Clinical Trial Results:
The effect of bupropion in peripheral neuropathic pain. A randomized, double-blind, placebo-controlled study.
Summary
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EudraCT number |
2019-000243-27 |
Trial protocol |
DK |
Global end of trial date |
13 Oct 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Jan 2025
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First version publication date |
24 Jan 2025
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Other versions |
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 |
BUPROPION2019
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Odense University Hospital
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Sponsor organisation address |
J.B. Winløwsvej 4, Odense , Denmark, 5000
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Public contact |
Neuromuscular Clinic, Odense University Hospital, 0045 65412471, soeren.sindrup@rsyd.dk
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Scientific contact |
Neuromuscular Clinic, Odense University Hospital, 0045 65412471, soeren.sindrup@rsyd.dk
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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 |
04 Dec 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Oct 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Oct 2022
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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 objective is to determine if bupropion relieves peripheral neuropathic pain
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Protection of trial subjects |
None.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Apr 2019
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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 |
Denmark: 140
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Worldwide total number of subjects |
140
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EEA total number of subjects |
140
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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) |
92
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From 65 to 84 years |
48
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited from two counties (Region of Southern Denmark and Region Midt) in Denmark from 3 Sept. 2020 to 13 Oct. 2022. Patients were recruited from the outpatient clinic at the Department of Neurology at Odense University Hospital and Aarhus University, as well as from advertisement on Facebook. | |||||||||||||||||||||
Pre-assignment
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Screening details |
Most important inclusion criteria: Age ≥ 18 years, probable/definite peripheral neuropathic pain for at least 3 months, weekly average of daily pain intensity > 4 (0-10 NRS). Most important exclusion criteria: Other cause of pain, major depression within 6 months, treatment with antidepressants, opioids and drugs with potential interaction. | |||||||||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
140 | |||||||||||||||||||||
Number of subjects completed |
123 | |||||||||||||||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Consent withdrawn by subject: 5 | |||||||||||||||||||||
Reason: Number of subjects |
Comorbidity: 1 | |||||||||||||||||||||
Reason: Number of subjects |
Concomitant medication that could not be withdrawn: 1 | |||||||||||||||||||||
Reason: Number of subjects |
Enrolled in another study: 1 | |||||||||||||||||||||
Reason: Number of subjects |
Low pain score (NRS < 4): 4 | |||||||||||||||||||||
Reason: Number of subjects |
Other cause of pain in same area: 2 | |||||||||||||||||||||
Reason: Number of subjects |
Not neuropathic pain: 3 | |||||||||||||||||||||
Period 1
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Period 1 title |
Baseline
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Baseline to bupropion | |||||||||||||||||||||
Arm description |
Baseline period with no treatment before bupropion | |||||||||||||||||||||
Arm type |
Baseline no treatment | |||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Investigational medicinal product code |
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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 |
N/A
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Arm title
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Baseline to placebo | |||||||||||||||||||||
Arm description |
Baseline period with no treatment before placebo | |||||||||||||||||||||
Arm type |
Baseline no treatment | |||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Notes [1] - 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: Patients were excluded before baseline and allocation was started due to the reasons listed in the 'pre-assignment period'-section |
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Period 2
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Period 2 title |
Treatment periods summary
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Is this the baseline period? |
No | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||||||||||||||
Blinding implementation details |
Placebo capsules identical to terbutaline and imipramine capsules. Double-dummy technique.
Randomization was done by Sygehus Apotek Fyn using a computer-generated randomization list using block size unknown to the investigators
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Bupropion | |||||||||||||||||||||
Arm description |
Treatment with bupropion 150 mg to 300 mg daily. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Bupropion HCl retard
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Investigational medicinal product code |
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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 |
150 mg once a day for 1 week, followed by 150 mg twice a day for 5 weeks.
Age >= 75 years 150 mg a day for 6 weeks.
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
Treatment with placebo capsules | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo capsules
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Investigational medicinal product code |
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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 |
Dosage (number ogf capsules) corresponding to number of capsules with active substances
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Baseline to bupropion
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Reporting group description |
Baseline period with no treatment before bupropion | ||
Reporting group title |
Baseline to placebo
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Reporting group description |
Baseline period with no treatment before placebo | ||
Reporting group title |
Bupropion
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Reporting group description |
Treatment with bupropion 150 mg to 300 mg daily. | ||
Reporting group title |
Placebo
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Reporting group description |
Treatment with placebo capsules | ||
Subject analysis set title |
Intention to treat analysis
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
Modified intention to treat analysis set, subjects with data from 1 or 2 treatment periods
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End point title |
Numeric Rating of average daily pain (NRS), weekly median | ||||||||||||||||||||||||
End point description |
Average daily pain NRS score 0-10, 0 = no pain and 10 = worst possible pain.
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End point type |
Primary
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End point timeframe |
Weekly median of the average daily pain from the each of the 6 weeks in each treatment period and the 2 baseline periods were included in the analysis.
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Notes [1] - 4 subjects excluded due to missing data (no diary handed in), 1 subject too short datacollection [2] - 4 subjects excluded due to missing data (no diary handed in), 1 subject too short datacollection |
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Statistical analysis title |
Primary outcome in general linear model | ||||||||||||||||||||||||
Statistical analysis description |
General linear model Including bupropion treatment weeks 1-6 and corresponding baseline period compared to placebo treatment weeks 1-6 and corresponding baseline period in a cross-over design.
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Comparison groups |
Baseline to bupropion v Baseline to placebo v Bupropion v Placebo
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Number of subjects included in analysis |
236
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.005 | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
-0.45
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-0.76 | ||||||||||||||||||||||||
upper limit |
-0.14 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.16
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Adverse events information
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Timeframe for reporting adverse events |
After three weeks in each treatment period with bupropion and placebo. At the end of each treatment period. At the follow-up phone call at the end of study. Patients could contact the investigator via phone at any timepoint during the study period.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
Bupropion
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Reporting group description |
End of treatment with bupropion | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
End of treatment with 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? No | |||
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 |