Parkinson Disease
Conditions
Keywords
Parkinson´s Disease, cannabinoids, non-motor symptoms
Brief summary
This is a randomized placebo-controlled, double-blind, parallel-group, enriched enrollment randomized withdrawal study assessing the efficacy and safety of nabilone for non-motor symptoms in patients with Parkinson´s Disease. 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. Part 1 is an open-label dose adjustment phase of the study. In eligible patients, a screening period is followed by an open-label nabilone dose optimization phase and a stable phase for at least 1 week. Treatment responders will be included in Part 2 of the study (randomized placebo-controlled, double-blind, parallel-grouped). Part 2 is the placebo-controlled, double-blind, parallel-group randomized withdrawal phase of the study.
Detailed description
This is a randomized placebo-controlled, double-blind, parallel-group, enriched enrollment randomized withdrawal study assessing the efficacy and safety of nabilone for non-motor symptoms in patients with Parkinson´s Disease. 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. Part 1 is the open-label dose adjustment phase of the study. In Part 1, eligible subjects, who have signed the informed consent form at the screening visit, will receive open-label nabilone starting with a dosage of 0.25 mg in the evening. During dose titration and optimization, nabilone will be titrated in 0.25 mg increments (increase by 0.25 mg/ every one to four days) up to a maximum dose of 1 mg twice daily. Patients should be on a stable nabilone dose for at least 1 week afterwards until Baseline Visit (V 0). Part 2 is the placebo-controlled, double-blind, parallel-group randomized withdrawal phase of the study. At Baseline Visit, treatment responders will be included in Part 2 of the study (randomized placebo-controlled, double-blind, parallel-grouped). Responders are randomized in a 1:1 ratio at Baseline Visit to receive either nabilone or matching placebo for 4 weeks + 2 days. The placebo-controlled, double-blind, randomized withdrawal phase will end with a clinic visit (Termination Visit V 1). Following this, the study medication will be tapered in all patients. During this period the patients will receive phone calls every other day. A Safety Telephone Call and a Safety Follow-Up Visit will be performed.
Interventions
DRUGNabilone 0.25 mg
capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
DRUGPlacebo
capsule, corn starch, daily basis
Sponsors
Medical University Innsbruck
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
placebo-controlled, double-blind, parallel-group with 1 : 1 randomization
Intervention model description
randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study
Eligibility
Sex/Gender
ALL
Age
30 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
In order to be eligible for the study subjects must meet all inclusion criteria: 1. Age ≥30 years 2. Diagnosis of Parkinson´s Disease (PD): PD should be either 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. Patient is informed and had enough time and opportunity to think about his/her participation in the study and has signed a current Institutional Review Board-approved informed consent form 7. Contraception 1. Women of childbearing potential must use or attest an acceptable method\* of contraception starting 4 weeks prior to study drug administration and for a minimum of 1 month after study completion. 2. Men with a potentially fertile partner must be willing to use an acceptable method of contraception for the duration of the study and for 3 months after study drug discontinuation or have had a vasectomy.
Exclusion criteria
Patients with any of the following characteristics will be excluded from entering the study: 1. Patient previously participated in any study with nabilone. 2. Current use of cannabinoids or use of cannabinoids within 30 days prior to screening. 3. Patient is currently participating in or has participated in another study of investigational products within 30 days prior to screening. 4. Patient has any form of secondary or atypical parkinsonism (e.g., drug-induced, post stroke). 5. Patient presents with motor complications which are, 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 \> 3 7. Evidence of disturbing (i.e. requiring treatment) impulse control disorder in the participant. Can be resolved through a structural interview during screening period. 8. History of neurosurgical intervention for PD 9. presence of symptomatic orthostatic hypotension at screening (MDS-UPDRS 1.12 \> 2) 10. Use of prohibited medication (e.g. benzodiazepines (except for clonazepam up to a maximum of 1.5 mg per d), lithium, opioids, buspirone, muscle relaxing agents, central nervous system depressing substances, ...) 11. Patients with laboratory values that are out-of-range at Screening (or within 4 weeks prior to Screening) and haven´t been reviewed and documented as not clinically significant by the investigator. Lab Tests can be repeated for confirmation. 12. Patients with known or newly 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. Patients who had a recent suicidal attempt (active, interrupted, aborted) within the past five years or report suicidal ideation within the past 6 months. 15. presence of dementia (MDS-UPDRS 1.1 \> 2, Mini-Mental State Examination of \<24 at the Screening visit) 16. clinically significant or unstable medical or surgical condition at Screening or Baseline visit that may preclude safety and the completion of the study participation (based on the investigator's judgment). 17. Patients with moderate or severe hepatic or renal impairment. 18. Patient has a 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 20. Pregnant women or women planning to become pregnant during the course of the study and nursing women. 21. Patients who are knowingly hypersensitive to any of the components of the investigational medicinal product 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes of Non-motor Symptoms | from baseline to 4 weeks + 2 days | Changes in 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Motor and Different Non-motor Symptoms of PD | from baseline to 4 weeks + 2 days | Changes in Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) 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. |
| Changes in Different Domains of Non-motor Symptoms of PD | from baseline to 4 weeks + 2 days | mood/anxiety domain of MDS-UPDRS Part I (items 1.3 and 1.4) and different other domains of NMSS and MDS-UPDRS part I Each items scores 0 to 4 points with higher score values indicating a worse outcome. |
| Changes in Non-motor Symptoms of PD | from baseline to 4 weeks + 2 days | Non Motor Symptoms Scale (NMSS) Minimum: 0, maximum: 360, higher score values indicate a worse outcome. |
| Clinical Global Impression - Global Improvement (CGI-I) Scale | Values of the Termination visit (4 weeks + 2 days from baseline) | Clinical Global Impression - Global Improvement (CGI-I) scale Minimum: 1, maximum: 7, higher score values indicate a worse outcome. |
| Incidence of AEs and Number of Withdrawals in PD Patients Taking Nabilone. | from baseline to 4 weeks + 2 days | 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): total number of patients with all adverse events is reported (no reporting threshold) |
| Suicidality in PD Patients Taking Nabilone. | from baseline to 4 weeks + 2 days | Assessment of aggregated data (suicidality present / no suicidality) of the Columbia-Suicide Severity Rating Scale (C-SSRS). The scale consists of questions for suicidality that can be answered with either yes or no. The answer no indicates no wish to be dead, no suicidal ideations, or suicidal attempts. No minimum or maximum score values can be provided. The values provided represent the number of patients with (new) suicidality. |
| Change in Hallucinations in PD Patients Taking Nabilone | from baseline to 4 weeks + 2 days | Number of patients with changes in the points of the Hallucination item (1.2) of the Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS). |
| Day-time Sleepiness in PD Patients Taking Nabilone: MDS-UPDRS | from baseline to week 4 + 2 days | Changes in points of the Day-time sleepiness item (1.8) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) , minimum of 0, maximum of 4 points, higher score values representing a worse outcome |
| Subject Incompliance in PD Patients Taking Nabilone | from baseline to week 4 + 2 days | subject incompliance as per drug accountability. |
| Weight (kg) in PD Patients Taking Nabilone. | from baseline to week 4 + 2 days | changes in weight (kg) |
| Changes in Temperature (Degree Celsius) in PD Patients Taking Nabilone. | from baseline to week 4 + 2 days | changes in temperature (degree Celsius) |
| Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone. | values from baseline and week 4 + 2 days | changes in supine and standing blood pressure measurements (mmHg) Row titles: 1. Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at the baseline visit 2. Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at the week 4 - visit 3. Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at the baseline visit 4. Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at the week 4 - visit |
| Changes in Quality of Life of PD | from baseline to week 4 + 2 days | Parkinson´s Disease Questionnaire - 39 (PDQ-39) Minimum: 0, maximum: 156, higher score values indicate a worse outcome. Values were standardized = PDQ-39 Summary Index (SI, the score of each subdomain was divided by the number of questions of that domain and then multiplied by hundred, the sum score is the sum of the results of all 8 domains) |
| Orthostatic Hypotension in PD Patients Taking Nabilone | from baseline to week 4 + 2 days | Changes in points of the Orthostatic hypotension (OH) item (1.12) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS), minimum of 0, maximum of 4 points, higher score values representing a worse outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Exploratory Objective of This Study Will be an Eye-tracking Evaluation in PD Patients Taking Nabilone or Placebo. | Maximum of 104 days | Change of the reaction time (seconds) between the Screening visit (Part 1) and the Termination visit (Part 2) as measured by the Eye-tracking examination. |
Countries
Austria
Participant flow
Recruitment details
location: Medical Clinic, period: October 2017 to July 2019
Pre-assignment details
Phase 1: open-label nabilone titration (0.25mg - 2mg). Phase 2: double-blind phase There was one screening failure due to the use of prohibited concomitant medication.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group Nabilone 0.25 mg
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis | 19 |
| Placebo Group Placebo (corn starch)
Placebo: capsule, corn starch, daily basis | 19 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Open-label Phase | Adverse Event | 3 | 0 |
| Open-label Phase | Lack of Efficacy | 5 | 0 |
| Open-label Phase | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo Group | Total | Treatment Group |
|---|---|---|---|
| Age, Continuous | 63.95 years STANDARD_DEVIATION 8.04 | 65.05 years STANDARD_DEVIATION 8.12 | 65.38 years STANDARD_DEVIATION 7.94 |
| Disease duration | 7.39 years STANDARD_DEVIATION 5.14 | 7.61 years STANDARD_DEVIATION 5.24 | 7.83 years STANDARD_DEVIATION 5.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 38 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hoehn and Yahr Scale | 1.95 units on a scale STANDARD_DEVIATION 0.41 | 1.89 units on a scale STANDARD_DEVIATION 0.45 | 1.84 units on a scale STANDARD_DEVIATION 0.5 |
| MDS-UPDRS-I | 12.26 units on a scale STANDARD_DEVIATION 5.85 | 12.89 units on a scale STANDARD_DEVIATION 5.14 | 13.53 units on a scale STANDARD_DEVIATION 4.39 |
| MDS-UPDRS Total Score | 52.05 units on a scale STANDARD_DEVIATION 14.75 | 52.05 units on a scale STANDARD_DEVIATION 19.04 | 52.05 units on a scale STANDARD_DEVIATION 22.97 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 00 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 38 Participants | 19 Participants |
| Region of Enrollment Austria | 19 participants | 38 participants | 19 participants |
| Sex: Female, Male Female | 5 Participants | 14 Participants | 9 Participants |
| Sex: Female, Male Male | 14 Participants | 24 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 30 / 47 | 4 / 19 | 9 / 19 |
| serious Total, serious adverse events | 0 / 47 | 0 / 19 | 0 / 19 |
Outcome results
Primary
Changes of Non-motor Symptoms
Changes in 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.
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group | Changes of Non-motor Symptoms | 1.00 units on a scale |
| Placebo Group | Changes of Non-motor Symptoms | 2.63 units on a scale |
Secondary
Change in Hallucinations in PD Patients Taking Nabilone
Number of patients with changes in the points of the Hallucination item (1.2) of the Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS).
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Change in Hallucinations in PD Patients Taking Nabilone | 0 Participants |
| Placebo Group | Change in Hallucinations in PD Patients Taking Nabilone | 0 Participants |
Secondary
Changes in Different Domains of Non-motor Symptoms of PD
mood/anxiety domain of MDS-UPDRS Part I (items 1.3 and 1.4) and different other domains of NMSS and MDS-UPDRS part I Each items scores 0 to 4 points with higher score values indicating a worse outcome.
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Group | Changes in Different Domains of Non-motor Symptoms of PD | MDS-UPDRS 1.3 Depressed Mood | 0.11 units on a scale |
| Treatment Group | Changes in Different Domains of Non-motor Symptoms of PD | MDS-UPDRS 1.4 Anxious Mood | -0.16 units on a scale |
| Treatment Group | Changes in Different Domains of Non-motor Symptoms of PD | MDS-UPDRS 1.7 Nighttime sleep problems | 0.05 units on a scale |
| Placebo Group | Changes in Different Domains of Non-motor Symptoms of PD | MDS-UPDRS 1.3 Depressed Mood | 0.16 units on a scale |
| Placebo Group | Changes in Different Domains of Non-motor Symptoms of PD | MDS-UPDRS 1.4 Anxious Mood | 0.21 units on a scale |
| Placebo Group | Changes in Different Domains of Non-motor Symptoms of PD | MDS-UPDRS 1.7 Nighttime sleep problems | 1.79 units on a scale |
Secondary
Changes in Motor and Different Non-motor Symptoms of PD
Changes in Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) 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.
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Group | Changes in Motor and Different Non-motor Symptoms of PD | MDS-UPDRS II | 0.47 units on a scale |
| Treatment Group | Changes in Motor and Different Non-motor Symptoms of PD | MDS-UPDRS III | 0.53 units on a scale |
| Placebo Group | Changes in Motor and Different Non-motor Symptoms of PD | MDS-UPDRS II | 0.90 units on a scale |
| Placebo Group | Changes in Motor and Different Non-motor Symptoms of PD | MDS-UPDRS III | 2.63 units on a scale |
Secondary
Changes in Non-motor Symptoms of PD
Fatigue Severity Scale (FSS) Minimum: 9, maximum: 63, higher score values indicate a worse outcome.
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group | Changes in Non-motor Symptoms of PD | -4.00 units on a scale |
| Placebo Group | Changes in Non-motor Symptoms of PD | 0.00 units on a scale |
Secondary
Changes in Non-motor Symptoms of PD
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) Minimum: 0, maximum: 112, higher score values indicate a worse outcome.
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group | Changes in Non-motor Symptoms of PD | -0.68 units on a scale |
| Placebo Group | Changes in Non-motor Symptoms of PD | 0.05 units on a scale |
Secondary
Changes in Non-motor Symptoms of PD
Montreal Cognitive Assessment (MoCA) Minimum: 0, maximum: 30, higher score values indicate better outcome.
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group | Changes in Non-motor Symptoms of PD | 0.74 units on a scale |
| Placebo Group | Changes in Non-motor Symptoms of PD | 0.00 units on a scale |
Secondary
Changes in Non-motor Symptoms of PD
Visual Analog Scale (VAS) of Pain Minimum: 0 mm, maximum: 10 mm, higher score values indicate a worse outcome.
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group | Changes in Non-motor Symptoms of PD | 6.58 millimeters on a scale |
| Placebo Group | Changes in Non-motor Symptoms of PD | 2.16 millimeters on a scale |
Secondary
Changes in Non-motor Symptoms of PD
King's Parkinson's disease pain scale (KPPS) Minimum: 0, maximum: 168, higher score values indicate a worse outcome.
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group | Changes in Non-motor Symptoms of PD | 1.58 units on a scale |
| Placebo Group | Changes in Non-motor Symptoms of PD | 2.84 units on a scale |
Secondary
Changes in Non-motor Symptoms of PD
Non Motor Symptoms Scale (NMSS) Minimum: 0, maximum: 360, higher score values indicate a worse outcome.
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group | Changes in Non-motor Symptoms of PD | 4.05 score on a scale |
| Placebo Group | Changes in Non-motor Symptoms of PD | 11.00 score on a scale |
Secondary
Changes in Non-motor Symptoms of PD
Hospital anxiety and depression scale (HAD-S) Minimum: 0, maximum: 42, higher score values indicate a worse outcome.
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Group | Changes in Non-motor Symptoms of PD | Hospital anxiety and depression scale - Anxiety | 0.26 units on a scale |
| Treatment Group | Changes in Non-motor Symptoms of PD | Hospital anxiety and depression scale - Depression | 0.32 units on a scale |
| Placebo Group | Changes in Non-motor Symptoms of PD | Hospital anxiety and depression scale - Anxiety | 0.05 units on a scale |
| Placebo Group | Changes in Non-motor Symptoms of PD | Hospital anxiety and depression scale - Depression | 0.16 units on a scale |
Secondary
Changes in Non-motor Symptoms of PD
Epworth Sleepiness Scale (ESS) Minimum: 0, maximum: 24, higher score values indicate a worse outcome.
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group | Changes in Non-motor Symptoms of PD | -0.74 units on a scale |
| Placebo Group | Changes in Non-motor Symptoms of PD | -0.79 units on a scale |
Secondary
Changes in Quality of Life of PD
Parkinson´s Disease Questionnaire - 39 (PDQ-39) Minimum: 0, maximum: 156, higher score values indicate a worse outcome. Values were standardized = PDQ-39 Summary Index (SI, the score of each subdomain was divided by the number of questions of that domain and then multiplied by hundred, the sum score is the sum of the results of all 8 domains)
Time frame: from baseline to week 4 + 2 days
Population: PDQ-39 SI values reported
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group | Changes in Quality of Life of PD | -0.49 units on a scale |
| Placebo Group | Changes in Quality of Life of PD | -0.47 units on a scale |
Secondary
Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone.
changes in supine and standing blood pressure measurements (mmHg) Row titles: 1. Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at the baseline visit 2. Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at the week 4 - visit 3. Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at the baseline visit 4. Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at the week 4 - visit
Time frame: values from baseline and week 4 + 2 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group | Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone. | Baseline: Change supine - 3 min standing, SBP | 1.47 mmHg | Standard Deviation 13.88 |
| Treatment Group | Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone. | week4: Change supine - 3 min standing, SBP | -1.84 mmHg | Standard Deviation 10.68 |
| Treatment Group | Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone. | Baseline: Change supine - 3 min standing, DBP | 3.79 mmHg | Standard Deviation 5.84 |
| Treatment Group | Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone. | week4: Change supine - 3 min standing, DBP | 4.11 mmHg | Standard Deviation 5.95 |
| Placebo Group | Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone. | week4: Change supine - 3 min standing, DBP | -0.79 mmHg | Standard Deviation 7.9 |
| Placebo Group | Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone. | Baseline: Change supine - 3 min standing, SBP | -4.05 mmHg | Standard Deviation 11.53 |
| Placebo Group | Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone. | Baseline: Change supine - 3 min standing, DBP | 3.16 mmHg | Standard Deviation 6.07 |
| Placebo Group | Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone. | week4: Change supine - 3 min standing, SBP | -2.95 mmHg | Standard Deviation 17.96 |
Secondary
Changes in Temperature (Degree Celsius) in PD Patients Taking Nabilone.
changes in temperature (degree Celsius)
Time frame: from baseline to week 4 + 2 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Changes in Temperature (Degree Celsius) in PD Patients Taking Nabilone. | 0.17 degree Celsius | Standard Deviation 0.56 |
| Placebo Group | Changes in Temperature (Degree Celsius) in PD Patients Taking Nabilone. | 0.35 degree Celsius | Standard Deviation 0.48 |
Secondary
Clinical Global Impression - Global Improvement (CGI-I) Scale
Clinical Global Impression - Global Improvement (CGI-I) scale Minimum: 1, maximum: 7, higher score values indicate a worse outcome.
Time frame: Values of the Termination visit (4 weeks + 2 days from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Clinical Global Impression - Global Improvement (CGI-I) Scale | 4.95 units on a scale | Standard Deviation 0.71 |
| Placebo Group | Clinical Global Impression - Global Improvement (CGI-I) Scale | 4.42 units on a scale | Standard Deviation 0.61 |
Secondary
Day-time Sleepiness in PD Patients Taking Nabilone: MDS-UPDRS
Changes in points of the Day-time sleepiness item (1.8) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) , minimum of 0, maximum of 4 points, higher score values representing a worse outcome
Time frame: from baseline to week 4 + 2 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group | Day-time Sleepiness in PD Patients Taking Nabilone: MDS-UPDRS | 0.26 units on a scale |
| Placebo Group | Day-time Sleepiness in PD Patients Taking Nabilone: MDS-UPDRS | 0.11 units on a scale |
Secondary
Incidence of AEs and Number of Withdrawals in PD Patients Taking Nabilone.
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): total number of patients with all adverse events is reported (no reporting threshold)
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Group | Incidence of AEs and Number of Withdrawals in PD Patients Taking Nabilone. | Number of subjects who discontinue the study | 0 Participants |
| Treatment Group | Incidence of AEs and Number of Withdrawals in PD Patients Taking Nabilone. | Number of subjects who discontinue due to AEs | 0 Participants |
| Treatment Group | Incidence of AEs and Number of Withdrawals in PD Patients Taking Nabilone. | Total number of patients with Adverse Events | 6 Participants |
| Placebo Group | Incidence of AEs and Number of Withdrawals in PD Patients Taking Nabilone. | Number of subjects who discontinue the study | 0 Participants |
| Placebo Group | Incidence of AEs and Number of Withdrawals in PD Patients Taking Nabilone. | Number of subjects who discontinue due to AEs | 0 Participants |
| Placebo Group | Incidence of AEs and Number of Withdrawals in PD Patients Taking Nabilone. | Total number of patients with Adverse Events | 8 Participants |
Secondary
Orthostatic Hypotension in PD Patients Taking Nabilone
Changes in points of the Orthostatic hypotension (OH) item (1.12) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS), minimum of 0, maximum of 4 points, higher score values representing a worse outcome.
Time frame: from baseline to week 4 + 2 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group | Orthostatic Hypotension in PD Patients Taking Nabilone | 0.21 units on a scale |
| Placebo Group | Orthostatic Hypotension in PD Patients Taking Nabilone | -0.26 units on a scale |
Secondary
Subject Incompliance in PD Patients Taking Nabilone
subject incompliance as per drug accountability.
Time frame: from baseline to week 4 + 2 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Subject Incompliance in PD Patients Taking Nabilone | 0 Participants |
| Placebo Group | Subject Incompliance in PD Patients Taking Nabilone | 0 Participants |
Secondary
Suicidality in PD Patients Taking Nabilone.
Assessment of aggregated data (suicidality present / no suicidality) of the Columbia-Suicide Severity Rating Scale (C-SSRS). The scale consists of questions for suicidality that can be answered with either yes or no. The answer no indicates no wish to be dead, no suicidal ideations, or suicidal attempts. No minimum or maximum score values can be provided. The values provided represent the number of patients with (new) suicidality.
Time frame: from baseline to 4 weeks + 2 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Suicidality in PD Patients Taking Nabilone. | 0 Participants |
| Placebo Group | Suicidality in PD Patients Taking Nabilone. | 0 Participants |
Secondary
Weight (kg) in PD Patients Taking Nabilone.
changes in weight (kg)
Time frame: from baseline to week 4 + 2 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Weight (kg) in PD Patients Taking Nabilone. | -0.70 kg | Standard Deviation 2.33 |
| Placebo Group | Weight (kg) in PD Patients Taking Nabilone. | -0.52 kg | Standard Deviation 2.37 |
Other Pre-specified
The Exploratory Objective of This Study Will be an Eye-tracking Evaluation in PD Patients Taking Nabilone or Placebo.
Change of the reaction time (seconds) between the Screening visit (Part 1) and the Termination visit (Part 2) as measured by the Eye-tracking examination.
Time frame: Maximum of 104 days
Other Pre-specified
The Exploratory Objective of This Study Will be an Eye-tracking Evaluation in PD Patients Taking Nabilone or Placebo.
Change of attention span and ability to concentrate (error rate, correct trials) between the Screening visit (Part 1) and the Termination visit (Part 2) as measured by the Eye-tracking examination.
Time frame: Maximum of 104 days