Investigation of the effect of Nabilon in patients suffering from Parkinson´s Disease with non-Motor symptoms (e.g.sleeping dirsorders, cognitive dysfunction, hallucinations, autonomic dysfunction,...)

• Register: EUCTR
• Last refreshed on: 11 March 2020
• Main ID: EUCTR2017-004253-16-AT
• Date of registration: 27/02/2018
• Prospective Registration: Yes
• Primary sponsor: Medizinische Universität Innsbruck, Universitätsklinik für Neurologie
• Public title: Investigation of the effect of Nabilon in patients suffering from Parkinson´s Disease with non-Motor symptoms (e.g.sleeping dirsorders, cognitive dysfunction, hallucinations, autonomic dysfunction,...)
• Scientific title: Nabilone for non-motor symptoms in Parkinson’s disease: An open-label study to evaluate long-term safety and efficacy
• Date of first enrolment: 13/04/2018
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004253-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria

Contacts

• Name: Clinical Trial Center Neurology
• Affiliation: Medizinische Universität Innsbruck, Universitätsklinik für Neurologie

• Name: Clinical Trial Center Neurology
• Affiliation: Medizinische Universität Innsbruck, Universitätsklinik für Neurologie

Key inclusion & exclusion criteria

Inclusion criteria:
1. In order to be eligible for the study, patients must have completed the double-blind phase of the NMS-Nab trial as responders within the last 2 months.
2. For patients that completed NMS-Nab Study over 2 months prior to the Screening Visit, and meet all other inclusion criteria, eligibility should be discussed on a case-by-case basis.
3. Only patients without a drug-related SAE or moderate or severe AE during the NMS-Nab Study can be included in the study
4. Patients must be able and willing to provide written informed consent prior to any study related procedure being performed. Patients with a legal guardian should be consented according to local requirements.
5. Patients must be willing and able to take oral medication and able to comply with the study specific procedures.
6. The patient is in good health as determined by medical examination.

The inclusion criteria of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal trial were as follows:
1. age =30 years
2. diagnosis of PD (de novo or on stable medication without disturbing motor fluctuations or dyskinesia)
3. NMS with a score of =4 on MDS-UPDRS Part 1. One of the following domains have to be affected with a score =2: 1.4 (anxious mood) or 1.9 (pain)
4. On a stable regimen of anti-parkinson medications for at least 30 days prior to screening and willing to continue the same doses and regimens during study participation
5. Any other current and allowed prescription/non-prescription medications and/or nutritional supplements taken regularly must have been at a stable dose and regimen for at least 30 days prior to screening, and subject must be willing to continue the same doses and regimens during study participation
6. Signed a current IRB-approved informed consent form
7. Acceptable method of contraception

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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion criteria:
1. Patients that experienced a drug-related SAE or had a moderate or severe AE during the NMS-Nab Study will be excluded in the study.

The exclusion criteria of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal trial were as follows:
1. Previous participation in any study with nabilone
2. current use of cannabinoids or use within 30 days prior to screening
3. current or recent (within 30 days prior to screening) participation in another study with an investigational medicinal product
4. atypical or secondary parkinsonism
5. presence of motor complications if, based on the investigator’s judgment, not adequately controlled (i.e. a score =2 on one of the items of the MDS-UPDRS Part IV at screening)
6. Hoehn and Yahr stage ON > 3
7. Evidence of disturbing impulse control disorder
8. History of neurosurgical intervention for PD
9. Presence of clinically significant symptomatic orthostatic hypotension at screening (MDS-UPDRS 1.12 > 2)
10. Use of prohibited medication listed in 7.4.2
11. Laboratory values clinically significant out-of-range at screening or within 4 weeks prior to screening
12. Known or diagnosed sinus tachycardia in ECG evaluation at screening or within 4 weeks prior to screening
13. presence of an acute or chronic major psychiatric disorder (e.g., Major Depressive Disorder, psychosis) or symptom (e.g., hallucinations, agitation, paranoia) (MDS-UPDRS 1.2 and/or 1.3 > 2)
14. recent suicidal attempt within the past five years or suicidal ideation within the past 6 months
15. presence of dementia (MDS-UPDRS 1.1 > 2, MMSE of < 24 at screening)
16. clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation (based on the investigator’s judgment).
17. moderate or severe hepatic or renal impairment.
18. History of chronic alcohol or drug abuse within the last 2 years
19. women of child-bearing potential who do not practice an acceptable method of birth control [*Acceptable methods of birth control for women and men in this study are: surgical sterilization (e.g. tubal ligation for females), intrauterine devices that release hormones (hormone spiral), oral hormonal contraceptive, contraceptive patch, dermal hormonal contraception, vaginal hormonal contraception (NuvaRing®), implants that release progesterone (Implanon®), long-acting injectable contraceptive, partner’s vasectomy, a double-protection method, postmenopausal (> 2 year absence of vaginal bleeding).]
20. Pregnant women, or women planning to become pregnant during the course of the study, or nursing women.
21. Known hypersensitivity to any components of the IMP or excipients
22. Patient is legally incapacitated or persons held in an institution by legal or official order
23. Persons with any kind of dependency on the investigator or employed by the Sponsor or investigator



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

Health Condition(s) or Problem(s) studied

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

Subject with non-Motor symptoms of Parkinson´s disease
MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Nabilone
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NABILONE
CAS Number: 51022-71-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-

Primary Outcome(s)

Main Objective: The primary objective of this study is to evaluate long-term safety and tolerability of nabilone in PD patients.

Timepoint(s) of evaluation of this end point: The primary safety analysis will be performed with the safety data set including all patients with the intake of at least one study drug and performing at least V 1. A safety analysis will be performed on all events and tolerability issues, as well as the hallucination item, orthostatic hypotension item, the day-time sleepiness item of Part I of MDS-UPDRS, and C-SSRS occurring through the overall course of the study.

Primary end point(s): Primary Safety and tolerability endpoints:
• Safety and tolerability will be evaluated with reference to the following:Number of subjects (%) who discontinue the study
• Number of subjects (%) who discontinue the study due to AE
• Adverse Events (AE)
• Physical and neurological examination findings
• Vital signs assessments
• Subjects compliance, prior and concomitant medication use
• Hallucination item (1.2) of Movement Disorders Society – Unified Parkinson´s Disease Rating Scale (MDS-UPDRS)
• Orthostatic hypotension (OH) item (1.12) of Movement Disorders Society – Unified Parkinson´s Disease Rating Scale (MDS-UPDRS)
• Day-time sleepiness item (1.8) of Movement Disorders Society – Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Suicidality using the Columbia-Suicide Severity Rating Scale (C-SSRS)

Secondary Objective: The secondary objectives of the study are to assess the effects of long-term, open-label dosing with nabilone on different symptoms of PD and quality of life in patients with PD.


The exploratory objective of this study will be an Eye-tracking evaluation in PD patients taking nabilone at Visit V 2 to examine the change of the reaction time, attention span, and concentrativeness.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The secondary efficacy criterion will be measured as the change of all assessments between V 1 and month 6, except for the MoCA and MMSE (will be compared between the Screening visit of the precursory NMS-Nab study and the Termination Visit of this study).



The exploratory end point will be measured at V 2 of this study and compared to the Screening and Termination Visit of the precursory NMS-Nab Study.

Secondary end point(s): Secondary Efficacy endpoints:
Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes from V 1 to the termination visit (V 4) in the following assessments:
• Total and different parts of MDS-UPDRS
• Different domains of MDS-UPDRS Part I
• NMSS
• HAD-S
• PDQ-8
• ESS
• FSS
• KPPS
• QUIP-RS
• CGI-I

The change of MMSE and MoCA score values between the Screening Visit of the NMS-Nab Study (before the first intake of nabilone medication) and the termination visit of this study will be assessed as secondary efficacy endpoints.


Exploratory Endpoints
The change of the reaction time, attention span, and concentrativeness between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study NMS-Nab and V 2 of this study as measured by the Eye-tracking examination will be an exploratory endpoint.

Secondary ID(s)

NMSNab2study

Source(s) of Monetary Support

AOP Orphan Pharmaceuticals AG

Ethics review

Status: Approved
Approval date: 07/02/2018
Contact: