Clinical Trial Results:
UNTERSUCHUNG DER GENETISCH BEDINGTEN VARIABILITÄT DES OPIOID- UND OPIATBEDARFS IM RAHMEN DES DROGENSUBSTITUTIONSPROGRAMMS und HÄUFIGKEITEN GENETISCHER POLYMORPHISMEN BEI POPULATIONEN MIT UND OHNE OPIOIDABHÄNGIGKEITSERKRANKUNG (STUDIENTEIL B)

Trial information Top of page
Trial identification
Sponsor protocol code	7108
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Medical University Innsbruck
Sponsor organisation address	Christoph-Probst-Platz 1, Innrain 52, Innsbruck, Austria, 6020
Public contact	Dr.in med. univ. Beate Beer-Sandner, Bezirkshauptmannschaft Kufstein, Bozner Platz 1 6330 Kufstein , +43 5372 606 6144, bh.ku.gesundheitswesen@tirol.gv.at
Scientific contact	Dr.in med. univ. Beate Beer-Sandner, Bezirkshauptmannschaft Kufstein, Bozner Platz 1 6330 Kufstein , +43 5372 606 6144, bh.ku.gesundheitswesen@tirol.gv.at
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 Apr 2013
Is this the analysis of the primary completion data?	Yes
Primary completion date	30 Apr 2013
Global end of trial reached?	Yes
Global end of trial date	31 Dec 2020
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	The major aim of the present study was to identify genetic polymorphisms contributing to the individual susceptibility to opioid addiction and to replicate earlier findings in this regard, respectively.
Protection of trial subjects	Only DNA samples were taken. DNA samples of all participants were obtained via buccal swabs.
Background therapy	There was no background therapy.
Evidence for comparator	There was no evidence for a comparator.
Actual start date of recruitment	28 Aug 2008
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	Austria: 284
Worldwide total number of subjects	284
EEA total number of subjects	284
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)	284
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	For the presented candidate gene association study, a total of 148 unrelated opioid dependent individuals undergoing opioid maintenance treatment were recruited at the drug addiction outpatient clinic of the Innsbruck Medical University. In total, 142 of the 148 recruited patients and all 142 healthy control subjects were included in the study.
Pre-assignment
Screening details	Following inclusion criteria were applied: written informed consent; opioid dependence according to the DSM-IV criteria; opioid maintenance therapy with either methadone or buprenorphine; history of at least 2 years of daily heroin (and/or morphine) use.
Period 1
Period 1 title	Sample collection (overall period)
Is this the baseline period?	Yes
Allocation method	Not applicable
Blinding used	Not blinded
Arms
Are arms mutually exclusive	Yes
Arm title	Outpatients
Arm description	-
Arm type	Experimental
Investigational medicinal product name	Buprenorphine hydrochloride
Investigational medicinal product code
Other name
Pharmaceutical forms	Sublingual tablet
Routes of administration	Sublingual use
Dosage and administration details	A total of 142 unrelated opioid dependent individuals undergoing opioid maintenance treatment were enrolled in the study. Each patient was treated individually.
Investigational medicinal product name	Methadone hydrochloride
Investigational medicinal product code
Other name
Pharmaceutical forms	Oral liquid
Routes of administration	Oral use
Dosage and administration details	A total of 142 unrelated opioid dependent individuals undergoing opioid maintenance treatment were enrolled in the study. Each patient was treated individually.
Arm title	Control
Arm description	-
Arm type	No intervention
Investigational medicinal product name	No investigational medicinal product assigned in this arm
Number of subjects in period 1 Outpatients Control Started 142 142 Completed 142 142

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Outpatients
Reporting group description	-
Reporting group title	Control
Reporting group description	-
Reporting group values Outpatients Control Total Number of subjects 142 142 284 Age categorical Units: Subjects     In utero 0 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0 0     Newborns (0-27 days) 0 0 0     Infants and toddlers (28 days-23 months) 0 0 0     Children (2-11 years) 0 0 0     Adolescents (12-17 years) 0 0 0     Adults (18-64 years) 142 142 284     From 65-84 years 0 0 0     85 years and over 0 0 0 Age continuous Units: years     arithmetic mean (standard deviation) 31 ( 8 ) 29 ( 6 ) - Gender categorical Units: Subjects     Female 45 61 106     Male 97 81 178

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Outpatients
Reporting group description	-
Reporting group title	Control
Reporting group description	-

End points Top of page

Primary: GAL, rs948854 (GG genotype) Top of page
End point title	GAL, rs948854 (GG genotype)
End point description	Analysis of homozygous carriers of the minor allele (GG genotype) .
End point type	Primary
End point timeframe	Day 1
End point values Outpatients Control Number of subjects analysed 142 142 Units: number 18 4
Statistical analysis title	GAL, rs948854 (GG genotype)
Comparison groups	Outpatients v Control
Number of subjects included in analysis	284
Analysis specification	Pre-specified
Analysis type	other
P-value	= 0.002 [1]
Method	t-test, 2-sided
Parameter type	Odds ratio (OR)
Point estimate	5.01
Confidence interval
level	95%
sides	2-sided
lower limit	1.54
upper limit	18
Notes [1] - Homozygous carriers of the minor allele (GG genotype) were significantly more prevalent in the patient group (p = 0.002, χ2 = 9.657, df = 1).

Primary: GAL, rs948854 (GG genotype) Top of page

Primary: OPRD1, rs223686 (TT genotype) Top of page
End point title	OPRD1, rs223686 (TT genotype)
End point description	Analysis of homozygous carriers of the minor allele (TT genotype) .
End point type	Primary
End point timeframe	Day 1
End point values Outpatients Control Number of subjects analysed 142 142 Units: number 3 13
Statistical analysis title	OPRD1, rs223686 (TT genotype)
Comparison groups	Outpatients v Control
Number of subjects included in analysis	284
Analysis specification	Pre-specified
Analysis type	other
P-value	= 0.018
Method	t-test, 2-sided
Parameter type	Odds ratio (OR)
Point estimate	0.21
Confidence interval
level	95%
sides	2-sided
lower limit	0.05
upper limit	0.83

Primary: OPRD1, rs223686 (TT genotype) Top of page

Adverse events Top of page
Adverse events information [1]
Timeframe for reporting adverse events	Day 1
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	CTCAE
Dictionary version	4.03
Reporting groups
Reporting group title	Outpatients
Reporting group description	-
Reporting group title	Control
Reporting group description	-
Serious adverse events Outpatients Control Total subjects affected by serious adverse events      subjects affected / exposed 0 / 142 (0.00%) 0 / 142 (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 Outpatients Control Total subjects affected by non serious adverse events      subjects affected / exposed 0 / 142 (0.00%) 0 / 142 (0.00%)
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: As only a buccal swab was performed, no AEs and SAEs were reported.

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
Online references
http://www.ncbi.nlm.nih.gov/pubmed/24086514

More information Top of page