Clinical Trial Results:
Nabilone for non-motor symptoms in Parkinson´s disease: A Randomized Placebo-controlled, double-blind, parallel-group, enriched enrollment randomized withdrawal Study
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Summary
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EudraCT number |
2017-000192-86 |
Trial protocol |
AT |
Global end of trial date |
15 Jul 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Jul 2020
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First version publication date |
29 Jul 2020
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Other versions |
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Summary report(s) |
SmPC Nabilone Clinical Study Protocol 1.4 Complete list of AEs Data Safety Monitoring Board Meeting IMPD_Nabilone IMPD_Placebo Individual Patient Demographics List of patient identifiers Protocol Deviation Log Final report |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NMSNabStudy
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Medical University of Innsbruck
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Sponsor organisation address |
Anichstraße 35, Innsbruck, Austria, 6020
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Public contact |
Clinical Trial Center Neurology, Medizinische Universität Innsbruck, Universitätsklinik für Neurologie, +43 51250425810, raphaela.stolz@tirol-kliniken.at
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Scientific contact |
Clinical Trial Center Neurology, Medizinische Universität Innsbruck, Universitätsklinik für Neurologie, +43 51250425810, raphaela.stolz@tirol-kliniken.at
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Jul 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Jul 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Jul 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary efficacy objective of this study is to demonstrate the efficacy of nabilone concerning non-motor symptoms of patients with Parkinson´s disease, based on the change from baseline to Week 4/Termination visit in the MDS-UPDRS Part I.
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Protection of trial subjects |
For all work involving data collection or management of subjects, the study centre adhered to the law as laid down in the European Regulation (EU) 2016/679 as well as to the national data protection law.
Safety Assessments
Tolerability was described through the: Number of subjects (%) who discontinue the study and the number of subjects (%) who discontinue the study due to AE
Safety Measures included the following: AEs, SAEs, SUSARs, Clinical and laboratory assessment, Vital signs including performance of active orthostatism (measurement of heart rate and blood pressure after 10 minutes of quiet rest in the supine position and at 1, 2, 3, 5, and 10 minutes of active standing), ECG results, Patient´s Compliance, Prior and Concomitant Medication Use, Hallucination item (1.2), OH item (1.12), and Day-time sleepiness item (1.8) of the MDS-UPDRS, C-SSRS
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Oct 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 47
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Worldwide total number of subjects |
47
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EEA total number of subjects |
47
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
18
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From 65 to 84 years |
29
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85 years and over |
0
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Recruitment
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Recruitment details |
Patient recruitment was started in October 2017 and ended in July 2019. The first patient was included in December 2017. | ||||||||||||||
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Pre-assignment
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Screening details |
Forty-eight participants were screened. There was one screening failure due to the use of prohibited concomitant medication. During open-label titration (phase 1) nine patients were either non-responder as defined per protocol (n=5, 10.42%) or discontinued ( 1 drop-out, 3 due to AEs). Thirty-eight patients entered phase 2 and were randomised 1:1. | ||||||||||||||
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Period 1
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Period 1 title |
Phase 1 of the trial = open-label
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Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Nabilone | ||||||||||||||
Arm description |
Phase 1 of the trial was open-label (OL) and nabilone, manufactured by AOP Orphan Pharmaceuticals AG (Vienna, Austria), was given orally daily starting with a dose of 0.25 milligrams (mg, one capsule) in the evening after the baseline visit. It was titrated in 0.25 mg-increments every one to four days after consultation with the study team during regular telephone calls. Dose adjustments were performed until patients met the responder criterion defined as a patient-based rating of their NMS as “much improved” (CGI-I Rating Scale: 2) or “very much improved” (CGI-I Rating Scale: 1) on the 7-point CGI-I Scale. Patients failing to meet this response criterion at the maximum daily dose of 2 mg or patients with intolerable side effects believed to be related to the study drug were discontinued. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Nabilone
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Investigational medicinal product code |
verum
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Other name |
Canemes
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
nabilone, manufactured by AOP Orphan Pharmaceuticals AG (Vienna, Austria), was given orally daily. dose specified during phase 1 of the trial
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Period 2
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Period 2 title |
Phase 2 of the trial - double-blind
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Is this the baseline period? |
Yes [1] | ||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||
Blinding implementation details |
Treatment responders were randomly assigned (1:1) to either nabilone in their individual optimal dose or placebo (corn starch) of matching colour and shape and supplied in identical packaging. Randomisation was performed with a computer-generated randomisation schedule provided by the Department of Medical Statistics of the MUI. Respective medication boxes with either verum or placebo were labelled consecutively (1-48) according to the randomisation list to ensure concealment.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Nabilone | ||||||||||||||
Arm description |
Treatment Arm | ||||||||||||||
Arm type |
Active comparator | ||||||||||||||
Investigational medicinal product name |
Nabilone
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Investigational medicinal product code |
verum
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Other name |
Canemes
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
nabilone, manufactured by AOP Orphan Pharmaceuticals AG (Vienna, Austria), was given orally daily. dose specified during phase 1 of the trial
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Arm title
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Placebo | ||||||||||||||
Arm description |
matching placebo | ||||||||||||||
Arm type |
Placebo | ||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
placebo
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
matching placebo, taken orally daily
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| Notes [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period. Justification: Primary Endpoint is based on period 2 of the trial, therefore baseline values refer to the randomisation visit. |
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| Notes [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Primary Endpoint is based on period 2 of the trial, therefore baseline values refer to the randomisation visit. |
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Baseline characteristics reporting groups
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Reporting group title |
Nabilone
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Reporting group description |
Treatment Arm | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
matching placebo | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Nabilone
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Reporting group description |
Phase 1 of the trial was open-label (OL) and nabilone, manufactured by AOP Orphan Pharmaceuticals AG (Vienna, Austria), was given orally daily starting with a dose of 0.25 milligrams (mg, one capsule) in the evening after the baseline visit. It was titrated in 0.25 mg-increments every one to four days after consultation with the study team during regular telephone calls. Dose adjustments were performed until patients met the responder criterion defined as a patient-based rating of their NMS as “much improved” (CGI-I Rating Scale: 2) or “very much improved” (CGI-I Rating Scale: 1) on the 7-point CGI-I Scale. Patients failing to meet this response criterion at the maximum daily dose of 2 mg or patients with intolerable side effects believed to be related to the study drug were discontinued. | ||
Reporting group title |
Nabilone
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Reporting group description |
Treatment Arm | ||
Reporting group title |
Placebo
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Reporting group description |
matching placebo | ||
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End point title |
change of the MDS-UPDRDS Part 1 | ||||||||||||
End point description |
The primary endpoint of the study was the change from randomisation to week four visit in the Movement Disorders Society – Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Part I (non-motor Experiences of daily living) score.
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End point type |
Primary
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End point timeframe |
The mean durations of phase 2 (i.e. double-blind, withdrawal phase) was 28.37 days ±3.23 (median 28.00 days).
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Statistical analysis title |
Primary endpoint analysis | ||||||||||||
Statistical analysis description |
The primary, secondary, and exploratory endpoints of this study were analysed separately for the nabilone and the placebo group using a Wilcoxon matched-pairs test for within-group comparison (with correction for multiple comparisons with a factor of two) and a Mann–Whitney U test for between-group comparisons. For all analyses, statistical significance was set at a two-sided 5% level.
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Comparison groups |
Placebo v Nabilone
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Number of subjects included in analysis |
38
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Safety and tolerability summaries were based on the safety set which includes all patients receiving at least one dose of study medication during both trial phases. Reporting for Phase 2 (28.37 days ±3.23).
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Adverse event reporting additional description |
Tolerability: n of subjects (%) who discontinue the study and n of subjects (%) who discontinue the study due to AEs
Safety Measures: AEs, SAEs, SUSARs, Clinical and laboratory assessment, Vital signs +performance of active orthostatism, ECG results, Patient´s Compliance, Prior and Concomitant Medication Use, C-SSRS, items of the MDS-UPDRS
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.1
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Reporting groups
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Reporting group title |
Nabilone
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Reporting group description |
Treatment Arm | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
matching placebo | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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26 Jan 2018 |
26th January, 2018: Amendment 1:
Primary reason for the amendment: Eye-tracking was added as an exploratory endpoint. A change in the list of prohibited medication was made.
Protocol Version 1.3
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13 Jul 2018 |
13th July, 2018: Amendment 2: Primary reason for the amendment: The protocol was adapted to reflect changes in EU data protection regulations.
Protocol Version 1.4
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
