Clinical Trial Results:
Follow-Up Study to Assess Long-Term Safety and Outcomes in Infants and Children Born to Mothers Participating in Retosiban Treatment Studies
Summary
|
|
EudraCT number |
2014-000499-24 |
Trial protocol |
BE GB ES SE DE IT FR |
Global end of trial date |
02 Sep 2019
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
12 Jul 2020
|
First version publication date |
23 May 2020
|
Other versions |
v1 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
200722
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
GlaxoSmithKline
|
||
Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
|
||
Public contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
|
||
Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-001359-PIP01-12 | ||
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 |
11 Mar 2020
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
02 Sep 2019
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
The study objective is to assess the safety and outcomes in infants and children who were exposed to retosiban or comparator in the Phase III treatment studies.
|
||
Protection of trial subjects |
To minimize inconvenience to parents of the infants enrolled, this study did not require medical interventions or study visits to an investigational site. Instead, parents or legal guardians were prompted at certain timepoints to complete developmental questionnaires and other data regarding their child’s health status via an electronic device.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jun 2015
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
24 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Belgium: 5
|
||
Country: Number of subjects enrolled |
Italy: 5
|
||
Country: Number of subjects enrolled |
Sweden: 3
|
||
Country: Number of subjects enrolled |
Germany: 6
|
||
Country: Number of subjects enrolled |
Mexico: 22
|
||
Country: Number of subjects enrolled |
Korea, Republic of: 12
|
||
Country: Number of subjects enrolled |
Israel: 32
|
||
Country: Number of subjects enrolled |
United Kingdom: 3
|
||
Country: Number of subjects enrolled |
United States: 4
|
||
Country: Number of subjects enrolled |
Japan: 6
|
||
Worldwide total number of subjects |
98
|
||
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) |
4
|
||
Infants and toddlers (28 days-23 months) |
94
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
|||||||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||||||
Recruitment details |
This was a randomized, long-term follow-up study to evaluate the safety and outcomes of infants and children born to women who received retosiban or comparator in the Phase III spontaneous preterm labor (SPTL) treatment studies:200719 (NCT02377466) and 200721 (NCT02292771). Current study was referred as a retosiban infant outcome study (ARIOS). | ||||||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||||||
Screening details |
A total of 101 participants were screened and 98 participants were enrolled and randomized in this study. | ||||||||||||||||||||||||
Period 1
|
|||||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer | ||||||||||||||||||||||||
Arms
|
|||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||
Arm title
|
Placebo (200719 study) | ||||||||||||||||||||||||
Arm description |
All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous [IV] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site. | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Placebo was available as 0.9 percent sodium chloride infusion matched for retosiban volume, intravenous (IV) loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment.
|
||||||||||||||||||||||||
Arm title
|
Atosiban (200721 study) | ||||||||||||||||||||||||
Arm description |
All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram [mg] using atosiban 6.75 mg per 0.9 milliliter [mL] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Atosiban
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Atosiban was available as an initial bolus dose of 6.75 milligram (mg) using 6.75 mg per 0.9 milliliter (mL) solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using 37.5 mg per 5 mL concentrate for solution.
|
||||||||||||||||||||||||
Arm title
|
Retosiban (200719 and 200721 study) | ||||||||||||||||||||||||
Arm description |
All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Retosiban
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Retosiban was available as 6 mg IV loading dose over 5 minutes followed by a 6 milligram per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period
|
||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo (200719 study)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous [IV] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Atosiban (200721 study)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram [mg] using atosiban 6.75 mg per 0.9 milliliter [mL] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Retosiban (200719 and 200721 study)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Placebo (200719 study)
|
||
Reporting group description |
All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous [IV] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site. | ||
Reporting group title |
Atosiban (200721 study)
|
||
Reporting group description |
All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram [mg] using atosiban 6.75 mg per 0.9 milliliter [mL] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site. | ||
Reporting group title |
Retosiban (200719 and 200721 study)
|
||
Reporting group description |
All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site. |
|
|||||||||||||
End point title |
Number of infants and children with newly diagnosed chronic medical conditions (after 28 days post estimated date of delivery) [1] | ||||||||||||
End point description |
The parents of the infants filled in an online child health inventory (CHI) questionnaire, which asked them about each condition. If they reported anything, it was then verified by a healthcare professional. ARIOS Safety Population was a subset of the Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study. Number of infants and children with newly diagnosed chronic medical conditions are presented.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
From 28 days post estimated date of delivery up to 24 months
|
||||||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
Notes [2] - ARIOS Safety Population [3] - ARIOS Safety Population [4] - ARIOS Safety Population |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Number of infants and children with newly diagnosed congenital anomalies (after 28 days post estimated date of delivery) [5] | ||||||||||||||||||||
End point description |
A congenital anomaly is a condition present at birth that results from malformation, deformation, or disruption in 1 or more parts of the body, a chromosomal abnormality, or a known clinical syndrome. Congenital anomaly serious adverse events (SAEs) were examined by the birth defect evaluator. Events were coded per centers for disease control and prevention (CDC) Metropolitan Atlanta congenital defects program (MACDP) criteria and/or European surveillance of congenital anomalies (EUROCAT) criteria. Predefined defect codes specified whether the defect was face and neck, a cleft lip or palate, cardiovascular, respiratory, upper gastrointestinal, female genitalia, male genitalia, renal and urinary system, other musculoskeletal defects, skin, a chromosome anomaly, other organ systems, or a specified syndrome. Number of infants and children with newly diagnosed congenital anomalies reported up to 1 year of chronological age and reported after 1 year of chronological age are presented.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
From 28 days post estimated date of delivery up to 24 months
|
||||||||||||||||||||
Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||
|
|||||||||||||||||||||
Notes [6] - ARIOS Safety Population [7] - ARIOS Safety Population [8] - ARIOS Safety Population |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of infant and child death (after 28 days post estimated date of delivery) [9] | ||||||||||||
End point description |
Number of infant and child death that occurred after 28 days post estimated date of delivery and up to 24 months are presented.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
From 28 days post estimated date of delivery up to 24 months
|
||||||||||||
Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
Notes [10] - ARIOS Safety Population [11] - ARIOS Safety Population [12] - ARIOS Safety Population |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of infants with ages and stages questionnaire-3 (ASQ-3) score in the black zone for any domain at 9 months [13] | ||||||||||||
End point description |
The ASQ-3 included 6 questions in each area, designed to assess: communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes(10 points), sometimes(5 points) or not yet(0 points) to each question to complete ASQ-3. At 9 months, the pre-defined cut-off score for communication was 13.97,gross motor was 17.82,fine motor was 31.32, problem solving was 28.72 and personal social skills was 18.91. Total score was derived by taking mean of all 5 components. Any infant who scored below the cut-off,a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for any domains in the black zone at 9 months is presented. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
At 9 months
|
||||||||||||
Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
Notes [14] - ARIOS Safety Population [15] - ARIOS Safety Population [16] - ARIOS Safety Population |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of infants with ages and stages questionnaire-3 (ASQ-3) score in the black zone for any domain at 18 months [17] | ||||||||||||
End point description |
The ASQ-3 included 6 questions in each area, designed to assess: communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes(10 points), sometimes(5 points) or not yet(0 points) to each question to complete ASQ-3. At 18 months, the pre-defined cut-off score for communication was 13.06,gross motor was 37.38,fine motor was 34.32, problem solving was 25.74 and personal social skills was 27.19. Total score was derived by taking mean of all 5 components. Any infant who scored below the cut-off,a score more than or equal to 2 standard deviations below the mean score(that is Black zone in the score chart)in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for any domains in the black zone at 18 months is presented. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
At 18 months
|
||||||||||||
Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
Notes [18] - ARIOS Safety Population [19] - ARIOS Safety Population [20] - ARIOS Safety Population |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of infants with ages and stages questionnaire-3 (ASQ-3) score in the black zone for any domain at 24 months [21] | ||||||||||||
End point description |
The ASQ-3 included 6 questions in each area, designed to assess: communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes(10 points), sometimes(5 points) or not yet(0 points) to each question to complete ASQ-3. At 24 months, the pre-defined cut-off score for communication was 25.17,gross motor was 38.07,fine motor was 35.16, problem solving was 29.78 and personal social skills was 31.54. Total score was derived by taking mean of all 5 components. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score(that is Black zone in the score chart)in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for any domains in the black zone at 24 months is presented. Only those participants with data available at the specified data points were analyzed
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
At 24 months
|
||||||||||||
Notes [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
Notes [22] - ARIOS Safety Population [23] - ARIOS Safety Population [24] - ARIOS Safety Population |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of infants with ages and stages questionnaire-3 (ASQ-3) score in the black zone for gross motor skills [25] | ||||||||||||||||||||||||
End point description |
The ASQ-3 included 6 questions in each area; communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 9 months, the pre-defined cut-off score for gross motor skills was 17.82. At 18 months, it was 37.38. At 24 months, it was 38.07. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist. Number of infants with ASQ-3 scores for gross motor skills in the black zone at 9, 18 and 24 months is presented. All 98 participants in the study were included in the analysis (5, 44 and 49 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
9, 18 and 24 months
|
||||||||||||||||||||||||
Notes [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [26] - ARIOS Safety Population [27] - ARIOS Safety Population [28] - ARIOS Safety Population |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of infants with ages and stages questionnaire-3 (ASQ-3) score in the black zone for fine motor skills [29] | ||||||||||||||||||||||||
End point description |
The ASQ-3 included 6 questions in each area; communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 9 months, the pre-defined cut-off score for fine motor skills was 31.32. At 18 months, it was 34.32. At 24 months, it was 35.16. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist. Number of infants with ASQ-3 scores for fine motor skills in the black zone at 9, 18 and 24 months is presented. All 98 participants in the study were included in the analysis (5, 44 and 49 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
9, 18 and 24 months
|
||||||||||||||||||||||||
Notes [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [30] - ARIOS Safety Population [31] - ARIOS Safety Population [32] - ARIOS Safety Population |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of infants with ages and stages questionnaire-3 (ASQ-3) score in the black zone for communication skills [33] | ||||||||||||||||||||||||
End point description |
The ASQ-3 included 6 questions in each area; communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 9 months, the pre-defined cut-off score for communication skills was 13.97. At 18 months, it was 13.06. At 24 months, it was 25.17. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist. Number of infants with ASQ-3 scores for communication skills in the black zone at 9, 18 and 24 months is presented. All 98 participants in the study were included in the analysis (5, 44 and 49 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
9, 18 and 24 months
|
||||||||||||||||||||||||
Notes [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [34] - ARIOS Safety Population [35] - ARIOS Safety Population [36] - ARIOS Safety Population |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of infants with ages and stages questionnaire-3 (ASQ-3) score in the black zone for problem solving skills [37] | ||||||||||||||||||||||||
End point description |
The ASQ-3 included 6 questions in each area; communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 9 months, the pre-defined cut-off score for problem solving skills was 28.72. At 18 months, it was 25.74. At 24 months, it was 29.78. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist. Number of infants with ASQ-3 scores for problem solving skills in the black zone at 9, 18 and 24 months is presented. All 98 participants in the study were included in the analysis (5, 44 and 49 Participants),but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
9, 18 and 24 months
|
||||||||||||||||||||||||
Notes [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [38] - ARIOS Safety Population [39] - ARIOS Safety Population [40] - ARIOS Safety Population |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of infants with ages and stages questionnaire-3 (ASQ-3) score in the black zone for personal social skills [41] | ||||||||||||||||||||||||
End point description |
The ASQ-3 included 6 questions in each area; communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 9 months, the pre-defined cut-off score for personal social skills was 18.91. At 18 months, it was 27.19. At 24 months, it was 31.54. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist. Number of infants with ASQ-3 scores for personal social skills in the black zone at 9, 18 and 24 months is presented. All 98 participants in the study were included in the analysis (5, 44 and 49 Participants),but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
9, 18 and 24 months
|
||||||||||||||||||||||||
Notes [41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [42] - ARIOS Safety Population [43] - ARIOS Safety Population [44] - ARIOS Safety Population |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of infants referred for developmental evaluation using Bayley scales of infant development, third edition (BSID-III) [45] | ||||||||||||||||||||||||
End point description |
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 Standard Deviations (SDs) below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was evaluated using the BSID-III. It scaled scores for cognitive, language (receptive and expressive), motor (fine and gross motor). The language and motor areas each have a composite score, with a mean of 100, a SD of 15 and a range of 40 to 160. Scores lower than 70 indicated moderate or severe impairment. In the cognitive area, the infant scored "1" if they could do an activity and "0" if they could not. Total score was derived by taking mean of all the components. Number of infants referred for developmental evaluation using BSID-III is presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
9, 18 and 24 months
|
||||||||||||||||||||||||
Notes [45] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [46] - ARIOS Safety Population [47] - ARIOS Safety Population [48] - ARIOS Safety Population |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of infants with Bayley Scales of Infant Development, third edition score greater than 2 standard deviation below the mean score for the cognitive scale (less than 4) [49] | ||||||||||||||||||||||||
End point description |
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 Standard Deviations (SDs) below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was evaluated using the BSID-III. It scaled scores for cognitive, language (receptive and expressive), motor (fine and gross motor). The language and motor areas each have a composite score, with a mean of 100, a SD of 15 and a range of 40 to 160. Scores lower than 70 indicated moderate or severe impairment. In the cognitive area, the infant scored "1" if they could do an activity and "0" if they could not. Number of infants with BSID-III score greater than 2 SD below the mean score for the cognitive scale (less than 4) is presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
9, 18 and 24 months
|
||||||||||||||||||||||||
Notes [49] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [50] - ARIOS Safety Population [51] - ARIOS Safety Population [52] - ARIOS Safety Population |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of infants with Bayley Scales of Infant Development, third edition score greater than 2 standard deviation below the mean score for the gross motor scale (less than 4) [53] | ||||||||||||||||||||||||
End point description |
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 Standard Deviations (SDs) below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was evaluated using the BSID-III. It scaled scores for cognitive, language (receptive and expressive), motor (fine and gross motor). The language and motor areas each have a composite score, with a mean of 100, a SD of 15 and a range of 40 to 160. Scores lower than 70 indicated moderate or severe impairment. In the cognitive area, the infant scored "1" if they could do an activity and "0" if they could not. Number of infants with BSID-III score greater than 2 SD below the mean score for the gross motor scale (less than 4) is presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
9, 18 and 24 months
|
||||||||||||||||||||||||
Notes [53] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [54] - ARIOS Safety Population [55] - ARIOS Safety Population [56] - ARIOS Safety Population |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of infants with Bayley Scales of Infant Development, third edition score greater than 2 standard deviation below the mean score for the fine motor scale (less than 4) [57] | ||||||||||||||||||||||||
End point description |
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 Standard Deviations (SDs) below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was evaluated using the BSID-III. It scaled scores for cognitive, language (receptive and expressive), motor (fine and gross motor). The language and motor areas each have a composite score, with a mean of 100, a SD of 15 and a range of 40 to 160. Scores lower than 70 indicated moderate or severe impairment. In the cognitive area, the infant scored "1" if they could do an activity and "0" if they could not. Number of infants with BSID-III score greater than 2 SD below the mean score for the fine motor scale (less than 4) is presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
9, 18 and 24 months
|
||||||||||||||||||||||||
Notes [57] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [58] - ARIOS Safety Population [59] - ARIOS Safety Population [60] - ARIOS Safety Population |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of infants with Bayley Scales of Infant Development, third edition score greater than 2 standard deviation below the mean score for the language scale (less than 70) [61] | ||||||||||||||||||||||||
End point description |
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 Standard Deviations (SDs) below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was evaluated using the BSID-III. It scaled scores for cognitive, language (receptive and expressive), motor (fine and gross motor). The language and motor areas each have a composite score, with a mean of 100, a SD of 15 and a range of 40 to 160. Scores lower than 70 indicated moderate or severe impairment. In the cognitive area, the infant scored "1" if they could do an activity and "0" if they could not. Number of infants with BSID-III score greater than 2 SD below the mean score for the language scale (less than 70) is presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
9, 18 and 24 months
|
||||||||||||||||||||||||
Notes [61] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [62] - ARIOS Safety Population [63] - ARIOS Safety Population [64] - ARIOS Safety Population |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of infants with a child behavior checklist for ages 1.5 to 5 years (CBCL/1.5 to 5) score above the 97th percentile for a subset of prespecified questions that relate to attention and hyperactivity problems [65] | ||||||||||||
End point description |
The CBCL/1.5 to 5 questionnaire is a parent-completed questionnaire used for assessing behavioral and social competencies. It included approximately 100 items that characterized preschool children between the ages of 1.5 and 5 years. Each question could be answered as “not true scored as"0",somewhat or sometimes true scored as"1"or very true or often true scored as "2”. There were 6 questions related to attention and hyperactivity problems. The responses to those 6 questions were summed (ranged 0 to 12). Total score of 0 to 9 indicated normal,10 indicated borderline and 11 to 12 indicated significant attention and hyperactivity problems. Scores above the 97th percentile are in the significant range of clinical concern. Number of infants with CBCL/1.5 to 5 score above 97th percentile for subset of pre-specified questions related to attention and hyperactivity problems at 24 months is reported. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
At 24 months
|
||||||||||||
Notes [65] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
Notes [66] - ARIOS Safety Population [67] - ARIOS Safety Population [68] - ARIOS Safety Population |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Number of infants indicated as needing further evaluation after completion of the modified checklist for autism in toddlers- revised with follow-up (M-CHAT-R/F) [69] | ||||||||||||||||||||
End point description |
The M-CHAT-R/F is a parent-reported autism screening tool designed to identify children 16 to 30 months of age who received a more thorough assessment for possible early signs of autism spectrum disorder (ASD) or developmental delay. The M-CHAT-R/F consisted of 20 questions that were answered with either “yes, scored as 0” or “no, scored as 1”. Total scores (ranged 0 to 20) on the M-CHAT-R/F between 0 and 2 indicated a low risk, scores between 3 and 7 indicated a medium risk and triggered administration of the follow-up questionnaire, and scores between 8 and 20 indicated a high risk. Number of infants who needed further evaluation as per the M-CHAT-R/F at 18 and 24 months is presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
18 and 24 months
|
||||||||||||||||||||
Notes [69] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||
|
|||||||||||||||||||||
Notes [70] - ARIOS Safety Population [71] - ARIOS Safety Population [72] - ARIOS Safety Population |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of infants referred for neurological evaluation to determine diagnosis of cerebral palsy [73] | ||||||||||||
End point description |
Parents reported in CHI questionnaire if their infant had cerebral palsy. If the infant was not diagnosed with cerebral palsy, then this was detected as part of the ASQ-3 assessment, based on the results of the gross motor scale. To confirm the diagnosis of cerebral palsy, the healthcare practitioner referred the infant for further neurological tests if they scored in the black zone of the ASQ-3 at the month 24 assessment. Number of infants referred for neurological evaluation to determine diagnosis of cerebral palsy at 24 months is presented. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
At 24 months
|
||||||||||||
Notes [73] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
Notes [74] - ARIOS Safety Population [75] - ARIOS Safety Population [76] - ARIOS Safety Population |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Number of infants with the indicators of neurodevelopmental impairment [77] | ||||||||||||||||||||||||||||||||||||
End point description |
The indicators of neurodevelopmental impairment were 'hearing impaired, uncorrected even with aids'; 'blindness in 1 or both eyes, or sees light only'; 'cerebral palsy-moderate and severe (moderate: Grade 2 or 3 using the gross motor functional classification system [GMFCS] and severe: Grade 4 or 5 using the GMFCS)'; 'cognitive impairment: BSID-III cognitive scale score of less than 2 SDs below mean score (less than 4)'; 'motor impairment: BSID-III motor composite scale score of greater than 2 SDs below mean score (less than 70)'; 'diagnosis of ASD, attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD)'. Number of infants having any 1 of these indicators is presented. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to 24 months
|
||||||||||||||||||||||||||||||||||||
Notes [77] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [78] - ARIOS Safety Population [79] - ARIOS Safety Population [80] - ARIOS Safety Population |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information [1]
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo (200719 study)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous [IV] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Atosiban (200721 study)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram [mg] using atosiban 6.75 mg per 0.9 milliliter [mL] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Retosiban (200719 and 200721 study)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
17 Aug 2015 |
Amendment 01: Extended the study duration from 24 months to 5 years; added an assessment using a modified version of the child health inventory questionaire; added an additional assessment of modified checklist for autism in toddlers- revised with follow-up (M-CHAT-R/F); revised child behavior checklist (CBCl/1.5 to 5) per American academy of pediatrics guidelines, deletion of neurodevelopment endpoint for an additional behaviour assessment using M-CHAT-R/F and CBCl/1.5 to 5; revised the subgroups to reflect study design of Phase III spontaneous preterm labour Study 200719 (NEWBORN-1); clarified unblinding text; incorporation of other administrative changes |
||
01 Nov 2018 |
Amendment 02: Reduction of study duration from 5 years to 24 months; termination of retosiban development program; low recruitment for 200719 (NEWBORN-1) and 200721 (ZINN) studies; modification in the recommendation of independent data monitoring committee; reclassification of all resource utilization endpoints as exploratory endpoints due to the reduced sample size; correction of an error in the mean Bayley Scales of Infant Development, third edition (BSID-III) score; incorporation of other administrative changes |
||
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 |