Clinical Trial Results:
Nabilone for non-motor symptoms in Parkinson’s disease: An open-label study to evaluate long-term safety and efficacy
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Summary
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EudraCT number |
2017-004253-16 |
Trial protocol |
AT |
Global end of trial date |
31 Jan 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Feb 2021
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First version publication date |
10 Feb 2021
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Other versions |
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Summary report(s) |
Adverse event Log IMPD Nabilone Data Safety Board Meeting Demographics of Individual Patients SAE Form_002 SAE Form_003 SAE Form_004 SAE Form_006 Clinical study protocol V1.3 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 |
NMSNab2study
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03773796 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Medical University of Innsbruck, Department of Neurology
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Sponsor organisation address |
Anichstraße 35, Innsbruck, Austria, 6020
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Public contact |
Clinical Trial Center Neurology, Medical University of Innsbruck, Department of Neurology, 6801449268 51250425810, klaus.seppi@tirol-kliniken.at
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Scientific contact |
Clinical Trial Center Neurology, Medical University of Innsbruck, Department of Neurology, 6801449268 51250425810, klaus.seppi@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 |
23 Jan 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jan 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jan 2020
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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 objective of this study is to evaluate long-term safety and tolerability of nabilone in PD patients.
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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. Permission for the conduct of the trial was received from the ethics committee (IEC) of the Medical University of Innsbruck (MUI) on February 07th, 2018 (reference number: 1214/2017) and the Austrian regulatory authorities approved the study on the 13th of April 2018. One substantial amendment with changes in prohibited concomitant medication, study team members, and to conform to the EU Data Protection Law 2018 have been approved by the EC of the MUI and non-prohibited by the regulatory authorities. Two amendments for changes in study team members were approved by the EC of the MUI. Informed consent was obtained from all individual participants included in the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (IEC MUI, reference number 1214/2017 and the national regulatory authorities) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. As the trials primary endpoint was safety, (serious) adverse events, reasons for discontinuation of the study, clinical examination, vital signs, compliance, and suicidality were documented and/or closely monitored.
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Background therapy |
All Anti-PD Medications were allowed in this study. The addition of any new anti-PD medication or other prescribed / non-prescribed drugs were allowed during the study as well as changes to frequency or intervals between doses. All non-pharmacological therapies (e.g., physical therapy, exercise, yoga) the patient wanted to perform to improve his/her Parkinson symptoms were allowed to be continued during participation in the study. During the trial, such non-pharmacological therapies were allowed to be started as well. The concomitant non-pharmacological therapies should have been kept on the same level during the study. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Aug 2018
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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: 22
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Worldwide total number of subjects |
22
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EEA total number of subjects |
22
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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) |
8
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From 65 to 84 years |
14
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85 years and over |
0
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Recruitment
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Recruitment details |
Twenty-two patients participated in the NMS-Nab2 study between August 10, 2018, and January 31, 2020 (last patient last visit). There was no screening failure. Up-titration was started in all patients. One patient was a non-responder and therefore discontinued before V 1. Two patients were drop-outs (reasons: AE, own will). | ||||||||||||||
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Pre-assignment
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Screening details |
All 38 patients that finished the double-blind phase of the preceding NMS-Nab study were assessed for eligibility. Reasons for declined partic. in NMS-Nab2: satisfaction with symptomatic control (4), planned surgery (2), wish for modification of PD treatment regime (4), cannabinoid treatment outside of study (2), scheduling difficulties (3), other | ||||||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Blinding implementation details |
no blinding, open-label study
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Arms
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Arm title
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Nabilone | ||||||||||||||
Arm description |
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 screening 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 titration phase of the trial
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full data set
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Safety and tolerability summaries were based on a safety set which included all patients receiving at least one dose of study medication and completing at least V 1. Additionally, summaries of baseline and demographic data were produced out of the safety set. The efficacy analyses for the secondary endpoints included all screened subjects with at least one Visit after screening.
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End points reporting groups
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Reporting group title |
Nabilone
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Reporting group description |
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 screening 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. | ||
Subject analysis set title |
Full data set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Safety and tolerability summaries were based on a safety set which included all patients receiving at least one dose of study medication and completing at least V 1. Additionally, summaries of baseline and demographic data were produced out of the safety set. The efficacy analyses for the secondary endpoints included all screened subjects with at least one Visit after screening.
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End point title |
primary endpoint [1] | ||||||
End point description |
The primary endpoint of the study was safety (see AE page). On parameter assessed in this category was the C-SSRS describing suicidality. No patient experienced suicidality, therefore the count is 0.
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End point type |
Primary
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End point timeframe |
V 1 to V 3, 6 months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary endpoint was safety. Please refer to the Adverse event - section. |
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| No statistical analyses for this end point | |||||||
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End point title |
change of the different MDS-UPDRDS Parts | ||||||||||||||||||||
End point description |
The secondary efficacy criteria were measured as the change in the different clinical scales and questionnaires regarding motor symptoms and different domains of non-motor symptoms in Parkinson´s Disease between V 1 and V 3.
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End point type |
Secondary
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End point timeframe |
V 1 to V 3, 6 months
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
change in other secondary endpoints | ||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
V 1 to V 3, 6 months
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
change in scores for cognition | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
variable, scores at the screening visit of the preceeding NMS-Nab1 study were compared to V 3 of this study
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
V 1 to V 3 = 6 months
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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 |
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 screening 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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06 Sep 2018 |
(Substantial) Amendment 1: Primary reason for the amendment: The protocol was adapted to reflect changes in EU data protection regulations. A change in the list of prohibited medication was made. Changes in study team members were added.
Protocol Version 1.1
Approved by the EC: 25th August 2018
Non-prohibition by the regulatory authorities: 6th September 2018
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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 | |||
