 8 to 12 (included),
      3. "hypersexuality" sub-score from 8 to 12 (included),
      4. "eating" sub-score from 7 to 12 (included) (Weintraub et al., 2012). The use of "lower" margins will guarantee that the patient experiences behavioral disturbances severe enough to justify pimavanserin treatment. On the other hand, the use of "upper" margins will guarantee that the patients included in the trial will not suffer from ICD severe enough to question ethically the use of placebo during the 8 weeks of the treatment. Eligibility of patients with QUIP-RS sub-scores above 12 will be assessed upon investigator's request by an adjudication committee composed by independent experts external to the study (cf IX.3 Adjudication Committee).
  4. ICD onset after PD onset and after initiation of dopaminergic drugs
  5. Patient treated by dopaminergic drugs for at least 3 months before randomization
  6. Patient treated with a stable regimen of levodopa, dopamine agonists, COMT and MAOB inhibitors, amantadine, anticholinergic, antidepressant and benzodiazepine for at least 1 month before the randomization and be willing to remain on the same doses throughout the course of their participation in the trial (Papay et al., 2014)
  7. Patient with health insurance
  8. Patient/ guardian / curator who sign the written informed consent
  9. For women of childbearing potential, use of an effective contraception method* for at least 1 month prior to randomization until 8 weeks after the last dose of study drug administration. Women who do not have an effective contraception* must : have had her last natural menstruation ≥24 months prior to the selection visit, or have been surgically sterilized prior to the selection visit, or have had a hysterectomy prior to the selection visit.

Exclusion Criteria:

  1. Patient suffering from another parkinsonian syndrome (multiple system atrophy, progressive supranuclear palsy, Lewy body dementia, corticobasal degeneration)
  2. Patient who have a known hypersensitivity to the study treatment, based on known allergies to drugs of the same class
  3. Stroke, uncontrolled serious medical illness, myocardial infarction, congestive heart failure, cardiac function disorders, within 6 months before randomization
  4. Patient with history of long QT syndrome
  5. Patient with long QTcB detected with ECG at inclusion visit (> 450 ms)
  6. Patient treated with antipsychotic drugs during the last three months before randomization
  7. Patient treated with concomitant medication leading to torsade de pointes (TdP) without discontinuation ≥ 5 half-lives before randomization (please refer to medications list with known risks of TdP on appendix XVII.5.10 and check website https://crediblemeds.org/index.php/tools/ for the most up-to-date information)
  8. Patient with hydro-electrolytics troubles, particularly hypokaliemia or hypocalcemia not corrected, at inclusion visit or assessed no later than 8 days before randomization
  9. Patient treated with a strong or moderate CYP3A4 inducer: carbamazepine, rifampicin, phenytoin, modafinil, efavirenz or a strong inhibitor of CYP3A4: azole antifungals, protease inhibitors, macrolids, without discontinuation ≥ 5 half-lives before randomization
  10. Patient treated with medicinal plants interacting with CYP3A4 without discontinuation ≥ 5 half-lives before randomization (Echinacea (E.pupurea, E.angustifolia and E.pallida), Piperina, Artemisia, St. John's Wort and Ginkgo
  11. Patient with Montreal Cognitive Assessment (MoCA) (Nasreddine et al., 2005) score < 20 (to exclude patients likely with dementia) at inclusion visit (Papay et al., 2014).
  12. Patient suffering from severe depression or marked suicidal thoughts (score > 3 on the suicidal thoughts item of the MADRS) at inclusion visit (Papay et al., 2014)
  13. History of DBS within the past year before randomization, or change in stimulation parameters less than one month prior to randomization
  14. Hematologic or solid malignancy diagnosis within 5 years prior to randomization.

    [Note: Subjects with a history of localized skin cancer, basal cell or squamous cell carcinoma, may be enrolled in the study as long as they are cancer free prior to randomization. Subjects with other localized cancers (without metastatic spread) who have previously completed their course of treatment more than 5 years prior to randomization, are not currently receiving treatment and have been in remission may be enrolled only if, in the opinion of the Investigator, there is no expectation for recurrence or further cancer treatment during the study period. Antihormonal therapy (e.g., tamoxifen) is allowed if the subject's cancer is in remission and the subject is on stable maintenance therapy to reduce their risk of recurrence.]

  15. Patient suffering from severe renal impairment define as CrCL<30 mL/min, Cockcroft-Gault at inclusion visit or assessed no later than 8 days before randomization
  16. Clinically significant hepatic impairment
  17. Current participation in another research involving human beings of category 1 or 2
  18. Patient with language barriers precluding adequate understanding or co-operation or who, in the opinion of the investigator, should not participate in the trial
  19. Treatment with an investigational treatment within 30 days prior to randomization
  20. Woman pregnant, nursing or of childbearing potential age without effective contraception methods* or intends to become pregnant.

    • an effective contraception method is defined as implants, oral oestro-progestative contraceptives or progestative which inhibit ovulation contraceptives (e.g, desogestrel), or double barrier method (condom plus spermicide or diaphragm plus spermicide) or levonorgestrel intrauterine devices, or vasectomized partner (confirmed with two negative spermograms).

Sites / Locations

  • Service de Neurologie -CHU BesançonRecruiting
  • SERVICE DE NEUROLOGIE C, Unité mouvement anormaux/Centre expert Parkinson, CHU de Lyon, Hopital neurologique Pierre WertheimerRecruiting
  • SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson CHU Clermont-Ferrand, Hopital Gabriel MontpiedRecruiting
  • SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, Hopital Henri MondorRecruiting
  • SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Grenoble AlpesRecruiting
  • SERVICE DE NEUROLOGIE, Unité Mouvement Anormaux/Centre expert Parkinson, CHU de Lille, Hopital Roger SalengroRecruiting
  • SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de LimogesRecruiting
  • SERVICE DE NEUROLOGIE, Unité Mouvement Anormaux/Centre expert Parkinson, Hopital de la TimoneRecruiting
  • SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CIC, CHU de Nantes, Hopital LaennecRecruiting
  • SERVICE DE NEUROLOGIE Centre Expert Parkinson Hopital de la Pitié-SalpêtrièreRecruiting
  • Centre d'Inverstigation Clinique, CHU de PoitiersRecruiting
  • SERVICE DE NEUROLOGIE, CHU de REIMSRecruiting
  • SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Rennes, Hopital PontchaillouRecruiting
  • SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Rouen, Hopital Charles NicolleRecruiting
  • SERVICE DE NEUROLOGIE Unité de Mouvements Anormaux/Centre expert Parkinson, CHU de Strasbourg, Hopital de HautepierreRecruiting
  • SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CIC, CHU de Toulouse, Hopital Pierre-Paul RiquetRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

PIMAVANSERIN

PLACEBO

Arm Description

In this arm, each patient will take orally, once daily 2 tablets of active drug pimavanserin of 17mg each and this during the 8-weeks treatment period.

In this arm, each patient will take orally, once daily, 2 tablets of matching placebo (containing all of the same excipients except for the active compound) and this during the 8-weeks treatment period.

Outcomes

Primary Outcome Measures

Change in ICD (Impulsive Control Disorders) severity after 8 weeks of treatment evaluated by QUestionnaire for Impulse-compulsive disorder in Parkinson's disease Rating Scale (QUIP-RS).
The primary endpoint of this study will be assessed in both arms using the total form of QUIP-RS. QUIP-RS has 4 primary questions (pertaining to commonly reported thoughts, urges/desires, and behaviors associated with ICDs), each applied to the 4 ICDs (compulsive gambling, buying, eating, and sexual behavior) and 3 related disorders (medication use, punding, and hobbyism). It uses a 5-point Likert scale (score 0-4 for each question) to gauge the frequency of behaviors. Scores for each ICD and related disorder range from 0 to 16 and the total QUIP-RS score for all ICDs and related disorders combined ranges from 0 to 112, with a higher score indicating greater severity (ie, frequency) of symptoms.

Secondary Outcome Measures

Change SCale for Outcomes in Parkinson's disease - Sleep (SCOPA-SLEEP) score after 4 and 8 weeks of treatment
The SCOPA-SLEEP is a specific Parkinson's disease rating scale for assessing nighttime sleep (NS) problems and daytime sleepiness (DS) in the past month. The NS subscale has 5 items, scored from 0 (not at all) to 3 (a lot). The DS subscale is composed of 6 items with response options ranging from 0 (never) to 3 (often) with a higher total score indicating greater severity of sleep problems.
Change SCale for Outcomes in Parkinson's disease - Sleep (Insomnia severity index) score after 4 and 8 weeks of treatment
Scale ranging from 0 to 28 with a higher total score indicating greater severity of sleep problems.
Change SCale for Outcomes in Parkinson's disease - Sleep (PDSS-2: Parkinson Disease Sleep Scale-2) score after 4 and 8 weeks of treatment
Scale ranging from 0 to 60 with a higher total score indicating greater severity of sleep problems.
Change in Movement Disorders Society-sponsored Unified Parkinson's Disease Rating scale (MDS-UPDRS) scores after 4 and 8 weeks of treatment
MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease. The MDS-UPDRS has four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. The four parts contains 64 items which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect). Negative changes from baseline values indicate improvement.
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores after 4 and 8 weeks of treatment
MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Each item yields a score of 0 to 6 and the overall score ranges from 0 to 60 with higher MADRS score indicating more severe depression.
Change in Ardouin's scale scores after 4 and 8 weeks of treatment
The Ardouin's scale is a validated instrument using a structured and standardised interview composed of 21 items specifically designed to assess mood and behaviour with a view to quantifying changes related to Parkinson's Disease, to dopaminergic medication, and to non-motor fluctuations. Each item is scored from 0 (absent) to 4 (severe).
Change in the rate of Clinical Global Impression Severity (CGIS) scale after 4, 8 and 16 weeks of treatment
Severity of PD will be assessed in both arms using CGIS scale: the CGI-S is a 7-point scale that requires the rating of the severity of the patient's illness at the time of assessment. Possible ratings are: 1: Normal, not at all ill; 2: Borderline mentally ill; 3: Mildly ill; 4: Moderately ill ; 5: Markedly ill; 6: Severely ill; 7: Among the most extremely ill patients
Change in ICD (Impulsive Control Disorders) severity after 4 weeks of treatment evaluated by QUIP-RS.
Global functioning and severity of the disease will be assessed in both arms by QUIP-RS has 4 primary questions each applied to the 4 ICDs and 3 related disorders It uses a 5-point Likert scale and a higher score indicating greater severity (ie, frequency) of symptoms.
Changes in quality of life measured by Parkinson's Disease Questionnaire (PDQ-39) scores after 4 and 8 weeks of treatment
Functioning and well-being of patients during the preceding month will be assessed in both arms by 39 questions of the self-administered Parkinson's Disease Questionnaire (PQD-39). Each question is scored from 0 (never) to 4 (always), the higher score indicating higher impact of illness in quality of life.
Change in Zarit scale scores after 4 and 8 weeks of treatment for caregivers
The burden of the patient's functional and behavioural worsening and to home care will be assessed to the caregiver in both arms by the Zarit Burden scale. It is composed of 22 items to measure the magnitude of the burden experienced by the caregiver. Each item is scored from 0 (never) to 4 (almost always). With a higher score indicating a greater load suffered by the caregiver.

Full Information

First Posted
May 7, 2019
Last Updated
May 9, 2023
Sponsor
University Hospital, Strasbourg, France
Collaborators
NS-PARK, EUCLID Clinical Trial Platform, F-CRIN
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1. Study Identification

Unique Protocol Identification Number
NCT03947216
Brief Title
Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5-HydroxyTryptamine-2A (5HT2A) Inverse Agonist, to Treat Impulse Control Disorders in Parkinson's Disease.
Acronym
PIMPARK
Official Title
Study of Pimavanserin Efficacy for the Treatment of Impulse Control Disorders in Parkinson's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 23, 2020 (Actual)
Primary Completion Date
October 23, 2024 (Anticipated)
Study Completion Date
December 23, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Strasbourg, France
Collaborators
NS-PARK, EUCLID Clinical Trial Platform, F-CRIN

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
There is no consensus on the treatment of Impulse Control Disorder (ICD) in Parkinson Disease (PD) though it is recommended to reduce the dosage of dopamine agonists (DA). Reduction of DA frequently leads to a worsening of motor signs (parkinsonism or dyskinesias due to the concomitant increase of levodopa doses) and non-motor signs with the appearance of a DA withdrawal syndrome (DAWS). Chronic stimulation of the sub-thalamic nuclei may reduce ICD but is restricted to a minority of patients and cases of new-onset ICD symptoms post stimulation have been reported. The benefit of amantadine in pathological gambling is controversial and the efficacy of clozapine has been reported in a few cases but with serious safety limitations. Very recently, naltrexone did not significantly improve ICD. Thus, an efficacious and safe treatment of ICD in PD remains an unmet need for clinical practice. Recently, it has been reported that pimavanserin, a selective serotonin 5-HT2A inverse agonist with a satisfactory safety profile without motor side effects, was efficient in improving psychosis, insomnia and day-time sleep in PD. Pimavanserin, marketed under the tradename NUPLAZID® was approved in 2016 by the U.S. Food and Drug Administration (FDA) for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. The link between serotonin and ICD has been well established, since the enhancement of 5HT2A receptors stimulation is associated to ICD, since serotonin modulates mesolimbic dopaminergic reward system transmission and given that serotonin neurotransmission is increased during chronic intake of dopamine agonist such as pramipexole which is well-known to induce ICD in PD patients. Thus, there is a large body of evidence suggesting that the decrease of the 5HT2A activity could be efficient in reducing ICD in PD. This further supports the concept of testing the efficacy of pimavanserin (a selective 5HT2A inverse agonist) for treating ICD in PD. Our aim is to conduct a study evaluating the efficacy and safety of pimavanserin on ICD in PD. This clinical trial is conducted with the support of the French NS-Park/FCRIN (French Clinical Research Infrastructure Network) network.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
Keywords
impulse control disorders, pimavanserin, Serotoninergic 5-HT2A inverse agonist, Dopamine agonist, Behavior

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PIMAVANSERIN
Arm Type
Experimental
Arm Description
In this arm, each patient will take orally, once daily 2 tablets of active drug pimavanserin of 17mg each and this during the 8-weeks treatment period.
Arm Title
PLACEBO
Arm Type
Placebo Comparator
Arm Description
In this arm, each patient will take orally, once daily, 2 tablets of matching placebo (containing all of the same excipients except for the active compound) and this during the 8-weeks treatment period.
Intervention Type
Drug
Intervention Name(s)
Active drug: pimavanserin 17mg (2 strength tablets)
Intervention Description
Pimavanserin 17mg (2 strength tablets) will be taken orally daily from day 1 to Visit 4 (Week 8)
Intervention Type
Drug
Intervention Name(s)
Placebo: 2 tablets containing same excipients except active compound
Intervention Description
Placebo (2 strength tablets) will be taken orally daily from day 1 to Visit 4 (Week 8)
Intervention Type
Behavioral
Intervention Name(s)
Assessment of severity of ICD (impulse control disorders)
Intervention Description
Questionnaire for impulsive-compulsive disorders in Parkinson's disease rating scale (QUIP-RS) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)
Intervention Type
Behavioral
Intervention Name(s)
Assessment of motor and non-motors symptoms of PD Evaluation of hyper- and hypodopaminergic behaviors
Intervention Description
Hyper- and hypodopaminergic behaviors (Ardouin's scale); Movement disorders society sponsored unified Parkinson's disease rating scale (MDS-UPDR), and daytime and night time sleep by scale for outcomes in Parkinson's disease SLEEP (SCOPA-SLEEP, ISI, PDSS-2) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)
Intervention Type
Behavioral
Intervention Name(s)
Assessment of quality of life
Intervention Description
Parkinson's Disease questionnaire (PDQ-39) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)
Intervention Type
Behavioral
Intervention Name(s)
Assessment of depression
Intervention Description
Montgomery-Åsberg Depression Rating Scale (MADRS) will be administrated at day 0 and day 56 (week 8)
Intervention Type
Behavioral
Intervention Name(s)
Assessment of cognition
Intervention Description
Cognitive state of patients by Montreal Cognitive Assessment (MOCA) will be assessed at day 0.
Intervention Type
Behavioral
Intervention Name(s)
Assessment of severity of Parkinson Disease
Intervention Description
Clinical Global Impression Severity scale (CGIS) will be administrated at day 0 , day 7, day 14, day 28, day 42 and day 56 (week 8) and day 112 (Week 16)
Intervention Type
Procedure
Intervention Name(s)
Blood analysis
Intervention Description
Blood sample will be collected for analyse of safety (blood count/liver and kidney functions, electrolytes) at day 0 and day 56
Intervention Type
Procedure
Intervention Name(s)
Cardiac monitoring
Intervention Description
Electrocardiogram will be realized at day 0, 28 and 56.
Primary Outcome Measure Information:
Title
Change in ICD (Impulsive Control Disorders) severity after 8 weeks of treatment evaluated by QUestionnaire for Impulse-compulsive disorder in Parkinson's disease Rating Scale (QUIP-RS).
Description
The primary endpoint of this study will be assessed in both arms using the total form of QUIP-RS. QUIP-RS has 4 primary questions (pertaining to commonly reported thoughts, urges/desires, and behaviors associated with ICDs), each applied to the 4 ICDs (compulsive gambling, buying, eating, and sexual behavior) and 3 related disorders (medication use, punding, and hobbyism). It uses a 5-point Likert scale (score 0-4 for each question) to gauge the frequency of behaviors. Scores for each ICD and related disorder range from 0 to 16 and the total QUIP-RS score for all ICDs and related disorders combined ranges from 0 to 112, with a higher score indicating greater severity (ie, frequency) of symptoms.
Time Frame
at day 0 and week 8
Secondary Outcome Measure Information:
Title
Change SCale for Outcomes in Parkinson's disease - Sleep (SCOPA-SLEEP) score after 4 and 8 weeks of treatment
Description
The SCOPA-SLEEP is a specific Parkinson's disease rating scale for assessing nighttime sleep (NS) problems and daytime sleepiness (DS) in the past month. The NS subscale has 5 items, scored from 0 (not at all) to 3 (a lot). The DS subscale is composed of 6 items with response options ranging from 0 (never) to 3 (often) with a higher total score indicating greater severity of sleep problems.
Time Frame
At day 0, week 4 and week 8
Title
Change SCale for Outcomes in Parkinson's disease - Sleep (Insomnia severity index) score after 4 and 8 weeks of treatment
Description
Scale ranging from 0 to 28 with a higher total score indicating greater severity of sleep problems.
Time Frame
At day 0, week 4 and week 8
Title
Change SCale for Outcomes in Parkinson's disease - Sleep (PDSS-2: Parkinson Disease Sleep Scale-2) score after 4 and 8 weeks of treatment
Description
Scale ranging from 0 to 60 with a higher total score indicating greater severity of sleep problems.
Time Frame
At day 0, week 4 and week 8
Title
Change in Movement Disorders Society-sponsored Unified Parkinson's Disease Rating scale (MDS-UPDRS) scores after 4 and 8 weeks of treatment
Description
MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease. The MDS-UPDRS has four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. The four parts contains 64 items which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect). Negative changes from baseline values indicate improvement.
Time Frame
At day 0, week 4 and week 8
Title
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores after 4 and 8 weeks of treatment
Description
MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Each item yields a score of 0 to 6 and the overall score ranges from 0 to 60 with higher MADRS score indicating more severe depression.
Time Frame
At day 0, week 4 and week 8
Title
Change in Ardouin's scale scores after 4 and 8 weeks of treatment
Description
The Ardouin's scale is a validated instrument using a structured and standardised interview composed of 21 items specifically designed to assess mood and behaviour with a view to quantifying changes related to Parkinson's Disease, to dopaminergic medication, and to non-motor fluctuations. Each item is scored from 0 (absent) to 4 (severe).
Time Frame
At day 0, week 4 and week 8
Title
Change in the rate of Clinical Global Impression Severity (CGIS) scale after 4, 8 and 16 weeks of treatment
Description
Severity of PD will be assessed in both arms using CGIS scale: the CGI-S is a 7-point scale that requires the rating of the severity of the patient's illness at the time of assessment. Possible ratings are: 1: Normal, not at all ill; 2: Borderline mentally ill; 3: Mildly ill; 4: Moderately ill ; 5: Markedly ill; 6: Severely ill; 7: Among the most extremely ill patients
Time Frame
At day 0, week 4, week 8 and week 16
Title
Change in ICD (Impulsive Control Disorders) severity after 4 weeks of treatment evaluated by QUIP-RS.
Description
Global functioning and severity of the disease will be assessed in both arms by QUIP-RS has 4 primary questions each applied to the 4 ICDs and 3 related disorders It uses a 5-point Likert scale and a higher score indicating greater severity (ie, frequency) of symptoms.
Time Frame
At day 0 and week 4
Title
Changes in quality of life measured by Parkinson's Disease Questionnaire (PDQ-39) scores after 4 and 8 weeks of treatment
Description
Functioning and well-being of patients during the preceding month will be assessed in both arms by 39 questions of the self-administered Parkinson's Disease Questionnaire (PQD-39). Each question is scored from 0 (never) to 4 (always), the higher score indicating higher impact of illness in quality of life.
Time Frame
At day 0, week 4 and week 8
Title
Change in Zarit scale scores after 4 and 8 weeks of treatment for caregivers
Description
The burden of the patient's functional and behavioural worsening and to home care will be assessed to the caregiver in both arms by the Zarit Burden scale. It is composed of 22 items to measure the magnitude of the burden experienced by the caregiver. Each item is scored from 0 (never) to 4 (almost always). With a higher score indicating a greater load suffered by the caregiver.
Time Frame
At day 0, week 4 and week 8
Other Pre-specified Outcome Measures:
Title
Total number of adverse events and serious adverse events
Description
Open-ended questionnaire will be used in both arms
Time Frame
At week 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient with PD according to the UKPDSBB criteria for at least 1 year before randomization Patient, man or woman, aged from 35 to 75 years old Patient with moderately severe ICD assessed by QUIP-RS (each item being rated 0-16) defined as: a combined ICD total score (defined as the sum of the 4 ICD sub-scores (pathological gambling + buying + hypersexuality + eating)) superior or equal to 10 or, at least one of the 4 ICD sub-scores in the following range: "pathological gambling" sub-score from 6 to 12 (included), "buying" sub-score from 8 to 12 (included), "hypersexuality" sub-score from 8 to 12 (included), "eating" sub-score from 7 to 12 (included) (Weintraub et al., 2012). The use of "lower" margins will guarantee that the patient experiences behavioral disturbances severe enough to justify pimavanserin treatment. On the other hand, the use of "upper" margins will guarantee that the patients included in the trial will not suffer from ICD severe enough to question ethically the use of placebo during the 8 weeks of the treatment. Eligibility of patients with QUIP-RS sub-scores above 12 will be assessed upon investigator's request by an adjudication committee composed by independent experts external to the study (cf IX.3 Adjudication Committee). ICD onset after PD onset and after initiation of dopaminergic drugs Patient treated by dopaminergic drugs for at least 3 months before randomization Patient treated with a stable regimen of levodopa, dopamine agonists, COMT and MAOB inhibitors, amantadine, anticholinergic, antidepressant and benzodiazepine for at least 1 month before the randomization and be willing to remain on the same doses throughout the course of their participation in the trial (Papay et al., 2014) Patient with health insurance Patient/ guardian / curator who sign the written informed consent For women of childbearing potential, use of an effective contraception method* for at least 1 month prior to randomization until 8 weeks after the last dose of study drug administration. Women who do not have an effective contraception* must : have had her last natural menstruation ≥24 months prior to the selection visit, or have been surgically sterilized prior to the selection visit, or have had a hysterectomy prior to the selection visit. Exclusion Criteria: Patient suffering from another parkinsonian syndrome (multiple system atrophy, progressive supranuclear palsy, Lewy body dementia, corticobasal degeneration) Patient who have a known hypersensitivity to the study treatment, based on known allergies to drugs of the same class Stroke, uncontrolled serious medical illness, myocardial infarction, congestive heart failure, cardiac function disorders, within 6 months before randomization Patient with history of long QT syndrome Patient with long QTcB detected with ECG at inclusion visit (> 450 ms) Patient treated with antipsychotic drugs during the last three months before randomization Patient treated with concomitant medication leading to torsade de pointes (TdP) without discontinuation ≥ 5 half-lives before randomization (please refer to medications list with known risks of TdP on appendix XVII.5.10 and check website https://crediblemeds.org/index.php/tools/ for the most up-to-date information) Patient with hydro-electrolytics troubles, particularly hypokaliemia or hypocalcemia not corrected, at inclusion visit or assessed no later than 8 days before randomization. To be eligible, the patient's electrolyte values should be within the following limits: 3.5 ≤ K+ ≤ 5 mmol/L 135 ≤ Na+ ≤ 145 mmol/L 2,20 ≤ Ca2+ ≤ 2,60 mmol/L Patient treated with a strong or moderate CYP3A4 inducer: carbamazepine, rifampicin, phenytoin, modafinil, efavirenz or a strong inhibitor of CYP3A4: azole antifungals, protease inhibitors, macrolids, without discontinuation ≥ 5 half-lives before randomization Patient treated with medicinal plants interacting with CYP3A4 without discontinuation ≥ 5 half-lives before randomization (Echinacea (E.pupurea, E.angustifolia and E.pallida), Piperina, Artemisia, St. John's Wort and Ginkgo Patient with Montreal Cognitive Assessment (MoCA) (Nasreddine et al., 2005) score < 20 (to exclude patients likely with dementia) at inclusion visit (Papay et al., 2014). Patient suffering from severe depression or marked suicidal thoughts (score > 3 on the suicidal thoughts item of the MADRS) at inclusion visit (Papay et al., 2014) History of DBS within the past year before randomization, or change in stimulation parameters less than one month prior to randomization Hematologic or solid malignancy diagnosis within 5 years prior to randomization. [Note: Subjects with a history of localized skin cancer, basal cell or squamous cell carcinoma, may be enrolled in the study as long as they are cancer free prior to randomization. Subjects with other localized cancers (without metastatic spread) who have previously completed their course of treatment more than 5 years prior to randomization, are not currently receiving treatment and have been in remission may be enrolled only if, in the opinion of the Investigator, there is no expectation for recurrence or further cancer treatment during the study period. Antihormonal therapy (e.g., tamoxifen) is allowed if the subject's cancer is in remission and the subject is on stable maintenance therapy to reduce their risk of recurrence.] Patient suffering from severe renal impairment define as CrCL<30 mL/min, Cockcroft-Gault at inclusion visit or assessed no later than 8 days before randomization Clinically significant hepatic impairment Concurrent participation in another research involving a drug or medical device Patient with language barriers precluding adequate understanding or co-operation or who, in the opinion of the investigator, should not participate in the trial Treatment with an investigational treatment within 30 days prior to randomization Woman pregnant, nursing or of childbearing potential age without effective contraception methods* or intends to become pregnant. an effective contraception method is defined as implants, oral oestro-progestative contraceptives or progestative which inhibit ovulation contraceptives (e.g, desogestrel), or double barrier method (condom plus spermicide or diaphragm plus spermicide) or levonorgestrel intrauterine devices, or vasectomized partner (confirmed with two negative spermograms).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mathieu ANHEIM, MD
Phone
+33 3 88 12 85 35
Email
mathieu.anheim@chru-strasbourg.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Olivier RASCOL, MD
Phone
+33 5 61 14 59 62
Email
olivier.rascol@univ-tlse3.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mathieu ANHEIM, MD
Organizational Affiliation
CHRU Strasbourg
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service de Neurologie -CHU Besançon
City
Besançon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthieu BEREAU, MD
Phone
+33 3 81 66 86 55
Email
mbereau@chu-besancon.fr
First Name & Middle Initial & Last Name & Degree
Matthieu BEREAU, MD
Facility Name
SERVICE DE NEUROLOGIE C, Unité mouvement anormaux/Centre expert Parkinson, CHU de Lyon, Hopital neurologique Pierre Wertheimer
City
Bron
ZIP/Postal Code
69677
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chloé LAURENCIN, MD
Phone
33 4 72 35 72 35
Email
chloe.laurencin@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Chloé LAURENCIN, MD
Facility Name
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson CHU Clermont-Ferrand, Hopital Gabriel Montpied
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ana MARQUES, MD
Phone
33 4 73 75 22 00
Email
ar_marques@chu-clermontferrand.fr
First Name & Middle Initial & Last Name & Degree
Ana MARQUES, MD
Facility Name
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, Hopital Henri Mondor
City
Créteil
ZIP/Postal Code
94010
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe REMY, MD
Phone
+33 1 49 81 43 53
Email
neuro-philippe.remy@hmn.aphp.fr
First Name & Middle Initial & Last Name & Degree
Philippe REMY, MD
Facility Name
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Grenoble Alpes
City
Grenoble
ZIP/Postal Code
38043
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valérie FRAIX, MD
Phone
+33 4 76 76 94 52
Email
vfraix@chu-grenoble.fr
First Name & Middle Initial & Last Name & Degree
Valérie FRAIX, MD
Facility Name
SERVICE DE NEUROLOGIE, Unité Mouvement Anormaux/Centre expert Parkinson, CHU de Lille, Hopital Roger Salengro
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luc DEFEBVRE, MD
Phone
+33 3 20 44 67 30
Email
Luc.DEFEBVRE@CHRU-LILLE.FR
First Name & Middle Initial & Last Name & Degree
Luc DEFEBVRE, MD
Facility Name
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean Luc HOUETO, MD
Phone
+33 5 55 05 65 60
Email
jean-luc.houeto@chu-limoges.fr
First Name & Middle Initial & Last Name & Degree
Jean-Luc HOUETO, MD
Facility Name
SERVICE DE NEUROLOGIE, Unité Mouvement Anormaux/Centre expert Parkinson, Hopital de la Timone
City
Marseille
ZIP/Postal Code
13385
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Philippe AZULAY, MD
Phone
+33 4 91 38 43 33
Email
Jean-philippe.AZULAY@ap-hm.fr
First Name & Middle Initial & Last Name & Degree
Jean-Philippe AZULAY, MD
Facility Name
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CIC, CHU de Nantes, Hopital Laennec
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tiphaine ROUAUD, MD
Phone
+33 2 40 16 52 86
Email
Tiphaine.Rouaud@chu-nantes.fr
First Name & Middle Initial & Last Name & Degree
Tiphaine ROUAUD, MD
Facility Name
SERVICE DE NEUROLOGIE Centre Expert Parkinson Hopital de la Pitié-Salpêtrière
City
Paris
ZIP/Postal Code
75651
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Christophe CORVOL, MD
Phone
+33 1 42 16 57 66
Email
jean-christophe.corvol@aphp.fr
First Name & Middle Initial & Last Name & Degree
Jean-Christophe CORVOL, MD
Facility Name
Centre d'Inverstigation Clinique, CHU de Poitiers
City
Poitiers
ZIP/Postal Code
86021
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Isabelle BENATRU, MD
Phone
+33 5 49 44 44 46
Email
isabelle.benatru@chu-poitiers.fr
First Name & Middle Initial & Last Name & Degree
Isabelle BENATRU, MD
Facility Name
SERVICE DE NEUROLOGIE, CHU de REIMS
City
Reims
ZIP/Postal Code
51100
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne DOE DE MAINDREVILLE, MD
Email
adoedemaindreville@chu-reims.fr
First Name & Middle Initial & Last Name & Degree
Anne DOE DE MAINDREVILLE, MD
Facility Name
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Rennes, Hopital Pontchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sophie DRAPIER, MD
Phone
+33 2 99 28 42 93
Email
Sophie.Drapier@chu-rennes.fr
First Name & Middle Initial & Last Name & Degree
Sophie DRAPIER, MD
Facility Name
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Rouen, Hopital Charles Nicolle
City
Rouen
ZIP/Postal Code
76031
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David MALTETE, MD
Phone
+33 2 32 88 87 40
Email
david.maltete@chu-rouen.fr
First Name & Middle Initial & Last Name & Degree
David MALTETE, MD
Facility Name
SERVICE DE NEUROLOGIE Unité de Mouvements Anormaux/Centre expert Parkinson, CHU de Strasbourg, Hopital de Hautepierre
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mathieu ANHEIM, MD
Phone
+33 3 88 12 85 35
Email
mathieu.anheim@chru-strasbourg.fr
First Name & Middle Initial & Last Name & Degree
Mathieu ANHEIM, MD
Facility Name
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CIC, CHU de Toulouse, Hopital Pierre-Paul Riquet
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivier RASCOL, MD
Phone
+33 5 61 14 59 62
Email
olivier.rascol@univ-tlse3.fr
First Name & Middle Initial & Last Name & Degree
Olivier RASCOL, MD

12. IPD Sharing Statement

Learn more about this trial

Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5-HydroxyTryptamine-2A (5HT2A) Inverse Agonist, to Treat Impulse Control Disorders in Parkinson's Disease.

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