Clinical Trial Results:
Double-blind, placebo-controlled randomised study on the efficacy of naloxone nasal spray for the treatment of gambling disorder
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Summary
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EudraCT number |
2017-001946-93 |
Trial protocol |
FI |
Global end of trial date |
16 Oct 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
28 May 2022
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First version publication date |
28 May 2022
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Other versions |
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Summary report(s) |
NalGamb synopsis |
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 |
NalGamb
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03430180 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Finnish Institute for Health and Welfare
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Sponsor organisation address |
PL 30, Mannerheimintie 166, Helsinki, Finland, 00271
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Public contact |
Clinical Trial Information, Finnish Institute of Health and Welfare, 358 9295248124, sari.castren@thl.fi
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Scientific contact |
Clinical Trial Information, Finnish Institute of Health and Welfare, 0295248525 9295248124, sari.castren@thl.fi
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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 |
20 Sep 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
16 Oct 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Oct 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 |
To determine whether treatment with naloxone hydrochloride nasal spray reduces gambling urge symptoms in patients with gambling disorder.
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Protection of trial subjects |
Adverse events were monitored daily via e-diary, when detected, participants were contacted, advised and referred, if needed, to appropriate care.
Well being of the participants were carefully monitored and assessed in all contact points screening, bl, week 3, week 6, week 9 and week 12 appointments with highly trained clinical team and follow up call was taken place at week 14.
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Background therapy |
All participants received psychosocial support regardless of the treatment group. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Nov 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Finland: 126
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Worldwide total number of subjects |
126
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EEA total number of subjects |
126
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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) |
126
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were recruited through advertising online and in newspa- pers directing them to the study website where potential study partici- pants completed the South Oaks Gambling Screen-Revised (SOGS-R; Abbott & Volberg, 1996) test as an online pre-screening assessment. | |||||||||||||||
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Pre-assignment
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Screening details |
2.4.1. Screening Clinic visit: Informed consent was obtained. After initial screening assessments, eligible participants repeated the SOGS-R test and were assessed for gambling craving (G-SAS, VAS), gambling severity (PGSI, NODS, DSM-5), internet use (IDS9-SF), QoL (EUROHIS-8) alcohol con- sumption (AUDIT), smoking and depression (MADRS) and clini | |||||||||||||||
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Period 1
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Period 1 title |
Baseline (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 | |||||||||||||||
Blinding implementation details |
The study was double-blinded, so neither the investigator nor subject knew the treatment to which a particular group the subject had been randomised.
The randomisation , labelling and packaging of IMP were undertaken nu an independent contractor and so investigator, data management and statistics personel were blinded to treatment allocation. IMP for both treatment groups were provided in identical nasal sprays. Permuted block randomisation sequence (1:1 ratio 2 treatment arms).
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Naloxone | |||||||||||||||
Arm description |
Participants were randomised on a 1:1 basis to receive either the naloxone hydrochloride nasal spray or a matching placebo spray. | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Naloxone hydrocholoride nasal spay
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation vapour
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Routes of administration |
Intranasal use
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Dosage and administration details |
Participants were instructed to administer the investigational me- dicinal product (IMP) nasally, 1 spray (0.1 mL 4 mg) into 1 nostril up to 4 times per day (maximum daily dose: 16 mg) as needed in response to a gambling urge or when the likelihood of gambling was considered high, for 12 weeks.
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Arm title
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Plasebo | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Plasebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray
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Routes of administration |
Intranasal use
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Dosage and administration details |
Participants were instructed to administer the investigational me-
dicinal product (IMP) nasally, 1 spray (0.1 mL = 4 mg) into 1 nostril up
to 4 times per day (maximum daily dose: 16 mg) as needed in response
to a gambling urge or when the likelihood of gambling was considered
high, for 12 weeks.
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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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Subject analysis sets
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Subject analysis set title |
demographic and baseline characteristics
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The participants were on average 45 years old (within the group’s overall age range of 18 to 75 years). Approximately 70% (n 88) of the subjects were males. The majority of participants were Caucasians (n 125, 99%). There were no notable differences in demographics between the treatment groups (Table 3).
Sixty-eight participants (54%) were married or cohabiting. Most participants lived either alone (n 52, 41%) or with their family (n 71, 56%). Participants were mainly employed as office workers or clerks (n 69, 55%), and 30 participants (24%) had retired. Almost all par- ticipants (n 115, n 91%) reported that they currently consumed alcohol and 56 participants (44%) were current smokers. The proportion of current smokers was higher in the IN naloxone group (55%) as compared to the placebo group (34%).
No participant was excluded due the risk of suicide or suicidal ideation (C-SSRS). Both groups were on average equally ready and motivated for change as measured on a 10 cm VAS scal
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End points reporting groups
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Reporting group title |
Naloxone
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Reporting group description |
Participants were randomised on a 1:1 basis to receive either the naloxone hydrochloride nasal spray or a matching placebo spray. | ||
Reporting group title |
Plasebo
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Reporting group description |
- | ||
Subject analysis set title |
demographic and baseline characteristics
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The participants were on average 45 years old (within the group’s overall age range of 18 to 75 years). Approximately 70% (n 88) of the subjects were males. The majority of participants were Caucasians (n 125, 99%). There were no notable differences in demographics between the treatment groups (Table 3).
Sixty-eight participants (54%) were married or cohabiting. Most participants lived either alone (n 52, 41%) or with their family (n 71, 56%). Participants were mainly employed as office workers or clerks (n 69, 55%), and 30 participants (24%) had retired. Almost all par- ticipants (n 115, n 91%) reported that they currently consumed alcohol and 56 participants (44%) were current smokers. The proportion of current smokers was higher in the IN naloxone group (55%) as compared to the placebo group (34%).
No participant was excluded due the risk of suicide or suicidal ideation (C-SSRS). Both groups were on average equally ready and motivated for change as measured on a 10 cm VAS scal
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End point title |
G-SAS, Gambling Assessment Scale | |||||||||
End point description |
The Gambling Assessment Scale (G-SAS; Kim et al., 2001; Kim et al., 2009).
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End point type |
Primary
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End point timeframe |
From baseline to week 12
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Attachments |
A scatterplot of G-SAS total score values from Bas |
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Statistical analysis title |
Statistical analysis | |||||||||
Statistical analysis description |
The primary endpoint G-SAS total score was modelled by the linear mixed-effects model. The effect of treatment and time factors were tested by the likelihood ratio test. Similarly, the linear mixed-effects model analysis was performed for total scores of second endpoint vari- ables. Each separate G-SAS variable was also modelled by the proportional-odds cumulative logit mixed model with use of the ordinal package in R software 4.0.5. Multivariate repeated measures analysis for G-SAS variables
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Comparison groups |
Naloxone v Plasebo
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Number of subjects included in analysis |
126
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||
P-value |
< 0.001 | |||||||||
Method |
Mixed models analysis | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Confidence interval |
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level |
95% | |||||||||
sides |
1-sided
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lower limit |
- | |||||||||
upper limit |
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| Notes [1] - he primary endpoint G-SAS total score was modelled by the linear mixed-effects model. The effect of treatment and time factors were tested by the likelihood ratio test. Similarly, the linear mixed-effects model analysis was performed for total scores of second endpoint vari- ables. Each separate G-SAS variable was also modelled by the proportional-odds cumulative logit mixed model with use of the ordinal package in R software 4.0.5. Multivariate repeated measures analysis for G-SAS variab |
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End point title |
VAS (craving) | |||||||||
End point description |
Visual analogue scale (VAS) (gambling craving) from Baseline to Week 3, 6, 9 and 12.
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End point type |
Secondary
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End point timeframe |
Visual analogue scale (VAS) (gambling craving) from Baseline to Week 3, 6, 9 and 12.
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| No statistical analyses for this end point | ||||||||||
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End point title |
PGSI | |||||||||
End point description |
Gambling severity (Problem Gambling Severity Index [PGSI]) from Baseline to Week 6 and 12
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End point type |
Secondary
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End point timeframe |
Gambling severity (Problem Gambling Severity Index [PGSI]) from Baseline to Week 6 and 12
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Attachments |
A scatterplot of PGSI total score values from Base |
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Statistical analysis title |
Statistical Analysis | |||||||||
Statistical analysis description |
The primary endpoint G-SAS total score was modelled by the linear mixed-effects model. The effect of treatment and time factors were tested by the likelihood ratio test. Similarly, the linear mixed-effects model analysis was performed for total scores of second endpoint vari- ables. Each separate G-SAS variable was also modelled by the proportional-odds cumulative logit mixed model with use of the ordinal package in R software 4.0.5. Multivariate repeated measures analysis for G-SAS variables wa
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Comparison groups |
Naloxone v Plasebo
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Number of subjects included in analysis |
126
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
< 0.01 | |||||||||
Method |
Mixed models analysis | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
- | |||||||||
upper limit |
- | |||||||||
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End point title |
DSM-5 | |||||||||
End point description |
Gambling severity (Diagnostic and Statistical Manual for Mental Disorders, 5th edition [DSM-5]) from Baseline to Week 6 and 12
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End point type |
Secondary
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End point timeframe |
Gambling severity (Diagnostic and Statistical Manual for Mental Disorders, 5th edition [DSM-5]) from Baseline to Week 6 and 12
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| No statistical analyses for this end point | ||||||||||
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End point title |
NODS | |||||||||
End point description |
Gambling problems (National Opinion Research Centre DSM Screen for Gambling Problems [NODS]) from Baseline to Week 3, 6, 9 and 12
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End point type |
Secondary
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End point timeframe |
Gambling problems (National Opinion Research Centre DSM Screen for Gambling Problems [NODS]) from Baseline to Week 3, 6, 9 and 12
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| No statistical analyses for this end point | ||||||||||
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End point title |
Gambling expenditure | ||||||||||||
End point description |
Gambling expenditure and frequency from Baseline to Week 12 (eDiary)
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End point type |
Secondary
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End point timeframe |
Gambling expenditure and frequency from Baseline to Week 12 (eDiary)
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Attachments |
A scatterplot of natural logarithm values of gambl |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
GASS | |||||||||
End point description |
Abstinence of gambling (Gambling Abstinence Self-Efficacy Scale [GASS]) from
Baseline to Week 3, 6, 9 and 12.
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End point type |
Secondary
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End point timeframe |
Abstinence of gambling (Gambling Abstinence Self-Efficacy Scale [GASS]) from
Baseline to Week 3, 6, 9 and 12.
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| No statistical analyses for this end point | ||||||||||
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End point title |
IDS-9SF | |||||||||
End point description |
Internet use (Internet Disorder Scale-9 Short Form [IDS-9 SF]) from Baseline to Week 6 and 12.
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End point type |
Secondary
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End point timeframe |
Internet use (Internet Disorder Scale-9 Short Form [IDS-9 SF]) from Baseline to Week 6 and 12.
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Attachments |
A scatterplot of IDS total score values from Basel |
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| No statistical analyses for this end point | ||||||||||
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End point title |
QoL | |||||||||
End point description |
QoL (World Health Organization European Health Interview Survey for QoL [WHO: EUROHIS-8]) from Baseline to Week 6 and 12.
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End point type |
Secondary
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End point timeframe |
QoL (World Health Organization European Health Interview Survey for QoL [WHO: EUROHIS-8]) from Baseline to Week 6 and 12.
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Attachments |
A scatterplot of Quality of Life total score valu |
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| No statistical analyses for this end point | ||||||||||
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End point title |
AUDIT | |||||||||
End point description |
Alcohol consumption (Alcohol Use Disorders Identification Test [AUDIT]) from Baseline to Week 6 and 12
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End point type |
Secondary
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End point timeframe |
Alcohol consumption (Alcohol Use Disorders Identification Test [AUDIT]) from Baseline to Week 6 and 12
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Attachments |
A scatterplot of AUDIT total score values from |
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| No statistical analyses for this end point | ||||||||||
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End point title |
smoking | ||||||||||||
End point description |
Smoking from Screening to Week 12
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End point type |
Secondary
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End point timeframe |
Smoking from Screening to Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Madrs | |||||||||
End point description |
Depression (Montgomery-Asberg Depression Rating Scale [MADRS]) from Baseline to Week 6 and 12
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End point type |
Secondary
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End point timeframe |
Depression (Montgomery-Asberg Depression Rating Scale [MADRS]) from Baseline to Week 6 and 12
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Attachments |
A scatterplot of MADRS total score values from Ba |
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| No statistical analyses for this end point | ||||||||||
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End point title |
safety end points | ||||||||||||
End point description |
Number and proportion of subjects with adverse events (AEs) Assessment of clinical laboratory parameters from Baseline to Week 12 Assessment of vital signs from Baseline to Week 6 and 12
Assessment of physical examination from Baseline to Week 12 Assessment of body weight from Baseline to Week 12
Assessment of examination of nasal mucosa from Baseline to Week 6 and Assessment of smell test from Baseline to Week 12
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End point type |
Secondary
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End point timeframe |
Number and proportion of subjects with adverse events (AEs) Assessment of clinical laboratory parameters from Baseline to Week 12 Assessment of vital signs from Baseline to Week 6 and 12
Assessment of physical examination from Baseline to Week 12 Assessm
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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 |
diary was used to gather any adverse events - diary was followed daily basis.
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Adverse event reporting additional description |
The study eDiary was used to record changes in participant health status and was reviewed via each participant’s eDiary during their visit. The severity of each adverse event (AE) was to be characterised and then classified into 1 of the following 3 categories by the Investigator: Mild: The AE did not interfere in a significant manner with the subj
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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 |
1
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Reporting groups
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Reporting group title |
Naloxone
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Reporting group description |
- | ||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||
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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 | |||
