Clinical Trial Results:
THE ROLE OF BUSPIRONE IN ATTENUATING LEVODOPA-INDUCED DYSKINESIAS IN PATIENTS WITH PARKINSON'S DISEASE: A CLINICAL AND POSITRON EMISSION TOMOGRAPHY STUDY WITH 11C-PHNO.
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Summary
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EudraCT number |
2014-005422-35 |
Trial protocol |
GB |
Global end of trial date |
23 Jan 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Oct 2018
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First version publication date |
12 Oct 2018
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Other versions |
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Summary report(s) |
2014-005422-35_Results_upload |
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 |
14HH2382
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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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Other trial identifiers |
Imperial College Joint Research Compliance Office: 14HH2382, NIHR Portfolio Public database: 139087, Local Clinical Research Network: 139087 | ||
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Sponsors
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Sponsor organisation name |
Imperial College London
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Sponsor organisation address |
St Mary's Campus - JRCO, Praed Street, London, United Kingdom, W2 1NY
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Public contact |
Gary Roper, Imperial College London - Imperial College NHS Trust, +44 (0)2075941872, gary.roper@imperial.ac.uk
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Scientific contact |
Gary Roper, Imperial College London - Imperial College NHS Trust, +44 (0)2075941872, gary.roper@imperial.ac.uk
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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 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Jan 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Jan 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To demonstrate that buspirone which is a serotonine (5HT1A) antagonist will reduce the levels of synaptic dopamine generated from the serotonergic terminals after L−dopa administration. This will be associated with a reduction in dyskinesia intensity in PD patients.
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Protection of trial subjects |
Patients were followed up clinically before, during and after their participation in this clinical study.
The research team is the team directly involved in their medical care.
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Background therapy |
n/a | ||
Evidence for comparator |
n/a | ||
Actual start date of recruitment |
15 Apr 2015
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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 |
United Kingdom: 8
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Worldwide total number of subjects |
8
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EEA total number of subjects |
8
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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) |
3
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
The proposed number of participants was originally 24. However, recruitment was slower than expected. When 8 participants were enrolled in the study, the Sponsor discussed with the research team whether to perform an interim analysis to assess the efficacy of Buspirone in order to apply for extending the recruitment period. | |||||||||
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Pre-assignment
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Screening details |
At screening, all patients had a clinical diagnosis of idiopathic Parkinson's disease. Patients with other neurological conditions, psychiatric disorders, history of depression and or anxiety were excluded. All patients were recruited from Specialist NHS Movement Disorders outpatient clinics by the research team. | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
8 | |||||||||
Number of subjects completed |
8 | |||||||||
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Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Assessor | |||||||||
Blinding implementation details |
The subjects were randomised into two subgroups:
Group a: 12 PD patients with dyskinesias to receive 0.20mg/kg of Buspirone prior to LDOPA
administration. The effects of Buspirone will be compared to placebo.
Group b: 12 PD patients with dyskinesias to receive 0.10mg/kg of Buspirone prior to LDOPA
administration. The effects of Buspirone will be compared to placebo.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Buspirone 0.10mg/kg and Placebo | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Buspirone Hydrochloride
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
0.10mg/kg oral
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Investigational medicinal product name |
Ascorbic acid
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Ascorbic acid 50mg oral
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Arm title
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Buspirone 0.20mg/kg and Placebo | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Buspirone Hydrochloride
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Buspirone 02.mg/kg oral
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Investigational medicinal product name |
Ascorbic acid
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Ascorbic acid 50mg oral
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Baseline characteristics reporting groups
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Reporting group title |
Treatment period
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Buspirone 0.10mg/kg and Placebo
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Reporting group description |
- | ||
Reporting group title |
Buspirone 0.20mg/kg and Placebo
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Reporting group description |
- | ||
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End point title |
The effect of Buspirone in improving dyskinesias' severity | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
To see an effect of Buspirone in improving dyskinesias during the acute study.
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| Notes [1] - 4 subjects were randomised in this treatment arm. [2] - 4 subjects were randomised in this treatment arm. |
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Statistical analysis title |
Please see attached summary | ||||||||||||
Statistical analysis description |
as above
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Comparison groups |
Buspirone 0.20mg/kg and Placebo v Buspirone 0.10mg/kg and Placebo
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Number of subjects included in analysis |
8
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | ||||||||||||
P-value |
< 0.05 [4] | ||||||||||||
Method |
paired t-tests | ||||||||||||
Parameter type |
n/a | ||||||||||||
Confidence interval |
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| Notes [3] - please see attached summary [4] - 0.731 0.523 |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Adverse effects were reported immediately to the Principal Investigator and were assessed as minor adverse effects possibly related to the study procedures. Patients were all fine at the end of the clinical examinations and were discharged.
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Adverse event reporting additional description |
The PI and the clinician in charge decided not to treat any of these AEs as they were mild and released within a couple of hours without any treatment. In addition, all patients were contacted 24 hours afterwards and a week later. No further adverse events were reported.
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Assessment type |
Systematic | |||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
Local Imperial JRCO | |||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Buspirone 0.10mg/kg
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Reporting group description |
6 out of 8 reported mild drowsiness, fatigue and/or headache following the administration of the study drug. | |||||||||||||||
Reporting group title |
Buspirone 0.20mg/kg
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Reporting group description |
6 out of 8 reported mild drowsiness, fatigue and/or headache following the administration of the study drug. | |||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | ||||||||||||||||
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: 6 out of 8 reported mild drowsiness, fatigue and/or headache following the administration of the study drug. |
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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 May 2015 |
In this substantial amendment,
-details on blinding/unblining were included.
-further exclusion criteria were included.
-definitions of SAEs and SUSARs were refined to reflect local standard documentation. |
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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 | |||
