Clinical Trial Results:
A randomised, placebo-controlled, double-blind, parallel groups, multinational, multicentre trial assessing the effect of barusiban administered subcutaneously on the day of transfer on implantation and pregnancy rates in IVF/ICSI patients.
Summary
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EudraCT number |
2012-001622-10 |
Trial protocol |
BE CZ ES PL |
Global end of trial date |
28 Apr 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Aug 2018
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First version publication date |
05 Aug 2016
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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 |
000048
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01723982 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Ferring Pharmaceuticals A/S
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Sponsor organisation address |
Kay Fiskers Plads 11, Copenhagen S, Denmark, 2300
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Public contact |
Clinical Development Support, Ferring Pharmaceuticals, DK0-Disclosure@ferring.com
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Scientific contact |
Clinical Development Support, Ferring Pharmaceuticals, DK0-Disclosure@ferring.com
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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 |
08 Jul 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Oct 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Apr 2015
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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 evaluate the effect of barusiban compared to placebo on implantation rate in in-vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) patients.
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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.
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Background therapy |
Vaginal progesterone tablets (LUTINUS/ENDOMETRIN, Ferring Pharmaceuticals) 100 mg twice daily were provided for luteal phase support from the day after oocyte retrieval and until the day of the clinical pregnancy visit. On the day of transfer, subjects inserted the progesterone tablets at least 3 hours before transfer and at least 3 hours after transfer. Progesterone support could be terminated earlier than the clinical pregnancy visit in case of a negative beta unit of human chorionic gonadotropin (βhCG) test or menses. | ||
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 |
14 Nov 2012
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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 |
Australia: 8
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Country: Number of subjects enrolled |
Canada: 12
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Country: Number of subjects enrolled |
Poland: 33
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Country: Number of subjects enrolled |
Spain: 85
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Country: Number of subjects enrolled |
Belgium: 60
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Country: Number of subjects enrolled |
Czech Republic: 57
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Worldwide total number of subjects |
255
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EEA total number of subjects |
235
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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) |
255
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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 |
The participating subjects were recruited among the patients attending the clinics. A total of 12 sites randomised subjects into the trial : 1 in Australia, 2 in Belgium, 1 in Canada, 1 in Czech Republic, 1 in Poland and 6 in Spain. | |||||||||||||||
Pre-assignment
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Screening details |
A total of 363 subjects were screened in the trial, of whom 255 subjects were randomised: 130 to barusiban and 125 to placebo. | |||||||||||||||
Period 1
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Period 1 title |
Randomisation to End-of-Trial (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, Data analyst, Carer | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Barusiban | |||||||||||||||
Arm description |
Subjects randomised to barusiban IMP were included in this group. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Barusiban
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
The barusiban IMP was a 20 mg/mL isotonic solution in acetate buffer. The 1st IMP administration of barusiban 40 mg subcutaneously (SC) was 45 min prior to transfer and 2nd administration of barusiban 10 mg SC was 60 min after the 1st administration.
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Arm title
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Placebo | |||||||||||||||
Arm description |
Subjects randomised to placebo IMP were included in this group. | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
The placebo IMP was an isotonic acetate buffer solution. The 1st administration of isotonic acetate buffer SC was 45 min prior to transfer and 2nd administration of isotonic acetate buffer SC was 60 min after the 1st administration.
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Baseline characteristics reporting groups
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Reporting group title |
Barusiban
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Reporting group description |
Subjects randomised to barusiban IMP were included in this group. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects randomised to placebo IMP were included in this group. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Barusiban
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Reporting group description |
Subjects randomised to barusiban IMP were included in this group. | ||
Reporting group title |
Placebo
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Reporting group description |
Subjects randomised to placebo IMP were included in this group. | ||
Subject analysis set title |
Intention-to-Treat (ITT) Analysis Set
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The ITT analysis set was defined as all randomised subjects.
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Subject analysis set title |
Per-Protocol (PP) Analysis Set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The PP analysis set was defined as all randomised and exposed subjects except those excluded as a result of major protocol deviations.
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Subject analysis set title |
Safety Analysis Set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety analysis set was defined as all randomised and exposed subjects.
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End point title |
Ongoing Implantation Rate | ||||||||||||
End point description |
Ongoing implantation rate was defined as the number of viable fetuses 10-11 weeks after transfer divided by the number of embryos/blastocysts transferred. Data are presented for the ITT analysis set.
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End point type |
Primary
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End point timeframe |
10-11 weeks after transfer.
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Notes [1] - Number of embryos/blastocysts = 225 [2] - Number of embryos/blastocysts = 215 |
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Statistical analysis title |
Adjusted Ongoing Implantation Rate | ||||||||||||
Statistical analysis description |
Analysis of hypothesis of ‘equal effect’ against the alternative of ‘different effect’ between the probability that an embryo/blastocyst would implant in the barusiban and placebo groups.
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Comparison groups |
Barusiban v Placebo
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Number of subjects included in analysis |
255
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Analysis specification |
Pre-specified
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Analysis type |
superiority [3] | ||||||||||||
P-value |
= 0.663 [4] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
1.11
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.69 | ||||||||||||
upper limit |
1.78 | ||||||||||||
Notes [3] - Comparison between the groups was based on logistic regression model with treatment, trial site, primary reason for infertility, and embryo/blastocyst quality as factors. [4] - p-value corresponds to a two-sided test of superiority. |
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End point title |
Ongoing Implantation Rate - Transfer Day 3 | ||||||||||||
End point description |
Ongoing implantation rate was analysed for subjects with transfer on day 3. Data are presented for the ITT analysis set.
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End point type |
Primary
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End point timeframe |
10-11 weeks after transfer.
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Notes [5] - Number of embryos transferred = 117 [6] - Number of embryos transferred = 111 |
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Statistical analysis title |
Adjusted Ongoing Implantation Rate-Transfer Day 3 | ||||||||||||
Statistical analysis description |
Analysis of ongoing implantation rate in subjects with transfer on day 3.
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Comparison groups |
Barusiban v Placebo
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Number of subjects included in analysis |
127
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Analysis specification |
Pre-specified
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Analysis type |
superiority [7] | ||||||||||||
P-value |
= 0.227 [8] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
0.628
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.3 | ||||||||||||
upper limit |
1.34 | ||||||||||||
Notes [7] - Comparison between the groups was based on logistic regression model with treatment, number of embryos transferred, trial site, and primary reason for infertility as factors. [8] - p-value corresponds to a two-sided test of superiority. |
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End point title |
Ongoing Implantation Rate - Transfer Day 5 | ||||||||||||
End point description |
Ongoing implantation rate was analysed for subjects with transfer on day 5. Data are presented for the ITT analysis set.
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End point type |
Primary
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End point timeframe |
10-11 weeks after transfer.
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Notes [9] - Number of blastocysts transferred = 108 [10] - Number of blastocysts transferred = 104 |
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Statistical analysis title |
Adjusted Ongoing Implantation Rate-Transfer Day 5 | ||||||||||||
Statistical analysis description |
Analysis of ongoing implantation rate in subjects with transfer on day 5.
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Comparison groups |
Barusiban v Placebo
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Number of subjects included in analysis |
128
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Analysis specification |
Pre-specified
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Analysis type |
superiority [11] | ||||||||||||
P-value |
= 0.022 [12] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
2.337
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.13 | ||||||||||||
upper limit |
4.84 | ||||||||||||
Notes [11] - Comparison between the groups was based on logistic regression model with treatment, number of blastocysts transferred, trial site, primary reason for infertility, and blastocyst quality parameters as factors. [12] - p-value corresponds to a two-sided test of superiority. |
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End point title |
Ongoing Pregnancy Rate | ||||||||||||
End point description |
Ongoing pregnancy was defined as at least one intrauterine viable fetus 10-11 weeks after transfer. Data are presented for the ITT analysis set.
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End point type |
Secondary
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End point timeframe |
10-11 weeks after transfer.
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Statistical analysis title |
Adjusted Ongoing Pregnancy Rate | ||||||||||||
Statistical analysis description |
Analysis of ongoing pregnancy rate was intended to provide supportive evidence of treatment effect of barusiban.
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Comparison groups |
Barusiban v Placebo
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Number of subjects included in analysis |
255
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Analysis specification |
Pre-specified
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Analysis type |
superiority [13] | ||||||||||||
P-value |
= 0.897 [14] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
0.963
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.54 | ||||||||||||
upper limit |
1.71 | ||||||||||||
Notes [13] - Comparison between the groups was based on logistic regression model with treatment, trial site, primary reason for infertility, and embryo/blastocyst quality as factors. [14] - p-value corresponds to a two-sided test of superiority. |
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End point title |
Ongoing Pregnancy Rate - Transfer Day 3 | ||||||||||||
End point description |
Ongoing pregnancy was analysed for subjects with transfer on day 3. Data are presented for the ITT analysis set.
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End point type |
Secondary
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End point timeframe |
10-11 weeks after transfer.
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Statistical analysis title |
Adjusted Ongoing Pregnancy Rate- Transfer Day 3 | ||||||||||||
Statistical analysis description |
Analysis of ongoing pregnancy rate in subjects with transfer on day 3.
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Comparison groups |
Barusiban v Placebo
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Number of subjects included in analysis |
127
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Analysis specification |
Pre-specified
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Analysis type |
superiority [15] | ||||||||||||
P-value |
= 0.219 [16] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
0.557
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.22 | ||||||||||||
upper limit |
1.42 | ||||||||||||
Notes [15] - Comparison between the groups was based on logistic regression model with treatment, number of embryos transferred, trial site, and primary reason for infertility as factors. [16] - p-value corresponds to a two-sided test of superiority. |
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End point title |
Ongoing Pregnancy Rate - Transfer Day 5 | ||||||||||||
End point description |
Ongoing pregnancy was analysed for subjects with transfer on day 5. Data are presented for the ITT analysis set.
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End point type |
Secondary
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End point timeframe |
10-11 weeks after transfer.
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Statistical analysis title |
Adjusted Ongoing Pregnancy Rate- Transfer Day 5 | ||||||||||||
Statistical analysis description |
Analysis of ongoing pregnancy rate in subjects with transfer on day 5.
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Comparison groups |
Barusiban v Placebo
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Number of subjects included in analysis |
128
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Analysis specification |
Pre-specified
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Analysis type |
superiority [17] | ||||||||||||
P-value |
= 0.147 [18] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
1.967
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.79 | ||||||||||||
upper limit |
4.9 | ||||||||||||
Notes [17] - Comparison between the groups was based on logistic regression model with treatment, number of blastocysts transferred, trial site, primary reason for infertility, and blastocyst quality parameters as factors. [18] - p-value corresponds to a two-sided test of superiority. |
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End point title |
Implantation Rate | ||||||||||||
End point description |
Implantation rate was defined as the number of intrauterine gestational sacs with fetal heart beat (5-6 weeks after transfer) divided by the number of embryos/blastocysts transferred. Data are presented for the ITT analysis set.
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End point type |
Secondary
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End point timeframe |
5-6 weeks after transfer.
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Notes [19] - Number of embryos/blastocysts = 225 [20] - Number of embryos/blastocysts = 215 |
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Statistical analysis title |
Adjusted Implantation Rate | ||||||||||||
Statistical analysis description |
Analysis of implantation rate was intended to provide supportive evidence of treatment effect of barusiban.
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Comparison groups |
Barusiban v Placebo
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Number of subjects included in analysis |
255
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Analysis specification |
Pre-specified
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Analysis type |
superiority [21] | ||||||||||||
P-value |
= 0.546 [22] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
1.154
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.73 | ||||||||||||
upper limit |
1.83 | ||||||||||||
Notes [21] - Comparison between the groups was based on logistic regression model with treatment, trial site, primary reason for infertility, and embryo/blastocyst quality as factors. [22] - p-value corresponds to a two-sided test of superiority. |
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End point title |
Implantation Rate - Transfer Day 3 | ||||||||||||
End point description |
Implantation rate was analysed for subjects with transfer on day 3. Data are presented for the ITT analysis set.
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End point type |
Secondary
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End point timeframe |
5-6 weeks after transfer.
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Notes [23] - Number of embryos transferred = 117 [24] - Number of embryos transferred = 111 |
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Statistical analysis title |
Adjusted Implantation Rate - Transfer Day 3 | ||||||||||||
Statistical analysis description |
Analysis of implantation rate in subjects with transfer on day 3.
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Comparison groups |
Barusiban v Placebo
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Number of subjects included in analysis |
127
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Analysis specification |
Pre-specified
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Analysis type |
superiority [25] | ||||||||||||
P-value |
= 0.251 [26] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
0.65
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.31 | ||||||||||||
upper limit |
1.35 | ||||||||||||
Notes [25] - Comparison between the groups was based on logistic regression model with treatment, number of embryos transferred, trial site, and primary reason for infertility as factors. [26] - p-value corresponds to a two-sided test of superiority. |
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End point title |
Implantation Rate - Transfer Day 5 | ||||||||||||
End point description |
Implantation rate was analysed for subjects with transfer on day 5. Data are presented for the ITT analysis set.
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End point type |
Secondary
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End point timeframe |
5-6 weeks after transfer.
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Notes [27] - Number of blastocysts transferred = 108 [28] - Number of blastocysts transferred = 104 |
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Statistical analysis title |
Adjusted Implantation Rate - Transfer Day 5 | ||||||||||||
Statistical analysis description |
Analysis of implantation rate in subjects with transfer on day 5.
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Comparison groups |
Barusiban v Placebo
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Number of subjects included in analysis |
128
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Analysis specification |
Pre-specified
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Analysis type |
superiority [29] | ||||||||||||
P-value |
= 0.013 [30] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
2.471
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.21 | ||||||||||||
upper limit |
5.06 | ||||||||||||
Notes [29] - Comparison between the groups was based on logistic regression model with treatment, number of blastocysts transferred, trial site, primary reason for infertility, and blastocyst quality parameters as factors. [30] - p-value corresponds to a two-sided test of superiority. |
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End point title |
Clinical Pregnancy with Fetal Heart Beat Rate | ||||||||||||
End point description |
Clinical pregnancy with fetal heart beat was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer. Data are presented for the ITT analysis set.
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End point type |
Secondary
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End point timeframe |
5-6 weeks after transfer.
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Statistical analysis title |
Adj. Clinical Pregnancy with Fetal Heart Beat Rate | ||||||||||||
Statistical analysis description |
Analysis of clinical pregnancy with fetal heart beat rate was intended to provide supportive evidence of treatment effect of barusiban.
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Comparison groups |
Barusiban v Placebo
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Number of subjects included in analysis |
255
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Analysis specification |
Pre-specified
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Analysis type |
superiority [31] | ||||||||||||
P-value |
= 0.882 [32] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
1.044
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Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.59 | ||||||||||||
upper limit |
1.83 | ||||||||||||
Notes [31] - Comparison between the groups was based on logistic regression model with treatment, trial site, primary reason for infertility, and embryo/blastocyst quality as factors. [32] - p-value corresponds to a two-sided test of superiority. |
|
|||||||||||||
End point title |
Clinical Pregnancy with Fetal Heart Beat Rate - Transfer Day 3 | ||||||||||||
End point description |
Clinical pregnancy with fetal heart beat rate was analysed for subjects with transfer on day 3. Data are presented for the ITT analysis set.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
5-6 weeks after transfer.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adj. Clin. Pregnancy with Fetal Heart Beat Rate | ||||||||||||
Statistical analysis description |
Analysis of clinical pregnancy with fetal heart beat rate in subjects with transfer on day 3.
|
||||||||||||
Comparison groups |
Barusiban v Placebo
|
||||||||||||
Number of subjects included in analysis |
127
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [33] | ||||||||||||
P-value |
= 0.254 [34] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
0.592
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.24 | ||||||||||||
upper limit |
1.46 | ||||||||||||
Notes [33] - Comparison between the groups was based on logistic regression model with treatment, number of embryos transferred, trial site, and primary reason for infertility as factors. [34] - p-value corresponds to a two-sided test of superiority. |
|
|||||||||||||
End point title |
Clinical Pregnancy with Fetal Heart Beat Rate - Transfer Day 5 | ||||||||||||
End point description |
Clinical pregnancy with fetal heart beat rate was analysed for subjects with transfer on day 5. Data are presented for the ITT analysis set.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
5-6 weeks after transfer.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adj. Clin. Pregnancy with Fetal Heart Beat Rate | ||||||||||||
Statistical analysis description |
Analysis of clinical pregnancy with fetal heat beat rate in subjects with transfer on day 5.
|
||||||||||||
Comparison groups |
Barusiban v Placebo
|
||||||||||||
Number of subjects included in analysis |
128
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [35] | ||||||||||||
P-value |
= 0.074 [36] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
2.29
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.92 | ||||||||||||
upper limit |
5.68 | ||||||||||||
Notes [35] - Comparison between the groups was based on logistic regression model with treatment, number of blastocysts transferred, trial site, primary reason for infertility, and blastocyst quality parameters as factors. [36] - p-value corresponds to a two-sided test of superiority. |
|
|||||||||||||
End point title |
Positive βhCG Rate | ||||||||||||
End point description |
Positive βhCG was confirmed by a blood test 13-15 days after transfer. Data are presented for the ITT analysis set.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
13-15 days after transfer.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted Positive βhCG Rate | ||||||||||||
Statistical analysis description |
Analysis of positive βhCG rate was intended to provide supportive evidence of treatment effect of barusiban.
|
||||||||||||
Comparison groups |
Barusiban v Placebo
|
||||||||||||
Number of subjects included in analysis |
255
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [37] | ||||||||||||
P-value |
= 0.612 [38] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
1.154
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.66 | ||||||||||||
upper limit |
2 | ||||||||||||
Notes [37] - Comparison between the groups was based on logistic regression model with treatment, trial site, primary reason for infertility, and embryo/blastocyst quality as factors. [38] - p-value corresponds to a two-sided test of superiority. |
|
|||||||||||||
End point title |
Positive βhCG Rate - Transfer Day 3 | ||||||||||||
End point description |
Positive βhCG rate was analysed for subjects with transfer on day 3. Data are presented for the ITT analysis set.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
13-15 days after transfer.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted Positive βhCG Rate - Transfer Day 3 | ||||||||||||
Statistical analysis description |
Analysis of positive βhCG rate in subjects with transfer on day 3.
|
||||||||||||
Comparison groups |
Barusiban v Placebo
|
||||||||||||
Number of subjects included in analysis |
127
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [39] | ||||||||||||
P-value |
= 0.313 [40] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
0.658
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.29 | ||||||||||||
upper limit |
1.48 | ||||||||||||
Notes [39] - Comparison between the groups was based on logistic regression model with treatment, number of embryos transferred, trial site, and primary reason for infertility as factors. [40] - p-value corresponds to a two-sided test of superiority. |
|
|||||||||||||
End point title |
Positive βhCG Rate - Transfer Day 5 | ||||||||||||
End point description |
Positive βhCG rate was analysed for subjects with transfer on day 5. Data are presented for the ITT analysis set.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
13-15 days after transfer.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted Positive βhCG Rate - Transfer Day 5 | ||||||||||||
Statistical analysis description |
Analysis of positive βhCG rate in subjects with transfer on day 5.
|
||||||||||||
Comparison groups |
Barusiban v Placebo
|
||||||||||||
Number of subjects included in analysis |
128
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [41] | ||||||||||||
P-value |
= 0.077 [42] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
2.29
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.91 | ||||||||||||
upper limit |
5.73 | ||||||||||||
Notes [41] - Comparison between the groups was based on logistic regression model with treatment, number of blastocysts transferred, trial site, primary reason for infertility, and blastocyst quality parameters as factors. [42] - p-value corresponds to a two-sided test of superiority. |
|
|||||||||
End point title |
Barusiban Concentration [43] | ||||||||
End point description |
The plasma concentration of barusiban at the expected tmax was analysed. Data are presented for the ITT analysis set.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
30 minutes after the 2nd IMP administration.
|
||||||||
Notes [43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results for this endpoint is only reported for the barusiban group since barusiban was not administered in the placebo group. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Injection Site Reactions | ||||||||||||||||||
End point description |
Presence and intensity (none, mild, moderate or severe) of redness, pain, itching, swelling and bruising was assessed by the investigator directly or by asking the subject, as applicable. Data are presented for the safety analysis set.
The numbers presented refer to number of subjects with at least one mild/moderate/severe reaction (out of a total of 20 assessments per subject).
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Injection site reactions were assessed immediately and 30 min after each IMP administration (i.e. post-1st IMP and post-2nd IMP).
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events were recorded from signing of informed consent to the end-of-trial.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Adverse events with onset after start of the first IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
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 |