Clinical Trial Results:
A randomised, double-blind, parallel groups, placebo-controlled, multi-centre trial in oocyte donors assessing the effects of barusiban, a selective oxytocin antagonist, on uterine contractions on the day of embryo transfer

Trial information Top of page
Trial identification
Sponsor protocol code	FE 200440 CS11
Additional study identifiers
ISRCTN number	-
US NCT number	NCT01043120
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Ferring Pharmaceuticals A/S
Sponsor organisation address	Kay Fiskers Plads 11, Copenhagen S, Denmark, 2300
Public contact	Clinical Development Support, Ferring Pharmaceuticals, DK0-Disclosure@ferring.com
Scientific contact	Clinical Development Support, Ferring Pharmaceuticals, DK0-Disclosure@ferring.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	02 Dec 2010
Is this the analysis of the primary completion data?	Yes
Primary completion date	30 May 2010
Global end of trial reached?	Yes
Global end of trial date	02 Dec 2010
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To evaluate the effects of barusiban compared to placebo on uterine contractions on the day of embryo transfer.
Protection of trial subjects	The trial was performed in accordance with the Declaration of Helsinki and its amendments in force at the initiation of the trial.
Background therapy	An ultrasound contrast agent (SONOVUE) was used as non-investigational product (NIMP) during this trial. SONOVUE was administered intrauterinely via an embryo transfer catheter during the mock embryo transfer procedure.
Evidence for comparator	This was a randomised controlled trial with placebo as the comparator to adequately document the efficacy and safety of barusiban. A placebo group was justified for this trial as there is no therapy available for this indication.
Actual start date of recruitment	02 Feb 2010
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	Belgium: 23
Country: Number of subjects enrolled	Spain: 14
Country: Number of subjects enrolled	Czech Republic: 62
Worldwide total number of subjects	99
EEA total number of subjects	99
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)	99
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	A total of 4 sites randomised subjects into the trial : 1 in Belgium, 2 in Czech Republic, and 1 in Spain.
Pre-assignment
Screening details	A total of 102 subjects were screened in the trial, of whom 99 subjects were randomised: 49 to barusiban, and 50 to placebo.
Period 1
Period 1 title	Overall Period
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Data analyst, Assessor
Arms
Are arms mutually exclusive	Yes
Arm title	Barusiban
Arm description	Subjects randomised to barusiban investigational medicinal product (IMP) were included in this group.
Arm type	Experimental
Investigational medicinal product name	Barusiban
Investigational medicinal product code
Other name
Pharmaceutical forms	Solution for injection
Routes of administration	Intravenous use
Dosage and administration details	Subjects received barusiban (intravenous [IV] bolus 20 mg for 1 minute followed by an IV infusion of 19 mg for up to 59 minutes). The maximum total duration of administration was 60 minutes.
Arm title	Placebo
Arm description	Subjects randomised to placebo IMP were included in this group.
Arm type	Placebo
Investigational medicinal product name	Placebo
Investigational medicinal product code
Other name
Pharmaceutical forms	Solution for injection
Routes of administration	Intravenous use
Dosage and administration details	Subjects received IV bolus of saline (sodium chloride 0.9%) for 1 minute followed by an IV infusion of saline for up to 59 minutes.
Number of subjects in period 1 Barusiban Placebo Started 49 50 Completed 48 50 Not completed 1 0      Adverse event, non-fatal 1 -

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Barusiban
Reporting group description	Subjects randomised to barusiban investigational medicinal product (IMP) were included in this group.
Reporting group title	Placebo
Reporting group description	Subjects randomised to placebo IMP were included in this group.
Reporting group values Barusiban Placebo Total Number of subjects 49 50 99 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) 49 50 99     From 65-84 years 0 0 0     85 years and over 0 0 0 Gender categorical Units: Subjects     Female 49 50 99     Male 0 0 0
Subject analysis sets
Subject analysis set title	Intention-to-treat (ITT)
Subject analysis set type	Intention-to-treat
Subject analysis set description	All randomised and exposed subjects were included in this analysis set.
Subject analysis set title	Per protocol (PP) analysis set
Subject analysis set type	Per protocol
Subject analysis set description	All the subjects in the ITT analysis set except those who met any of the criteria considered as major protocol deviations were included in this analysis set.
Subject analysis set title	Safety analysis set
Subject analysis set type	Safety analysis
Subject analysis set description	All randomised and exposed subjects were included in this analysis set.
Subject analysis sets values Intention-to-treat (ITT) Per protocol (PP) analysis set Safety analysis set Number of subjects 99 78 99 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) 99 78 99     From 65-84 years 0 0 0     85 years and over 0 0 0 Age continuous Units: years     arithmetic mean (standard deviation) ( ) ( ) ( ) Gender categorical Units: Subjects     Female 99 78 99     Male 0 0 0

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Barusiban
Reporting group description	Subjects randomised to barusiban investigational medicinal product (IMP) were included in this group.
Reporting group title	Placebo
Reporting group description	Subjects randomised to placebo IMP were included in this group.
Subject analysis set title	Intention-to-treat (ITT)
Subject analysis set type	Intention-to-treat
Subject analysis set description	All randomised and exposed subjects were included in this analysis set.
Subject analysis set title	Per protocol (PP) analysis set
Subject analysis set type	Per protocol
Subject analysis set description	All the subjects in the ITT analysis set except those who met any of the criteria considered as major protocol deviations were included in this analysis set.
Subject analysis set title	Safety analysis set
Subject analysis set type	Safety analysis
Subject analysis set description	All randomised and exposed subjects were included in this analysis set.

End points Top of page

Primary: Absolute change from Baseline in frequency of uterine contractions at 30 minutes after start of dosing Top of page
End point title	Absolute change from Baseline in frequency of uterine contractions at 30 minutes after start of dosing
End point description	Data are presented for the ITT analysis set.
End point type	Primary
End point timeframe	From Baseline to 30 minutes after start of dosing.
End point values Barusiban Placebo Number of subjects analysed 38 40 Units: contractions/min     arithmetic mean (standard deviation) -0.25 ( 1.52 ) 0.47 ( 1.26 )
Statistical analysis title	Frequency at 30 minutes - barusiban vs placebo
Statistical analysis description	Analysis of change in contraction frequency from Baseline at 30 minutes was done using analysis of covariance (ANCOVA) on the ITT analysis set.
Comparison groups	Barusiban v Placebo
Number of subjects included in analysis	78
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.014
Method	t-test, 2-sided
Parameter type	Mean difference (final values)
Point estimate	-0.58
Confidence interval
level	95%
sides	2-sided
lower limit	-1.04
upper limit	-0.12

Primary: Absolute change from Baseline in frequency of uterine contractions at 30 minutes after start of dosing Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	Overall Treatment Period
Adverse event reporting additional description	Treatment-emergent adverse events (TEAEs) were presented and evaluated by treatment groups. Data were presented for safety analysis set.
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	12.1
Reporting groups
Reporting group title	Barusiban
Reporting group description	Subjects randomised to barusiban IMP were included in this group.
Reporting group title	Placebo
Reporting group description	Subjects randomised to placebo IMP were included in this group.
Serious adverse events Barusiban Placebo Total subjects affected by serious adverse events      subjects affected / exposed 0 / 49 (0.00%) 0 / 50 (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: 0%
Non-serious adverse events Barusiban Placebo Total subjects affected by non serious adverse events      subjects affected / exposed 1 / 49 (2.04%) 2 / 50 (4.00%) Nervous system disorders Presyncope      subjects affected / exposed 1 / 49 (2.04%) 0 / 50 (0.00%)      occurrences all number 1 0 Gastrointestinal disorders Abdominal pain      subjects affected / exposed 0 / 49 (0.00%) 1 / 50 (2.00%)      occurrences all number 0 1 Reproductive system and breast disorders Ovarian torsion      subjects affected / exposed 0 / 49 (0.00%) 1 / 50 (2.00%)      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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