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Follow up Study to Assess Long Term Safety and Outcomes in Infants and Children Born to Mothers Participating in Retosiban Treatment Studies (ARIOS)

Primary Purpose

Obstetric Labour, Premature

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Retosiban
Atosiban
Placebo
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obstetric Labour, Premature focused on measuring infants, retosiban, Preterm Labor, long-term safety follow-up

Eligibility Criteria

10 Weeks - 20 Weeks (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Mother is randomly assigned and dosed (retosiban or comparator) in 1 of the Phase III SPTL retosiban clinical studies.
  • Infant is alive at 28 days post EDD.
  • Written informed consent is obtained from the parent(s) or legal guardian(s) of the infant. The parent/legal guardian of subjects aged 12 to 17 years must also provide written agreement for the infant to participate in the study where required by applicable regulatory and country or state requirements.

Exclusion Criteria:

  • There are no formal exclusion criteria for participation.

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Active Comparator

Arm Label

Placebo (200719 study)

Retosiban (200719 and 200721 study)

Atosiban (200721 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 will not require any medical interventions or study visits to an investigational site.

All infants and children born to women who received retosiban (6 milligram [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 will not require any medical interventions or study visits to an investigational site.

All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 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 will not require any medical interventions or study visits to an investigational site.

Outcomes

Primary Outcome Measures

Number of Infants and Children With Newly Diagnosed Chronic Medical Conditions (After 28 Days Post Estimated Date of Delivery)
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. Number of infants and children with newly diagnosed chronic medical conditions are presented.
Number of Infants and Children With Newly Diagnosed Congenital Anomalies (After 28 Days Post Estimated Date of Delivery)
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.
Number of Infant and Child Death (After 28 Days Post Estimated Date of Delivery)
Number of infant and child death that occurred after 28 days post estimated date of delivery and up to 24 months are presented.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Any Domain at 9 Months
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Any Domain at 18 Months
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Any Domain at 24 Months
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Gross Motor Skills
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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, the pre-defined cut-off score for gross motor skills was 37.38. At 24 months, the pre-defined cut-off score for gross motor skills 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 for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for gross motor skills in the black zone at 9, 18 and 24 months is presented.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Fine Motor Skills
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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, the pre-defined cut-off score for fine motor skills was 34.32. At 24 months, the pre-defined cut-off score for fine motor skills 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 for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for fine motor skills in the black zone at 9, 18 and 24 months is presented.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Communication Skills
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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, the pre-defined cut-off score for communication skills was 13.06. At 24 months, the pre-defined cut-off score for communication skills 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 for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for communication skills in the black zone at 9, 18 and 24 months is presented.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Problem Solving Skills
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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, the pre-defined cut-off score for problem solving skills was 25.74. At 24 months, the pre-defined cut-off score for problem solving skills 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 for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for problem solving skills in the black zone at 9, 18 and 24 months is presented.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Personal Social Skills
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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, the pre-defined cut-off score for personal social skills was 27.19. At 24 months, the pre-defined cut-off score for personal social skills 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 for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for personal social skills in the black zone at 9, 18 and 24 months is presented.
Number of Infants Referred for Developmental Evaluation Using Bayley Scales of Infant Development, Third Edition (BSID-III)
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 referred to a developmental specialist for a neurodevelopmental evaluation 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.
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)
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 SDs below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation 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.
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)
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 SDs below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation 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.
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)
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 SDs below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation 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.
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)
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 SDs below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation 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.
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
The CBCL/1.5 to 5 questionnaire is a parent-completed questionnaire used for assessing behavioral problems and social competencies. It included approximately 100 items that described specific kinds of behavioral, emotional, and social problems 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.
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)
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.
Number of Infants Referred for Neurological Evaluation to Determine Diagnosis of Cerebral Palsy
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.
Number of Infants With the Indicators of Neurodevelopmental Impairment
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.

Secondary Outcome Measures

Full Information

First Posted
November 13, 2014
Last Updated
June 26, 2020
Sponsor
GlaxoSmithKline
Collaborators
PPD
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1. Study Identification

Unique Protocol Identification Number
NCT02292784
Brief Title
Follow up Study to Assess Long Term Safety and Outcomes in Infants and Children Born to Mothers Participating in Retosiban Treatment Studies
Acronym
ARIOS
Official Title
Follow-Up Study to Assess Long-Term Safety and Outcomes in Infants and Children Born to Mothers Participating in Retosiban Treatment Studies
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
June 1, 2015 (Actual)
Primary Completion Date
September 2, 2019 (Actual)
Study Completion Date
September 2, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
Collaborators
PPD

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective of this study is to assess the safety and outcomes of infants and children who were exposed to retosiban or comparator in utero in the Phase III spontaneous preterm labor (SPTL) treatment studies, to provide assurance that treatment is not associated with significant adverse outcomes in early childhood. The enrolled infants and children will be followed at pre-specified intervals until they reach 24 months chronological age. This study does not require medical interventions or study visits to an investigational site, instead, parents or legal guardians will be prompted at certain time points to complete developmental questionnaires and other data on their children's health status via an electronic device. Data collected during the infant and child follow up study will be managed by a centralized research coordinating center (RCC). Regionally based pediatricians will serve as study principal investigators (referred to as RCC-PIs) for this study. All communications the RCC-PI has with the parent/legal guardian or the child's health care provider (HCP) will occur remotely; there will be no clinic visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstetric Labour, Premature
Keywords
infants, retosiban, Preterm Labor, long-term safety follow-up

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
98 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo (200719 study)
Arm Type
Placebo Comparator
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 will not require any medical interventions or study visits to an investigational site.
Arm Title
Retosiban (200719 and 200721 study)
Arm Type
Experimental
Arm Description
All infants and children born to women who received retosiban (6 milligram [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 will not require any medical interventions or study visits to an investigational site.
Arm Title
Atosiban (200721 study)
Arm Type
Active Comparator
Arm Description
All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 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 will not require any medical interventions or study visits to an investigational site.
Intervention Type
Drug
Intervention Name(s)
Retosiban
Intervention Description
This is a safety follow-up study of infants and children exposed to retosiban during their mother's participation in a Phase III treatment study for SPTL. Infants enrolled in this study will not be administered any investigational product.
Intervention Type
Drug
Intervention Name(s)
Atosiban
Intervention Description
This is a safety follow-up study of infants and children exposed to atosiban comparator during their mother's participation in a Phase III treatment study for SPTL. Infants enrolled in this study will not be administered any investigational product.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
This is a safety follow-up study of infants and children exposed to matching placebo for retosiban/ atosiban during their mother's participation in a Phase III treatment study for SPTL. Infants enrolled in this study will not be administered any investigational product
Primary Outcome Measure Information:
Title
Number of Infants and Children With Newly Diagnosed Chronic Medical Conditions (After 28 Days Post Estimated Date of Delivery)
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. Number of infants and children with newly diagnosed chronic medical conditions are presented.
Time Frame
From 28 days post estimated date of delivery up to 24 months
Title
Number of Infants and Children With Newly Diagnosed Congenital Anomalies (After 28 Days Post Estimated Date of Delivery)
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.
Time Frame
From 28 days post estimated date of delivery up to 24 months
Title
Number of Infant and Child Death (After 28 Days Post Estimated Date of Delivery)
Description
Number of infant and child death that occurred after 28 days post estimated date of delivery and up to 24 months are presented.
Time Frame
From 28 days post estimated date of delivery up to 24 months
Title
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Any Domain at 9 Months
Description
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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.
Time Frame
At 9 months
Title
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Any Domain at 18 Months
Description
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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.
Time Frame
At 18 months
Title
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Any Domain at 24 Months
Description
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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.
Time Frame
At 24 months
Title
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Gross Motor Skills
Description
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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, the pre-defined cut-off score for gross motor skills was 37.38. At 24 months, the pre-defined cut-off score for gross motor skills 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 for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for gross motor skills in the black zone at 9, 18 and 24 months is presented.
Time Frame
9, 18 and 24 months
Title
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Fine Motor Skills
Description
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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, the pre-defined cut-off score for fine motor skills was 34.32. At 24 months, the pre-defined cut-off score for fine motor skills 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 for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for fine motor skills in the black zone at 9, 18 and 24 months is presented.
Time Frame
9, 18 and 24 months
Title
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Communication Skills
Description
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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, the pre-defined cut-off score for communication skills was 13.06. At 24 months, the pre-defined cut-off score for communication skills 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 for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for communication skills in the black zone at 9, 18 and 24 months is presented.
Time Frame
9, 18 and 24 months
Title
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Problem Solving Skills
Description
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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, the pre-defined cut-off score for problem solving skills was 25.74. At 24 months, the pre-defined cut-off score for problem solving skills 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 for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for problem solving skills in the black zone at 9, 18 and 24 months is presented.
Time Frame
9, 18 and 24 months
Title
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Personal Social Skills
Description
The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: 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, the pre-defined cut-off score for personal social skills was 27.19. At 24 months, the pre-defined cut-off score for personal social skills 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 for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for personal social skills in the black zone at 9, 18 and 24 months is presented.
Time Frame
9, 18 and 24 months
Title
Number of Infants Referred for Developmental Evaluation Using Bayley Scales of Infant Development, Third Edition (BSID-III)
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 referred to a developmental specialist for a neurodevelopmental evaluation 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.
Time Frame
9, 18 and 24 months
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)
Description
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 SDs below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation 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.
Time Frame
9, 18 and 24 months
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)
Description
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 SDs below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation 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.
Time Frame
9, 18 and 24 months
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)
Description
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 SDs below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation 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.
Time Frame
9, 18 and 24 months
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)
Description
Any infant who scored below the cut-off i.e., a score greater than or equal to 2 SDs below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation 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.
Time Frame
9, 18 and 24 months
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
Description
The CBCL/1.5 to 5 questionnaire is a parent-completed questionnaire used for assessing behavioral problems and social competencies. It included approximately 100 items that described specific kinds of behavioral, emotional, and social problems 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.
Time Frame
At 24 months
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)
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.
Time Frame
18 and 24 months
Title
Number of Infants Referred for Neurological Evaluation to Determine Diagnosis of Cerebral Palsy
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.
Time Frame
At 24 months
Title
Number of Infants With the Indicators of Neurodevelopmental Impairment
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.
Time Frame
Up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Weeks
Maximum Age & Unit of Time
20 Weeks
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Mother is randomly assigned and dosed (retosiban or comparator) in 1 of the Phase III SPTL retosiban clinical studies. Infant is alive at 28 days post EDD. Written informed consent is obtained from the parent(s) or legal guardian(s) of the infant. The parent/legal guardian of subjects aged 12 to 17 years must also provide written agreement for the infant to participate in the study where required by applicable regulatory and country or state requirements. Exclusion Criteria: There are no formal exclusion criteria for participation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068
Country
United States
Facility Name
GSK Investigational Site
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555-0587
Country
United States
Facility Name
GSK Investigational Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
GSK Investigational Site
City
Freiburg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
GSK Investigational Site
City
Jena
ZIP/Postal Code
07745
Country
Germany
Facility Name
GSK Investigational Site
City
Hadera
ZIP/Postal Code
38100
Country
Israel
Facility Name
GSK Investigational Site
City
Haifa
ZIP/Postal Code
31048
Country
Israel
Facility Name
GSK Investigational Site
City
Holon
ZIP/Postal Code
58100
Country
Israel
Facility Name
GSK Investigational Site
City
Kfar Saba
ZIP/Postal Code
44281
Country
Israel
Facility Name
GSK Investigational Site
City
Petach Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
GSK Investigational Site
City
Safed
ZIP/Postal Code
13100
Country
Israel
Facility Name
GSK Investigational Site
City
Tel-Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
GSK Investigational Site
City
Siena
State/Province
Toscana
ZIP/Postal Code
53100
Country
Italy
Facility Name
GSK Investigational Site
City
Monza
ZIP/Postal Code
20052
Country
Italy
Facility Name
GSK Investigational Site
City
Miyagi
ZIP/Postal Code
989-3126
Country
Japan
Facility Name
GSK Investigational Site
City
Miyazaki
ZIP/Postal Code
889-1692
Country
Japan
Facility Name
GSK Investigational Site
City
Seongnam
ZIP/Postal Code
463-712
Country
Korea, Republic of
Facility Name
GSK Investigational Site
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
GSK Investigational Site
City
Seoul
ZIP/Postal Code
135-081
Country
Korea, Republic of
Facility Name
GSK Investigational Site
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44340
Country
Mexico
Facility Name
GSK Investigational Site
City
Monterrey
State/Province
Nuevo León
ZIP/Postal Code
64460
Country
Mexico
Facility Name
GSK Investigational Site
City
Ciudad Obregon
State/Province
Sonora
ZIP/Postal Code
85000
Country
Mexico
Facility Name
GSK Investigational Site
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Facility Name
GSK Investigational Site
City
Uppsala
ZIP/Postal Code
SE-751 85
Country
Sweden
Facility Name
GSK Investigational Site
City
Sunderland
State/Province
Tyne & Wear
ZIP/Postal Code
SR4 7TP
Country
United Kingdom
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing URL
http://clinicalstudydatarequest.com

Learn more about this trial

Follow up Study to Assess Long Term Safety and Outcomes in Infants and Children Born to Mothers Participating in Retosiban Treatment Studies

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