Clinical Trial Results:
Interventional, randomized, double-blind, cross-over, placebo-controlled study to investigate the effects of nalmefene after single dose on the blood oxygen level dependent (BOLD) fMRI signal in the ventral striatum to reward responding in the monetary incentive delay task (MIDT), in non-treatment seeking subjects with alcohol dependence following alcohol challenge

Trial information Top of page
Trial identification
Sponsor protocol code	15660A
Additional study identifiers
ISRCTN number	-
US NCT number	NCT01969617
WHO universal trial number (UTN)	-
Other trial identifiers	HMR code: 13-506
Sponsors
Sponsor organisation name	H. Lundbeck A/S
Sponsor organisation address	Ottiliavej 9, Valby, Denmark,
Public contact	Lundbeck Clinical Trials, H Lundbeck A/S, LundbeckClinicalTrials@lundbeck.com
Scientific contact	Lundbeck Clinical Trials, H Lundbeck A/S, LundbeckClinicalTrials@lundbeck.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	30 Oct 2014
Is this the analysis of the primary completion data?	Yes
Primary completion date	30 Oct 2014
Global end of trial reached?	Yes
Global end of trial date	30 Oct 2014
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To investigate the effects of nalmefene after single dose on the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal in the ventral striatum to reward responding using the monetary incentive delay task (MIDT) task following alcohol clamp challenge.
Protection of trial subjects	The trial was conducted in accordance with the Declaration of Helsinki (2008) and ICH Good Clinical Practice (1996)
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	14 Jan 2014
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	United Kingdom: 22
Worldwide total number of subjects	22
EEA total number of subjects	22
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	22
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	The trial was conducted at one site in UK (single centre study)
Pre-assignment
Screening details	Subjects who met each of the inclusion and none of the exclusion criteria were eligible to participate in the study
Period 1
Period 1 title	overall trial (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator
Arms
Are arms mutually exclusive	Yes
Arm title	Selincro/Placebo
Arm description	Subjects were randomised to receive 18 mg Selincro (nalmefene) on Day 1 and matching placebo on Day 8. There was a washout period of at least 1 week between dosing/scanning days.
Arm type	Experimental
Investigational medicinal product name	Selincro
Investigational medicinal product code
Other name	Nalmefene
Pharmaceutical forms	Film-coated tablet
Routes of administration	Oral use
Dosage and administration details	Single dose of Selincro 18 mg, orally
Investigational medicinal product name	Placebo
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	Single dose, tablet, orally
Arm title	Placebo/Selincro
Arm description	Subjects were randomised to receive placebo on Day 1 and 18 mg Selincro (nalmefene)on Day 8. There was a washout period of at least 1 week between dosing/scanning days.
Arm type	Placebo
Investigational medicinal product name	Placebo
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	Single dose, tablet, orally
Investigational medicinal product name	Selincro
Investigational medicinal product code
Other name	Nalmefene
Pharmaceutical forms	Film-coated tablet
Routes of administration	Oral use
Dosage and administration details	Single dose of Selincro 18 mg, orally
Number of subjects in period 1 Selincro/Placebo Placebo/Selincro Started 11 11 Completed 11 10 Not completed 0 1      Adverse event, non-fatal - 1

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	overall trial
Reporting group description	-
Reporting group values overall trial Total Number of subjects 22 22 Age categorical Units: Subjects     In utero 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0     Newborns (0-27 days) 0 0     Infants and toddlers (28 days-23 months) 0 0     Children (2-11 years) 0 0     Adolescents (12-17 years) 0 0     Adults (18-64 years) 22 22     From 65-84 years 0 0     85 years and over 0 0 Gender categorical Units: Subjects     Female 0 0     Male 22 22 Race Units: Subjects     Asian 1 1     Black or African American 2 2     White 18 18     Other 1 1

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Selincro/Placebo
Reporting group description	Subjects were randomised to receive 18 mg Selincro (nalmefene) on Day 1 and matching placebo on Day 8. There was a washout period of at least 1 week between dosing/scanning days.
Reporting group title	Placebo/Selincro
Reporting group description	Subjects were randomised to receive placebo on Day 1 and 18 mg Selincro (nalmefene)on Day 8. There was a washout period of at least 1 week between dosing/scanning days.
Subject analysis set title	Selincro
Subject analysis set type	Full analysis
Subject analysis set description	18 mg Nalmefene
Subject analysis set title	Placebo
Subject analysis set type	Full analysis
Subject analysis set description	Placebo

End points Top of page

Primary: Blood oxygen level dependent (BOLD) fMRI signal in the ventral striatum to reward responding using the monetary incentive delay task (MIDT) task Top of page
End point title	Blood oxygen level dependent (BOLD) fMRI signal in the ventral striatum to reward responding using the monetary incentive delay task (MIDT) task
End point description
End point type	Primary
End point timeframe	4-6 hours after dosing
End point values Selincro Placebo Number of subjects analysed 18 18 Units: Percent change 16 25
Statistical analysis title	Reward respond signal (activity)
Statistical analysis description	The analysis was a paired t-test (a linear mixed-effects model, with subject as the random effect and drug condition as the fixed effect). Data were excluded in the MIDT for three sessions (head movement), so 18 subjects were included in the analysis
Comparison groups	Selincro v Placebo
Number of subjects included in analysis	36
Analysis specification	Pre-specified
Analysis type	other [1]
P-value	= 0.013
Method	Mixed models analysis
Confidence interval
Notes [1] - Mixed effect Model Repeat Measurement

Primary: Blood oxygen level dependent (BOLD) fMRI signal in the ventral striatum to reward responding using the monetary incentive delay task (MIDT) task Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	From dosing to end of study
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	16.1
Reporting groups
Reporting group title	Selincro
Reporting group description	-
Reporting group title	Placebo
Reporting group description	-
Serious adverse events Selincro Placebo Total subjects affected by serious adverse events      subjects affected / exposed 0 / 21 (0.00%) 0 / 22 (0.00%)      number of deaths (all causes) 0 0      number of deaths resulting from adverse events 0 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events Selincro Placebo Total subjects affected by non serious adverse events      subjects affected / exposed 10 / 21 (47.62%) 4 / 22 (18.18%) Vascular disorders Hot flush      subjects affected / exposed 2 / 21 (9.52%) 0 / 22 (0.00%)      occurrences all number 2 0 Nervous system disorders Headache      subjects affected / exposed 6 / 21 (28.57%) 0 / 22 (0.00%)      occurrences all number 6 0 Sinus Headache      subjects affected / exposed 1 / 21 (4.76%) 0 / 22 (0.00%)      occurrences all number 1 0 Somnolence      subjects affected / exposed 1 / 21 (4.76%) 0 / 22 (0.00%)      occurrences all number 1 0 General disorders and administration site conditions Chills      subjects affected / exposed 1 / 21 (4.76%) 0 / 22 (0.00%)      occurrences all number 1 0 Vessel Puncture Site Haematoma      subjects affected / exposed 1 / 21 (4.76%) 0 / 22 (0.00%)      occurrences all number 1 0 Catheter Site Pain      subjects affected / exposed 0 / 21 (0.00%) 1 / 22 (4.55%)      occurrences all number 0 1 Gastrointestinal disorders Nausea      subjects affected / exposed 4 / 21 (19.05%) 0 / 22 (0.00%)      occurrences all number 4 0 Vomiting      subjects affected / exposed 2 / 21 (9.52%) 0 / 22 (0.00%)      occurrences all number 2 0 Dyspepsia      subjects affected / exposed 0 / 21 (0.00%) 1 / 22 (4.55%)      occurrences all number 0 1 Skin and subcutaneous tissue disorders Dermatitis Allergic      subjects affected / exposed 0 / 21 (0.00%) 1 / 22 (4.55%)      occurrences all number 0 1 Psychiatric disorders Anxiety      subjects affected / exposed 0 / 21 (0.00%) 1 / 22 (4.55%)      occurrences all number 0 1

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

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