Nabilone for Non-motor Symptoms in Parkinson's Disease

Study Overview
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Brief Summary
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This is an open-label extension study for participants of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal NMS-Nab Study, assessing the long-term safety and efficacy of nabilone for non-motor symptoms in patients with Parkinson´s Disease (PD). Nabilone is an analogue of tetrahydrocannabinol (THC), the psychoactive component of cannabis. Nabilone acts as a partial agonist on both Cannabinoid 1 (CB1) and Cannabinoid 2 (CB2) receptor in humans and therefore mimics the effect of THC but with more predictable side effects and less euphoria. Eligible patients will be re-tapered in an open-label nabilone dose optimization phase followed by an open-label period of 6 months on a stable nabilone dose.

Detailed Description
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This is an open-label extension study for participants of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal NMS-Nab Study, assessing the long-term safety and efficacy of nabilone for non-motor symptoms in patients with Parkinson´s Disease. Nabilone is an analogue of tetrahydrocannabinol (THC), the psychoactive component of cannabis. Eligible subjects will be re-tapered with open-label nabilone, optimally up to the dose the patient had in the NMS-Nab Trial. It is the investigator´s decision to modify this dose, if necessary. The re-tapering will be performed up to a maximum dose of 1 mg twice daily. Treatment responders will enter the open-label treatment period for 6 months with visits being performed every 3 months in the context of the patient´s regularly scheduled visits in the specialized outpatient department. The last visit will be the Termination Visit. Following this, nabilone will be tapered. During this period the patients will receive phone calls every other day. A Safety Follow-Up Visit will be performed.

Official Title
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Nabilone for Non-motor Symptoms in Parkinson's Disease: An Open-label Study to Evaluate Long-term Safety and Efficacy

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Nabilone 0.25 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to be eligible for participation in the study, subjects must meet all inclusion criteria: 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. For patients that completed NMS-Nab Study over 2 months prior to the Screening / Baseline Visit, and meet all other inclusion criteria, eligibility should be discussed on a case-by-case basis. Only patients without a drug-related serious adverse event (SAE) or (drug-related) moderate or severe AE during the NMS-Nab Study can be included in the study 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. Patients must be willing and able to take oral medication and able to comply with the study specific procedures. The patient is in good health as determined by medical examination and based on the investigator's judgement Exclusion Criteria: Patients with any of the following characteristics will be excluded from entering the study: Patients with PArkinson´s Disease (PD) who have not participated in the randomized double-blind phase of the previous NMS-Nab Study. Patients that experienced a drug-related SAE or had a (drug-related) moderate or severe AE during the NMS-Nab Study will be excluded in the study. Patients who are unable or unwilling to comply with the study procedures in the investigator´s opinion. Patients with any clinically significant or unstable medical or surgical condition at the Screening / Baseline Visit that may preclude safety and the completion of the study participation (based on the investigator's judgement).

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open-label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment Group<br>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg | Drug: Nabilone 0.25 mg<br>* capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis<br>* Other names: Canemes;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs in PD Patients Taking Nabilone, Between V 1 and V 3 | Safety and tolerability will be evaluated with reference to the following: Adverse Events (AE) | 6 months | 
| Number of Subjects (%) Who Discontinue the Study Due to an AE Between V 1 and V 3 | Safety and tolerability will be evaluated with reference to the following: Number of subjects (%) who discontinue the study due to an AE The reasons for discontinuation will be grouped in discontinuation due to an AE and discontinuation due to other reasons. Both results will be provided separately. | 6 months | 
| Number of Subjects (%) Who Discontinue the Study Due to Other Reasons Than an AE Between V 1 and V 3 | Safety and tolerability will be evaluated with reference to the following: Number of subjects (%) who discontinue the study due to other reasons than an AE The reasons for discontinuation will be grouped in discontinuation due to an AE and discontinuation due to other reasons. Both results will be provided separately. | 6 months | 
| Suicidality in PD Patients Taking Nabilone Between V 1 and V 3 Using the Columbia-Suicide Severity Rating Scale | Change in aggregated data of the Columbia-Suicide Severity Rating Scale (C-SSRS). Different questions for suicidality with the possible answers yes or no. Yes represents a worse outcome. Count of participants with new suicidality is given. | between V 1 and V 3 (6 months) | 
| Hallucinations in PD Patients Taking Nabilone Between V 1 and V 3 | Changes in points of the: Hallucination item (1.2) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome. Participant count with a change in the hallucination item is reported. | between V 1 and V 3 (6 months) | 
| Day-time Sleepiness in PD Patients Taking Nabilone Between V 1 and V 3 | Changes in points of the: Day-time sleepiness item (1.8) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome. | between V 1 and V 3 (6 months) | 
| Orthostatic Hypotension in PD Patients Taking Nabilone Between V 1 and V 3 | Changes in points of the: Orthostatic hypotension item (1.12) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome. | between V 1 and V 3 (6 months) | 
| Subject Compliance in PD Patients Taking Nabilone. | subject incompliance as per drug accountability (%) | between V 1 and V 3 (6 months) | 
| Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone Between V 1 and V 3 | changes in supine and standing blood pressure measurements (mmHg) Row titles: Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at V 1 Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at V 3 Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at V 1 Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at V 3 | between V 1 and V 3 (6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Motor and Non-motor Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3 | Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires: Total and different parts of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Part I: minimum points: 0, maximum points: 52, higher score values indicate a worse outcome. Part II: minimum points: 0, maximum points: 52, higher score values indicate a worse outcome. Part III: minimum points: 0, maximum points: 132, higher score values indicate a worse outcome. Part IV: minimum points: 0, maximum points: 24, higher score values indicate a worse outcome. Total Score: minimum points: 0, maximum points: 272, higher score values indicate a worse outcome. | between V 1 and V 3 (6 months) | 
| Changes in Non-motor Symptoms (NMSS) in Patients With PD Taking Nabilone Between V 1 and V 3 | Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires: Non Motor Symptoms Scale (NMSS) Minimum: 0, maximum: 360, higher score values indicate a worse outcome. | between V 1 and V 3 (6 months) | 
| Changes in Non-motor Symptoms (HADS) in Patients With PD Taking Nabilone Between V 1 and V 3 | Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires: Hospital anxiety and depression scale (HADS), HADS-A assesses anxiety, HADS-D depression. Total scale: minimum: 0, maximum: 42, separate HADS-A/-D score: minimum: 0, maximum: 21. Higher score values indicate a worse outcome. | between V 1 and V 3 (6 months) | 
| Changes in Quality of Life in Patients With PD Taking Nabilone Between V 1 and V 3 | Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires: Parkinson´s Disease Questionnaire - 8 (PDQ-8). Minimum: 0, maximum: 42, higher score values indicate a worse outcome. PDQ-8 was standardized, therefore the score ranges from 0 to 100 (= PDQ-8 Summary Index). | between V 1 and V 3 (6 months) | 
| Changes in Sleepiness in Patients With PD Taking Nabilone Between V 1 and V 3 | Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires: Epworth Sleepiness Scale (ESS) Minimum: 0, maximum: 24, higher score values indicate a worse outcome. | between V 1 and V 3 (6 months) | 
| Changes in Fatigue in Patients With PD Taking Nabilone Between V 1 and V 3 | Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires: Fatigue Severity Scale (FSS). Minimum: 9, maximum: 63, higher score values indicate a worse outcome. | between V 1 and V 3 (6 months) | 
| Changes in Pain in Patients With PD Taking Nabilone Between V 1 and V 3 | Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires: King's Parkinson's disease pain scale (KPPS) Minimum: 0, maximum: 168, higher score values indicate a worse outcome. | between V 1 and V 3 (6 months) | 
| Changes in Impulsive-compulsive Behaviour in Patients With PD Taking Nabilone Between V 1 and V 3 | Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires: Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) Minimum: 0, maximum: 112, higher score values indicate a worse outcome. | between V 1 and V 3 (6 months) | 
| Changes in Overall Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3 | Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires: Clinical Global Impression - Global Improvement (CGI-I) Minimum: 1, maximum: 7, higher score values indicate a worse outcome. | between V 1 and V 3 (6 months) | 
| Changes in Cognitive Function (MoCA) in Patients With PD Taking Nabilone Between V 1 and V 3 | The change of Montreal Cognitive Assessment (MoCA, minimum 0 points, maximum 30 points, higher score values indicate better outcome) 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. | from Screening of the preceding study (NCT03769896) to V 3 of this study (a maximum of 2 years, at study completion) | 
| Changes in Cognitive Function (MMSE) in Patients With PD Taking Nabilone | The change of Mini Mental State Exam (MMSE, minimum 0 points, maximum 30 points, higher score values indicate better outcome) 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. | from screening of the preceding study (NCT03769896) to V 3 of this study (a maximum of 2 years, at study completion) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson´s Disease, cannabinoids, non-motor symptoms