Trial Outcomes & Findings for Nabilone for Non-motor Symptoms in Parkinson's Disease (NCT NCT03773796)

NCT ID: NCT03773796

Last Updated: 2021-03-02

Results Overview

Safety and tolerability will be evaluated with reference to the following: Adverse Events (AE)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 22 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2021-03-02

Participant Flow

Participant milestones

Measure	Treatment Group Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Overall Study STARTED	22
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Treatment Group Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	1
Overall Study Lack of Efficacy	1

Baseline Characteristics

Nabilone for Non-motor Symptoms in Parkinson's Disease

Baseline characteristics by cohort

Measure	Treatment Group n=21 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Age, Continuous	67.23 years STANDARD_DEVIATION 6.15 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Disease duration	9.30 years STANDARD_DEVIATION 6.04 • n=5 Participants
Education	12.81 years STANDARD_DEVIATION 2.53 • n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: primary endpoint was safety, please refer to Adverse events section.

Safety and tolerability will be evaluated with reference to the following:

Adverse Events (AE)

Outcome measures

Measure	Treatment Group n=21 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
AEs in PD Patients Taking Nabilone, Between V 1 and V 3	39 adverse events

PRIMARY outcome

Timeframe: 6 months

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.

Outcome measures

Measure	Treatment Group n=21 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Number of Subjects (%) Who Discontinue the Study Due to an AE Between V 1 and V 3	1 Participants

PRIMARY outcome

Timeframe: 6 months

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.

Outcome measures

Measure	Treatment Group n=21 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Number of Subjects (%) Who Discontinue the Study Due to Other Reasons Than an AE Between V 1 and V 3	1 Participants

PRIMARY outcome

Timeframe: between V 1 and V 3 (6 months)

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.

Outcome measures

Measure	Treatment Group n=21 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Suicidality in PD Patients Taking Nabilone Between V 1 and V 3 Using the Columbia-Suicide Severity Rating Scale	0 Participants

PRIMARY outcome

Timeframe: between V 1 and V 3 (6 months)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Hallucinations in PD Patients Taking Nabilone Between V 1 and V 3 no change	18 Participants
Hallucinations in PD Patients Taking Nabilone Between V 1 and V 3 less hallucinations	1 Participants
Hallucinations in PD Patients Taking Nabilone Between V 1 and V 3 more hallucinations	0 Participants

PRIMARY outcome

Timeframe: between V 1 and V 3 (6 months)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Day-time Sleepiness in PD Patients Taking Nabilone Between V 1 and V 3	-0.05 units on a scale Standard Deviation 0.83

PRIMARY outcome

Timeframe: between V 1 and V 3 (6 months)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Orthostatic Hypotension in PD Patients Taking Nabilone Between V 1 and V 3	-0.16 units on a scale Standard Deviation 0.77

PRIMARY outcome

Timeframe: between V 1 and V 3 (6 months)

subject incompliance as per drug accountability (%)

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Subject Compliance in PD Patients Taking Nabilone.	0 Participants

PRIMARY outcome

Timeframe: between V 1 and V 3 (6 months)

Population: 21 patients for V 1 and 19 for V 3 analyzed.

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 V 1

2. Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at V 3

3. Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at V 1

4. Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at V 3

Outcome measures

Measure	Treatment Group n=21 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone Between V 1 and V 3 1. change of SBP from supine to standing position for 3 min at V 1	5.14 mmHg Standard Deviation 7.15
Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone Between V 1 and V 3 2. change of SBP from supine to standing position for 3 min at V 3	6.05 mmHg Standard Deviation 11.40
Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone Between V 1 and V 3 3. change of DBP from supine to standing position for 3 min at V 1	0.76 mmHg Standard Deviation 6.96
Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone Between V 1 and V 3 4. change of DBP from supine to standing position for 3 min at V 3	-0.42 mmHg Standard Deviation 9.05

SECONDARY outcome

Timeframe: between V 1 and V 3 (6 months)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Changes in Motor and Non-motor Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3 MDS-UPDRS I	1.58 units on a scale Standard Deviation 13.87
Changes in Motor and Non-motor Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3 MDS-UPDRS II	-0.58 units on a scale Standard Deviation 3.49
Changes in Motor and Non-motor Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3 MDS-UPDRS III	-1.89 units on a scale Standard Deviation 6.88
Changes in Motor and Non-motor Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3 MDS-UPDRS IV	-0.16 units on a scale Standard Deviation 2.14
Changes in Motor and Non-motor Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3 MDS-UPDRS Total Score	-1.05 units on a scale Standard Deviation 15.90

SECONDARY outcome

Timeframe: between V 1 and V 3 (6 months)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Changes in Non-motor Symptoms (NMSS) in Patients With PD Taking Nabilone Between V 1 and V 3	-4.84 units on a scale Standard Deviation 18.08

SECONDARY outcome

Timeframe: between V 1 and V 3 (6 months)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Changes in Non-motor Symptoms (HADS) in Patients With PD Taking Nabilone Between V 1 and V 3 HADS-A	-0.16 units on a scale Standard Deviation 1.30
Changes in Non-motor Symptoms (HADS) in Patients With PD Taking Nabilone Between V 1 and V 3 HADS-D	1.00 units on a scale Standard Deviation 2.08

SECONDARY outcome

Timeframe: between V 1 and V 3 (6 months)

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).

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Changes in Quality of Life in Patients With PD Taking Nabilone Between V 1 and V 3	-2.96 units on a scale Standard Deviation 9.11

SECONDARY outcome

Timeframe: between V 1 and V 3 (6 months)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Changes in Sleepiness in Patients With PD Taking Nabilone Between V 1 and V 3	0.11 units on a scale Standard Deviation 2.75

SECONDARY outcome

Timeframe: between V 1 and V 3 (6 months)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Changes in Fatigue in Patients With PD Taking Nabilone Between V 1 and V 3	4.26 units on a scale Standard Deviation 10.08

SECONDARY outcome

Timeframe: between V 1 and V 3 (6 months)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Changes in Pain in Patients With PD Taking Nabilone Between V 1 and V 3	-6.84 units on a scale Standard Deviation 15.12

SECONDARY outcome

Timeframe: between V 1 and V 3 (6 months)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Changes in Impulsive-compulsive Behaviour in Patients With PD Taking Nabilone Between V 1 and V 3	0.11 units on a scale Standard Deviation 1.41

SECONDARY outcome

Timeframe: between V 1 and V 3 (6 months)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Changes in Overall Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3	-1.16 units on a scale Standard Deviation 1.30

SECONDARY outcome

Timeframe: from Screening of the preceding study (NCT03769896) to V 3 of this study (a maximum of 2 years, at study completion)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Changes in Cognitive Function (MoCA) in Patients With PD Taking Nabilone Between V 1 and V 3	-0.11 units on a scale Standard Deviation 1.94

SECONDARY outcome

Timeframe: from screening of the preceding study (NCT03769896) to V 3 of this study (a maximum of 2 years, at study completion)

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.

Outcome measures

Measure	Treatment Group n=19 Participants Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Changes in Cognitive Function (MMSE) in Patients With PD Taking Nabilone	0.42 units on a scale Standard Deviation 1.84

OTHER_PRE_SPECIFIED outcome

Timeframe: a maximum of 2 years, measurement at V2 visit

Change of the reaction time (seconds), between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: a maximum of 2 years, measurement at V2 visit

Change of attention span (error rate, correct trials) between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: a maximum of 2 years, measurement at V2 visit

Change of ability to concentrate (error rate, correct trials) between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.

Outcome measures

Outcome data not reported

Adverse Events

Treatment Group

Serious events: 4 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment Group n=22 participants at risk Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Neoplasms benign, malignant and unspecified (incl cysts and polyps) rectum carcinoma	4.5% 1/22 • Number of events 1 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	4.5% 1/22 • Number of events 1 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Nervous system disorders Worsening of Parkinson´s disease symptoms	4.5% 1/22 • Number of events 1 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Gastrointestinal disorders Vomiting	4.5% 1/22 • Number of events 1 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.

Other adverse events

Measure	Treatment Group n=22 participants at risk Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Infections and infestations respiratory tract infection	13.6% 3/22 • Number of events 4 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Nervous system disorders Concentration difficulties	9.1% 2/22 • Number of events 3 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Nervous system disorders intermittant falls	13.6% 3/22 • Number of events 3 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Renal and urinary disorders Urinary tract infection	4.5% 1/22 • Number of events 2 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Nervous system disorders transient numbness of the face	9.1% 2/22 • Number of events 2 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Metabolism and nutrition disorders Osteopenia	9.1% 2/22 • Number of events 2 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Nervous system disorders Insomnia	9.1% 2/22 • Number of events 2 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Musculoskeletal and connective tissue disorders Back pain	4.5% 1/22 • Number of events 2 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Nervous system disorders Worsening of Parkinson´s Disease symptoms	9.1% 2/22 • Number of events 2 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Musculoskeletal and connective tissue disorders Osteoarthropathy	4.5% 1/22 • Number of events 2 • V1 to V 3, 6 months definitions do not differ Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.

Additional Information

Prof. Klaus Seppi

Medical University of Innsbruck

Phone: 004351250481553

Email: klaus.seppi@tirol-kliniken.at

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place