NEWBORN-1: A Phase III Efficacy and Safety Study of Intravenous Retosiban Versus Placebo for Women in Spontaneous Preterm Labor

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02377466
• Collaborator: PPD (Industry)
• Enrollment: 25
• Locations: 50
• Arms: 2
• Actual Duration (Months): 16.8
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The study's primary objective is to demonstrate the superiority of retosiban to prolong pregnancy and improve neonatal outcomes compared with placebo. It is a Phase III, randomized, double-blind, parallel-group, multicenter study and will be conducted in approximately 900 females, aged 12 to 45 years, with an uncomplicated, singleton pregnancy and intact membranes in preterm labor between 24^{0/7 and 33}6/7 weeks of gestation. Eligible maternal subjects will be randomly assigned in a 1:1 ratio to receive either retosiban IV infusion or placebo IV infusion over 48 hours. If not previously administered, antenatal corticosteroid treatment should be administered as either (1) two 12-mg doses of betamethasone given intramuscularly 24 hours apart or (2) four 6-mg doses of betamethasone administered intramuscularly every 12 hours. A single rescue course of antenatal corticosteroids is permitted if the antecedent treatment was at least 7 days prior to study enrolment. Investigators have discretion to use a standardized regimen of magnesium sulphate, as well as intrapartum antibiotic prophylaxis for perinatal group B streptococcal infection. Prior to randomization, each subject will be stratified by progesterone treatment and gestational age. The progesterone strata will consist of subjects on established progesterone therapy or subjects not on established progesterone therapy at Screening. The study will comprise 6 phases: Screening, Inpatient Randomized Treatment, Post Infusion Assessment, Delivery, Maternal Post-Delivery Assessment, and Neonatal Medical Review. The duration of any subject's (maternal or neonatal) participation in the study will be variable and dependent on gestational ages (GA) at study entry and the date of delivery.

Condition or Disease	Intervention/Treatment	Phase
Obstetric Labour, Premature	Drug: Retosiban IV infusion; Drug: Placebo IV infusion	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-blind, Multicenter, Phase III Study Comparing the Efficacy and Safety of Retosiban Versus Placebo for Women in Spontaneous Preterm Labor
• Actual Study Start Date: Feb 29, 2016
• Actual Primary Completion Date: Jul 24, 2017
• Actual Study Completion Date: Jul 24, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Retosiban Retosiban treatment will be administered as a 6 mg IV loading dose over 5 minutes followed by a 6 milligram per hour (mg/hour) continuous infusion over 48 hours. For subjects with an inadequate response after the first hour of treatment, another 6 mg loading dose will be administered and infusion rate will be increased to 12 mg/hour for the remainder of the 48 hour treatment period. The retosiban dosing regimen will require adjustment in subjects treated concomitantly with drugs that are strong Cytochrome 3A4 inhibitors or inducers.	Drug: Retosiban IV infusion; Retosiban for IV administration will be supplied as solution for infusion, consisting of a clear colorless solution of retosiban at a concentration of 15 milligram per milliliter (mg/mL).
Placebo Comparator: Placebo The placebo control will be a normal saline (0.9% sodium chloride [NaCl]) infusion matched for the loading dose and continuous infusion rates, including a dose increase in subjects with an inadequate response after the first hour of treatment.	Drug: Placebo IV infusion; 0.9% NaCl matched for the retosiban loading dose and continuous infusion rates

Outcome Measures

Primary Outcome Measures

1. Time to Delivery or Treatment Failure, Whichever Occurs First [Up to 17 weeks]

   Time to delivery or treatment failure is the number of days from the first dose of study treatment until delivery or treatment failure whichever occurs first. Treatment failure is defined as the administration of any putative tocolytic medication for treatment of preterm labor or as prophylaxis of preterm labor. Maternal intent-to-treat (ITT) Population comprised of all mothers randomly assigned to treatment who have been exposed to study treatment irrespective of their compliance to the planned course of treatment. The mean number of days to delivery or treatment failure along with standard deviation has been presented. Statistical analysis was not performed due to early termination of the study and resultant small sample size.

2. Number of Neonates With Any Diagnosis From the Neonatal Morbidity and Mortality Composite Component [Up to 28 days after the estimated date of delivery (EDD) of 40 0/7 weeks]

   The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, respiratory distress syndrome (RDS), bronchopulmonary dysplasia, necrotizing enterocolitis or isolated perforation, sepsis based on positive blood culture with clinical features of sepsis, meningitis based on positive results for cerebrospinal fluid culture performed as part of infection workup, retinopathy of prematurity, intraventricular hemorrhage (IVH), white matter injury and cerebellar hemorrhage. Neonates with any of the composite component has been presented. Statistical analysis was not performed due to early termination of study and resultant small sample size. Neonatal ITT Population comprised of all neonates whose mothers were the randomized participants who have been exposed to study treatment, that is, mothers from the ITT Population.

Secondary Outcome Measures

1. Time to Delivery [Up to 17 weeks]

   The time to delivery was calculated as the days between the delivery and start time of the study treatment infusion using the formula: Time to delivery (days) = (date and time of delivery minus date and time of start of infusion) divided by (24 multiplied by 60). The mean number of days to delivery along with standard deviation has been presented.

2. Number of Participants With Births Prior to 37 0/7 Weeks Gestation [Up to 13 weeks]

   Gestational age at birth (weeks) is defined as the gestational age when the baby is born. Participants were considered to have delivered prior to 37 0/7 weeks, that is preterm, if the gestational age at birth is less than 37 0/7 weeks. The number of participants who delivered prior to 37 0/7 weeks gestation has been presented.

3. Number of Participants With Births at Term [Up to 17 weeks]

   Participants were considered to have delivered at term if the gestational age was >=37 0/7. The number of participants who delivered at term, that is, 37 0/7 to 41 6/7 weeks gestation has been presented.

4. Length of Neonatal Hospital Stay [Up to 28 days post EDD of 40 0/7 weeks gestation]

   The length of stay was collected from medical records and was calculated as the days between the delivery date and time and discharge date and time.

5. Number of Participants With Births Prior to 35 0/7 Weeks Gestation [Up to 11 weeks]

   The number of participants who delivered prior to 35 0/7 weeks gestation has been presented.

6. Number of Participants With Births Prior to 32 0/7 Weeks Gestation [Up to 8 weeks]

   The number of participants who delivered prior to 32 0/7 weeks gestation has been presented. Only those maternal participants who were randomized prior to 32 0/7 week's gestation and delivered were included.

7. Number of Participants With Births Prior to 28 0/7 Weeks Gestation [Up to 4 weeks]

   The number of participants who delivered prior to 28 0/7 weeks gestation has been presented. Only those maternal participants who were randomized prior to 28 0/7 week's gestation and delivered were included.

8. Number of Participants With Births <=7 Days From the First Study Treatment [Up to 7 days]

   The number of participants who delivered in less than or equal to 7 days from first dose of study treatment has been presented.

9. Number of Participants With Births at <=48 Hours From the First Study Treatment [Up to 48 hours]

   The number of participants who delivered in less than or equal to 48 hours from first dose of study treatment has been presented.

10. Number of Participants With Births at <=24 Hours From the First Study Treatment [Up to 24 hours]

    The number of participants who delivered in less than or equal to 24 hours from first dose of study treatment has been presented.

11. Number of Neonates With Any of the Co-primary Composite Neonatal Morbidity and Mortality, Excluding RDS [Up to 28 weeks after EDD (40 weeks gestation)]

    The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, RDS, bronchopulmonary dysplasia, necrotizing enterocolitis or isolated perforation, sepsis based on positive blood culture with clinical features of sepsis, meningitis based on positive results for cerebrospinal fluid culture performed as part of infection workup, retinopathy of prematurity, IVH, white matter injury and cerebellar hemorrhage. The number of neonates with any co-primary composite neonatal morbidity and mortality component, excluding RDS has been presented.

12. Number of Neonates With Each Individual Component of the Composite Neonatal Morbidity and Mortality [Up to 28 days after the EDD of 40 0/7 weeks]

    The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, RDS, bronchopulmonary dysplasia, necrotizing enterocolitis or isolated perforation, sepsis based on positive blood culture with clinical features of sepsis, meningitis based on positive results for cerebrospinal fluid culture performed as part of infection workup, retinopathy of prematurity, IVH, white matter injury and cerebellar hemorrhage. The number of neonates with each individual component of the composite component has been presented.

13. Number of Neonatal Participants With Admission to a Particular Hospital Unit [Up to 28 days post EDD (40 0/7 weeks gestation)]

    Neonatal healthcare resource utilization was collected from review of medical records. The number of neonatal participants who were admitted to a particular hospital unit that is, level III (or higher) intensive neonatal care (NICU), Intensive care unit (ICU), general ward, Level I - Basic Neonatal care, Well born nursery (SCBU) and Level II-Special Care Newborn nursery high dependency (NHDU) has been summarized. Neonatal Safety Population consisted of neonates whose mothers received study treatment.

14. Length of Stay in Specialized Care Unit [Up to 28 days post EDD (40 0/7 weeks gestation)]

    Neonatal healthcare resource utilization was collected from review of medical records. The length of stay in a specialized care unit (NICU or ICU) has been presented for neonatal participants with admission to ICU or NICU.

15. Number of Newborn Participants With Hospital Readmission [Up to 28 days of EDD (40 0/7 weeks gestation)]

    Newborn hospital readmission following hospitalization for birth was collected from the newborn's medical records. The number of newborn participants who had readmission to hospital is presented.

16. Length of Stay Following Readmission to Hospital [Up to 28 days after EDD (40 0/7 weeks gestation)]

    Newborn hospital readmission following hospitalization for birth was collected from the newborn's medical records. Length of stay in hospital following readmission is presented for neonates.

17. Number of Participants With Ambulatory Surgery [Up to 28 days post EDD (40 0/7 weeks gestation)]

    Information regarding participants who had ambulatory surgery was collected from the newborn medical records. The number of neonatal participants with ambulatory surgery is presented.

18. Time to Treatment Failure [Up to 17 weeks]

    Treatment failure is defined as the administration of any putative tocolytic medication for treatment of preterm labor or as prophylaxis of preterm labor. Time to treatment failure is the number of days from the first dose of study treatment until treatment failure. The mean number of days to delivery or treatment failure along with standard deviation has been presented. Only those maternal participants with treatment failure were included in the analysis. NA indicates standard deviation could not be calculated as only one participant was analyzed.

19. Number of Participants Who Received Any Putative Tocolytic [Up to 17 weeks]

    A putative tocolytic medication was the medication administered for active preterm labor or as prevention of preterm labor and included calcium channel blockers, nonsteroidal anti-inflammatory drugs, or beta agonists, or magnesium sulfate doses that exceeded prespecified IV loading doses, infusion rates, or total duration of administration.

20. Number of Participants With Subsequent Preterm Labor [Up to 11 weeks]

    The participants who had not delivered after 48 hours post-infusion were contacted to determine if they had delivered or experienced any subsequent episodes of preterm labor. A subsequent episode of preterm labor was only recorded if the participant reported it to the Principal Investigator during one of the telephone follow-up calls but did not then go on to immediately deliver. However, if labor started and led to immediate delivery, then the only data collected would be the pre-specified delivery data and thus would not be counted as a subsequent episode of preterm labor. The number of participants who had a subsequent episode of preterm labor after administration of the study treatment has been presented. Maternal Safety Population comprised of all maternal participants randomly assigned to treatment who have been exposed to study treatment.

21. Number of Maternal Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to 6 weeks after delivery]

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that mey require medical or surgical intervention to prevent one of the other outcomes described before; is associated with liver injury and impaired liver function. Maternal Safety Population comprised of all mothers randomly assigned to treatment who have been exposed to study treatment. The number of maternal participants who experienced at least one AE and one SAE has been presented.

22. Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) [Baseline and up to 9 days]

    SBP and DBP were measured with participants in a semirecumbent or seated position. SBP and DBP were measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

23. Change From Baseline in Heart Rate [Baseline and up to 9 days]

    Heart rate was measured with the participants in a semirecumbent or seated position. Heart rate was measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

24. Change From Baseline in Temperature [Baseline and up to 1 week]

    Temperature was measured with the participants in a semirecumbent or seated position. Temperature was measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

25. Change From Baseline in Respiratory Rate [Baseline and up to 1 week]

    Respiratory rate was measured with the participants in a semirecumbent or seated position. Respiratory rate was measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

26. Change From Baseline in Hematocrit Levels [Baseline and up to 1 week]

    Blood samples were collected for the evaluation of change in hematocrit levels from Baseline. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

27. Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) [Baseline and up to 1 week]

    Blood samples were collected for the evaluation of change in hemoglobin levels and MCHC from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

28. Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count [Baseline and up to 1 week]

    Blood samples were collected for the evaluation of change in basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes count. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

29. Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) [Baseline and up to 1 week]

    Blood samples were collected for the evaluation of change in MCV and MPV from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

30. Change From Baseline in Erythrocyte Level [Baseline and up to 1 week]

    Blood samples were collected for the evaluation of change in erythrocyte level from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

31. Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Levels [Baseline and up to 1 week]

    Blood samples were collected for the evaluation of change in ALP, ALT, AST, GGT and LDH from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

32. Change From Baseline in Albumin and Protein Levels [Baseline and up to 1 week]

    Blood samples were collected for the evaluation of change in albumin and protein levels from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

33. Change From Baseline in Anion Gap, Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level [Baseline and up to 1 week]

    Blood samples were collected for the evaluation of change from Baseline in levels of anion gap, calcium, chloride, carbon dioxide, glucose, potassium, magnesium, phosphate, and sodium. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

34. Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels [Baseline and up to 1 week]

    Blood samples were collected for the evaluation of change from Baseline in levels of direct bilirubin, bilirubin, indirect bilirubin, creatinine and urate. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

35. Number of Participants Who Discontinued Study Treatment Due to Clinical and Laboratory Toxicities [Up to 48 hours post-infusion]

    Number of maternal participants who discontinued study treatment due to clinical and laboratory toxicities is presented.

36. Number of Maternal Participants With a Score of 12 or Higher on the Edinburgh Postnatal Depression Scale (EPDS) [Up to 6 weeks post delivery]

    The effect of preterm birth on maternal health status was assessed using the EPDS. The EPDS is a 10-item self-reported assessment of depression, validated for administration during both the antenatal and the post-natal periods. Items are rated on a 4-point variable Likert scale, ranging from 0 to 3. The total score was calculated by adding individual scores for each item and ranged from 0 to 30. A score of less than 8 indicates depression not likely; score of 9 to 11 indicates possible depression and a score of more than 12 indicates an increased probability of depression. Maternal participants were required to complete the EPDS at the maternal follow-up assessment 6 weeks post-delivery.

37. Number of Maternal Participants With AEs of Special Interest (AESI). [Up to 6 weeks post-delivery]

    Maternal AESI included: maternal death; chorioamnionitis and its complications (clinical chorioamnionitis, preterm premature rupture of membranes, endomyometritis, wound infection, pelvic abscess, bacteremia, septic shock, disseminated intravascular coagulation, and adult RDS); placental abruption; postpartum hemorrhage - postpartum hemorrhage and/or retained placenta and pulmonary edema. The number of participants with at least one AESI has been presented.

38. Number of Maternal Participants With Disease Related AEs (DRE) [Up to 6 weeks post-delivery]

    Maternal DREs included: signs and symptoms of labor discomfort (example, cramping, backache, muscle aches, nausea); subsequent episodes of preterm labor and hospitalization for delivery. The number of participants with at least one DRE has been presented.

39. Number of Fetal Participants With AEs and SAEs Prior to Delivery [Up to 17 weeks post-infusion]

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the other outcomes described before; is associated with liver injury and impaired liver function. Fetal AEs and SAEs included the adverse events that were experienced by the fetus prior to delivery. The number of fetal participants who experienced at least one AE and one SAE has been presented.

40. Number of Participants With Fetal Acidosis [Up to 16 weeks]

    The number of participants with fetal acidosis is presented.

41. Number of Participants With Fetal AESI [Up to 17 weeks]

    Fetal AESI included: intrauterine fetal demise; category II or III fetal heart rate tracing; and fetal inflammatory response syndrome characterized by cord blood interleukin-6 >11 picogram per milliliter (pg/mL), funisitis, or chorionic vasculitis. The number of participants who experienced at least one AESI has been presented.

42. Neonatal APGAR Scores [Up to 5 minutes after birth]

    APGAR is a quick test to assess the health of new born children. The test is performed at 1 and 5 minutes after birth. APGAR scale is determined by evaluating the new born on five categories (appearance, pulse, grimace, activity and respiration) on a scale from zero to two, then summing up the five values obtained. APGAR score ranges from 0 to 10 where a score of 7 and above is normal. The mean and standard deviation of APGAR scores at one minute and at five minutes of birth has been presented.

43. Weight of Neonates [Up to 17 weeks]

    The weight of neonates was obtained from the neonate birth record. The mean weight of neonates and standard deviation has been presented.

44. Head Circumference of Neonates [Up to 17 weeks]

    The head circumference was determined from the neonate birth record.

45. Number of Neonatal Participants With AEs and SAEs [Up to 28 days after the EDD of 40 weeks gestation]

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the other outcomes described before; is associated with liver injury and impaired liver function. The number of participants who experienced at least one AE and one SAE has been presented. Neonatal Safety Population consisted of neonates whose mothers received randomized treatment.

46. Number of Neonatal Participants With AESI [Up to 28 days after EDD of 40 weeks gestation]

    Neonatal AESI included: Neonatal death; Asphyxia; Infections (early onset neonatal sepsis, septic shock, pneumonia, meningitis); RDS; Hypotension; IVH/periventricular leukomalacia; Bronchopulmonary dysplasia; Neonatal acidosis; Hyperbilirubinemia; Necrotizing enterocolitis; and Hypoxic ischemic encephalopathy. The number of neonatal participants who experienced at least one AESI has been presented.

47. Number of Neonatal Participants With DRE [Up to 28 days after EDD of 40 weeks gestation]

    The disease related neonatal events occurring in Infants born prior to 37 completed weeks included: apnea (severe), respiratory failure due to fatigue, hypoxia, or air leak from alveolar injury, patent ductus arteriosus, bradycardia, ventriculomegaly, cerebellar hemorrhage, hydrocephalus other than congenital, gastroesophageal reflux, aspiration pneumonia, anemia, retinopathy of prematurity (all stages), hearing disorder, temperature instability and hypoglycemia. The number of participants with at least one DRE has been presented.

48. Maternal Length of Stay in Hospital [Up to 28 days post EDD (40 0/7 weeks gestation)]

    Details on maternal health care resource use (both for hospitalizations related to preterm labor not resulting in a delivery and hospitalizations related to preterm labor/normal labor resulting in a delivery) associated with an episode of preterm labor, preterm delivery and normal term delivery (>= 37 weeks gestation) were collected from review of medical records. Length of hospital stay associated with hospital admission for preterm labor and normal term labor/term delivery is presented. One participant in the retosiban arm did not have hospitalization data; hence, was excluded from the analysis at delivery. Only participants with data available at the specified time points were analyzed (indicated by n=X) in category titles. NA indicates standard deviation could not be calculated as only one participant was analyzed.

49. Number of Participants With Hospital Admissions Related to Preterm Labor and Preterm Delivery [Up to 28 days after EDD (40 0/7 weeks of gestation)]

    Maternal healthcare resource utilization associated with an episode of preterm labor and preterm delivery were collected from the review of medical records. One participant in the retosiban arm did not have hospitalization data; hence, was excluded from the analysis at delivery. The number of participants who had hospital admission for preterm labor and preterm delivery has been presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

50. Number of Participants Admitted to Particular Hospital Unit [Up to 28 days post EDD (40 0/7 weeks gestation)]

    Maternal healthcare resource utilization associated with an episode of preterm labor, preterm delivery and normal term delivery were collected from the review of medical records. The number of participants who were admitted to a particular hospital unit has been presented.

51. Number of Participants With Different Modes of Transportation to Hospital [Up to 28 days post EDD (40 0/7 weeks gestation)]

    The means by which the maternal participants were transported to the hospital i.e. ground ambulance/emergency vehicle (gr. amb/emer. veh), air ambulance, family member or other means were obtained from the review of medical records. The number of maternal participants with the corresponding mode of transportation is presented for preterm labor visit and delivery visit. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).

52. Retosiban Clearance [Day 1 (2 to 4 hours, 10 to 14 hours) and Day 2 (22 to 26 hours, and 48 to 54 hours) post-infusion]

    Maternal blood samples were collected at the indicated time points for pharmacokinetic analysis. Data is a combined data set. Data is presented for 10 participants from retosiban arm of study 200719 (NCT02377466) and 43 participants from retosiban arm of study 200721 (NCT02292771).

53. Volume of Distribution of Retosiban [Day 1 (2 to 4 hours, 10 to 14 hours) and Day 2 (22 to 26 hours, and 48 to 54 hours) post-infusion]

    Maternal blood samples were collected at the indicated time points for pharmacokinetic analysis. Data is a combined data set. Data is presented for 10 participants from retosiban arm of study 200719 (NCT02377466) and 43 participants from retosiban arm of study 200721 (NCT02292771).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed and dated written informed consent is required prior to a subject's participation in the study and the performance of any protocol specific procedures. Adolescents aged 12 to 17 years must provide written agreement to participate in the study in accordance with applicable regulatory and country or state requirements. Subjects will also be asked to sign a release for medical records at the time of consenting to allow access to both the maternal and neonatal records including information about delivery and infant care as well as information collected prior to the consent having been signed.

• Females aged 12 to 45 years, with an uncomplicated, singleton pregnancy and intact membranes in preterm.

• Gestational age between 24 and 33 weeks as determined by (1) known fertilization date, either in vitro fertilization or intrauterine insemination, (2) last menstrual period confirmed by the earliest ultrasound prior to 24 weeks gestation, or (3) the earliest ultrasound alone prior to 24 weeks gestation, whichever is the most accurate method available for each subject. In situations where prenatal ultrasound records are not available at the time the subject presents, the investigator will make every effort to obtain these records (either via computer records, directly from the subject's primary care obstetrician, or via telephone). However, in cases in which these records are not readily available (e.g., off hours, holiday), it is within the investigator's discretion to use GA based on a verbal history from the subject with the intent of getting confirmation from the medical records as soon as possible.

• Females must be diagnosed with preterm labor according to both of the following criteria: a) Regular uterine contractions at a rate of >=4 contractions of at least 30 seconds' duration during a 30-minute interval confirmed by tocodynamometry and at least 1 of the following, b) Cervical dilation >=2 centimeter (cm) and <=4 cm by digital cervical examination or c) If <2 cm dilation by digital cervical examination, a cervical change consisting of an increase of at least 25% effacement or 1-cm dilation.

• Current or past tocolytic treatment as follows: a) Subjects in whom tocolytic treatment has not been initiated prior to consent are eligible for the study, b) Transferred or referred subjects for whom parenteral magnesium sulfate treatment has been started before Screening are eligible provided they meet all eligibility criteria, c) Subjects receiving a prohibited tocolytic in this study are eligible only if the treatment is stopped before randomization and provided they meet all eligibility criteria, d) Subjects with a historical failure of a tocolytic treatment in a previous episode of preterm labor during the current pregnancy are eligible provided they meet all eligibility criteria.

Exclusion Criteria:

• Fever with a temperature >100.4 degree Fahrenheit (38 degree centigrade) for more than 1 hour or >=101 degree Fahrenheit (38.3 degree centigrade) in the 24 hours prior to the start of study treatment.

• Women with maternal-fetal conditions that potentially necessitate the need for delivery, such as pre-eclampsia or fetal compromise.

• A fetus with any diagnosis, condition, treatment, or other factor that in the opinion of the investigator has the potential to affect or confound assessments of efficacy or safety (for example: nonreassuring fetal status, intrauterine growth restriction, major congenital anomaly).

• Preterm premature rupture of membranes.

• Women with any confirmed or suspected contraindication to prolongation of pregnancy, such as placental abruption, chorioamnionitis, or placenta previa.

• Evidence of polyhydramnios (AFI >25 cm) or oligohydramnios (AFI <5 cm).

• Women with co-morbid medical or obstetric conditions that in the opinion of the investigator have the potential to complicate the pregnancy course and outcomes, such as uncontrolled hypertension or uncontrolled diabetes (if known, history of glycosylated hemoglobin >8% at any time during pregnancy), or compromise the safety of the subject, such as underlying cardiovascular disorder (specifically ischemic cardiac disease, congenital heart disease, pulmonary hypertension, valvular heart disease, arrhythmias, and cardiomyopathy).

• Women with a history of substance abuse during the pregnancy or urine drug screen positive for cocaine, phencyclidine (PCP), methamphetamine, or amphetamine.

• Women in whom the combination of history and screening test results is suggestive of abuse or dependency that may have the potential to complicate the pregnancy outcome.

• Women with any diagnosis, condition, treatment, or other factor that, in the opinion of the investigator, has the potential to affect or confound assessments of efficacy or safety.

• Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).

• History of sensitivity to any of the investigational products (IPs) or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline/ Pharmaceutical Product Development (GSK/PPD) medical monitor, contraindicates the subject's participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35233
2	GSK Investigational Site	Mobile	Alabama	United States	36604
3	GSK Investigational Site	Tucson	Arizona	United States	85712
4	GSK Investigational Site	Colton	California	United States	92324
5	GSK Investigational Site	Orange	California	United States	92868
6	GSK Investigational Site	Washington	District of Columbia	United States	20010
7	GSK Investigational Site	Jacksonville	Florida	United States	32209
8	GSK Investigational Site	Augusta	Georgia	United States	30912
9	GSK Investigational Site	Columbus	Georgia	United States	31904
10	GSK Investigational Site	Chicago	Illinois	United States	60611
11	GSK Investigational Site	Chicago	Illinois	United States	60637
12	GSK Investigational Site	Maywood	Illinois	United States	60153
13	GSK Investigational Site	Park Ridge	Illinois	United States	60068
14	GSK Investigational Site	Kansas City	Kansas	United States	66160
15	GSK Investigational Site	Louisville	Kentucky	United States	40202
16	GSK Investigational Site	New Orleans	Louisiana	United States	70115
17	GSK Investigational Site	Jackson	Mississippi	United States	39216-4505
18	GSK Investigational Site	Richmond Heights	Missouri	United States	63117
19	GSK Investigational Site	Neptune	New Jersey	United States	07753
20	GSK Investigational Site	Newark	New Jersey	United States	07103
21	GSK Investigational Site	Bronx	New York	United States	10461
22	GSK Investigational Site	Brooklyn	New York	United States	11201
23	GSK Investigational Site	New York	New York	United States	10032
24	GSK Investigational Site	Durham	North Carolina	United States	27710
25	GSK Investigational Site	Cleveland	Ohio	United States	44106
26	GSK Investigational Site	Dayton	Ohio	United States	45409
27	GSK Investigational Site	Portland	Oregon	United States	97239
28	GSK Investigational Site	Lancaster	Pennsylvania	United States	17601
29	GSK Investigational Site	Charleston	South Carolina	United States	29425
30	GSK Investigational Site	Chattanooga	Tennessee	United States	37403
31	GSK Investigational Site	Galveston	Texas	United States	77555-0587
32	GSK Investigational Site	Charlottesville	Virginia	United States	22908
33	GSK Investigational Site	Tacoma	Washington	United States	98431
34	GSK Investigational Site	London	Ontario	Canada	N6A 4G5
35	GSK Investigational Site	Roma	Lazio	Italy	00168
36	GSK Investigational Site	Milano	Lombardia	Italy	20132
37	GSK Investigational Site	Hokkaido		Japan	060-8543
38	GSK Investigational Site	Hyogo		Japan	650-0047
39	GSK Investigational Site	Kagoshima		Japan	890-8760
40	GSK Investigational Site	Miyagi		Japan	989-3126
41	GSK Investigational Site	Miyazaki		Japan	889-1692
42	GSK Investigational Site	Nagasaki		Japan	856-8562
43	GSK Investigational Site	Okinawa		Japan	904-2293
44	GSK Investigational Site	Saitama		Japan	350-0495
45	GSK Investigational Site	Tochigi		Japan	321-0293
46	GSK Investigational Site	Tokyo		Japan	135-8577
47	GSK Investigational Site	Tokyo		Japan	142-8666
48	GSK Investigational Site	Tokyo		Japan	157-8535
49	GSK Investigational Site	Tokyo		Japan	206-8512
50	GSK Investigational Site	London		United Kingdom	SE1 7EH

Sponsors and Collaborators

• GlaxoSmithKline
• PPD

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Statistical Analysis Plan - Sep 8, 2017
• Study Protocol - Jan 5, 2017

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02377466
• Other Study ID Numbers: 200719; 2014-003326-41
• First Posted: Mar 3, 2015
• Last Update Posted: Jul 28, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Spontaneous Preterm Labor; GSK221149; Retosiban
• Additional relevant MeSH terms: Obstetric Labor, Premature

Study Results

Participant Flow

Recruitment Details	NEWBORN-1 was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study to investigate efficacy and safety of retosiban in female participants aged 12 to 45 years with an uncomplicated singleton pregnancy in preterm labor with intact membranes between 24 0/7 and 33 6/7 weeks gestation. The study was conducted in 3 countries.
Pre-assignment Detail	Twenty-five participants were randomly assigned to study treatments: 12 participants to retosiban intravenous (IV) infusion and 13 participants to matched placebo IV infusion. Two participants randomized to retosiban arm did not receive study treatment. The study was terminated early due to feasibility of recruiting the study in a timely manner.

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Period Title: Overall Study
STARTED	13	12
Treated	13	10
COMPLETED	13	10
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Placebo	Retosiban	Total
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.	Total of all reporting groups
Overall Participants	13	10	23
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	26.5 (6.78)	27.7 (6.73)	27.0 (6.63)
Sex: Female, Male (Count of Participants)
Female	13 100%	10 100%	23 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
African American/African Heritage	2 15.4%	2 20%	4 17.4%
Asian-Central/South Asian Heritage	0 0%	1 10%	1 4.3%
Asian-East Asian Heritage	1 7.7%	0 0%	1 4.3%
Asian-Japanese Heritage	4 30.8%	2 20%	6 26.1%
Asian-South East Asian Heritage	1 7.7%	0 0%	1 4.3%
White-White/Caucasian/European Heritage	5 38.5%	5 50%	10 43.5%

Outcome Measures

1. Primary Outcome

Title	Time to Delivery or Treatment Failure, Whichever Occurs First
Description	Time to delivery or treatment failure is the number of days from the first dose of study treatment until delivery or treatment failure whichever occurs first. Treatment failure is defined as the administration of any putative tocolytic medication for treatment of preterm labor or as prophylaxis of preterm labor. Maternal intent-to-treat (ITT) Population comprised of all mothers randomly assigned to treatment who have been exposed to study treatment irrespective of their compliance to the planned course of treatment. The mean number of days to delivery or treatment failure along with standard deviation has been presented. Statistical analysis was not performed due to early termination of the study and resultant small sample size.
Time Frame	Up to 17 weeks

Outcome Measure Data

Analysis Population Description

Maternal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Mean (Standard Deviation) [Days]	11.10 (14.987)	18.91 (22.993)

2. Primary Outcome

Title	Number of Neonates With Any Diagnosis From the Neonatal Morbidity and Mortality Composite Component
Description	The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, respiratory distress syndrome (RDS), bronchopulmonary dysplasia, necrotizing enterocolitis or isolated perforation, sepsis based on positive blood culture with clinical features of sepsis, meningitis based on positive results for cerebrospinal fluid culture performed as part of infection workup, retinopathy of prematurity, intraventricular hemorrhage (IVH), white matter injury and cerebellar hemorrhage. Neonates with any of the composite component has been presented. Statistical analysis was not performed due to early termination of study and resultant small sample size. Neonatal ITT Population comprised of all neonates whose mothers were the randomized participants who have been exposed to study treatment, that is, mothers from the ITT Population.
Time Frame	Up to 28 days after the estimated date of delivery (EDD) of 40 0/7 weeks

Outcome Measure Data

Analysis Population Description

Neonatal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	4 30.8%	2 20%

3. Secondary Outcome

Title	Time to Delivery
Description	The time to delivery was calculated as the days between the delivery and start time of the study treatment infusion using the formula: Time to delivery (days) = (date and time of delivery minus date and time of start of infusion) divided by (24 multiplied by 60). The mean number of days to delivery along with standard deviation has been presented.
Time Frame	Up to 17 weeks

Outcome Measure Data

Analysis Population Description

Maternal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Mean (Standard Deviation) [Days]	16.32 (18.595)	19.18 (22.770)

4. Secondary Outcome

Title	Number of Participants With Births Prior to 37 0/7 Weeks Gestation
Description	Gestational age at birth (weeks) is defined as the gestational age when the baby is born. Participants were considered to have delivered prior to 37 0/7 weeks, that is preterm, if the gestational age at birth is less than 37 0/7 weeks. The number of participants who delivered prior to 37 0/7 weeks gestation has been presented.
Time Frame	Up to 13 weeks

Outcome Measure Data

Analysis Population Description

Maternal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	9 69.2%	8 80%

5. Secondary Outcome

Title	Number of Participants With Births at Term
Description	Participants were considered to have delivered at term if the gestational age was >=37 0/7. The number of participants who delivered at term, that is, 37 0/7 to 41 6/7 weeks gestation has been presented.
Time Frame	Up to 17 weeks

Outcome Measure Data

Analysis Population Description

Maternal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	4 30.8%	2 20%

6. Secondary Outcome

Title	Length of Neonatal Hospital Stay
Description	The length of stay was collected from medical records and was calculated as the days between the delivery date and time and discharge date and time.
Time Frame	Up to 28 days post EDD of 40 0/7 weeks gestation

Outcome Measure Data

Analysis Population Description

Neonatal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Mean (Standard Deviation) [Days]	37.50 (34.537)	26.05 (32.689)

7. Secondary Outcome

Title	Number of Participants With Births Prior to 35 0/7 Weeks Gestation
Description	The number of participants who delivered prior to 35 0/7 weeks gestation has been presented.
Time Frame	Up to 11 weeks

Outcome Measure Data

Analysis Population Description

Maternal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	9 69.2%	7 70%

8. Secondary Outcome

Title	Number of Participants With Births Prior to 32 0/7 Weeks Gestation
Description	The number of participants who delivered prior to 32 0/7 weeks gestation has been presented. Only those maternal participants who were randomized prior to 32 0/7 week's gestation and delivered were included.
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description

Maternal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	9	6
Number [Participants]	6 46.2%	2 20%

9. Secondary Outcome

Title	Number of Participants With Births Prior to 28 0/7 Weeks Gestation
Description	The number of participants who delivered prior to 28 0/7 weeks gestation has been presented. Only those maternal participants who were randomized prior to 28 0/7 week's gestation and delivered were included.
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

Maternal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	2	2
Number [Participants]	2 15.4%	1 10%

10. Secondary Outcome

Title	Number of Participants With Births <=7 Days From the First Study Treatment
Description	The number of participants who delivered in less than or equal to 7 days from first dose of study treatment has been presented.
Time Frame	Up to 7 days

Outcome Measure Data

Analysis Population Description

Maternal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	5 38.5%	5 50%

11. Secondary Outcome

Title	Number of Participants With Births at <=48 Hours From the First Study Treatment
Description	The number of participants who delivered in less than or equal to 48 hours from first dose of study treatment has been presented.
Time Frame	Up to 48 hours

Outcome Measure Data

Analysis Population Description

Maternal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	3 23.1%	3 30%

12. Secondary Outcome

Title	Number of Participants With Births at <=24 Hours From the First Study Treatment
Description	The number of participants who delivered in less than or equal to 24 hours from first dose of study treatment has been presented.
Time Frame	Up to 24 hours

Outcome Measure Data

Analysis Population Description

Maternal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	3 23.1%	1 10%

13. Secondary Outcome

Title	Number of Neonates With Any of the Co-primary Composite Neonatal Morbidity and Mortality, Excluding RDS
Description	The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, RDS, bronchopulmonary dysplasia, necrotizing enterocolitis or isolated perforation, sepsis based on positive blood culture with clinical features of sepsis, meningitis based on positive results for cerebrospinal fluid culture performed as part of infection workup, retinopathy of prematurity, IVH, white matter injury and cerebellar hemorrhage. The number of neonates with any co-primary composite neonatal morbidity and mortality component, excluding RDS has been presented.
Time Frame	Up to 28 weeks after EDD (40 weeks gestation)

Outcome Measure Data

Analysis Population Description

Neonatal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	3 23.1%	0 0%

14. Secondary Outcome

Title	Number of Neonates With Each Individual Component of the Composite Neonatal Morbidity and Mortality
Description	The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, RDS, bronchopulmonary dysplasia, necrotizing enterocolitis or isolated perforation, sepsis based on positive blood culture with clinical features of sepsis, meningitis based on positive results for cerebrospinal fluid culture performed as part of infection workup, retinopathy of prematurity, IVH, white matter injury and cerebellar hemorrhage. The number of neonates with each individual component of the composite component has been presented.
Time Frame	Up to 28 days after the EDD of 40 0/7 weeks

Outcome Measure Data

Analysis Population Description

Neonatal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Fetal Death	0 0%	0 0%
Neonatal Death	0 0%	0 0%
RDS	3 23.1%	2 20%
Bronchopulmonary dysplasia	3 23.1%	0 0%
Necrotizing enterocolitis or Isolated Perforation	0 0%	0 0%
Sepsis	0 0%	0 0%
Meningitis	0 0%	0 0%
Retinopathy of prematurity	0 0%	0 0%
IVH	0 0%	0 0%
White Matter Injury	0 0%	0 0%
Cerebellar Hemorrhage	0 0%	0 0%

15. Secondary Outcome

Title	Number of Neonatal Participants With Admission to a Particular Hospital Unit
Description	Neonatal healthcare resource utilization was collected from review of medical records. The number of neonatal participants who were admitted to a particular hospital unit that is, level III (or higher) intensive neonatal care (NICU), Intensive care unit (ICU), general ward, Level I - Basic Neonatal care, Well born nursery (SCBU) and Level II-Special Care Newborn nursery high dependency (NHDU) has been summarized. Neonatal Safety Population consisted of neonates whose mothers received study treatment.
Time Frame	Up to 28 days post EDD (40 0/7 weeks gestation)

Outcome Measure Data

Analysis Population Description

Neonatal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Level III (or higher) NICU	5 38.5%	6 60%
Intensive care unit	0 0%	1 10%
General Ward	2 15.4%	2 20%
Level II-Special Care NHDU	0 0%	1 10%
Missing	1 7.7%	0 0%
Multiple ward type	5 38.5%	0 0%

16. Secondary Outcome

Title	Length of Stay in Specialized Care Unit
Description	Neonatal healthcare resource utilization was collected from review of medical records. The length of stay in a specialized care unit (NICU or ICU) has been presented for neonatal participants with admission to ICU or NICU.
Time Frame	Up to 28 days post EDD (40 0/7 weeks gestation)

Outcome Measure Data

Analysis Population Description

Neonatal Safety Population.

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	10	7
Mean (Standard Deviation) [Days]	40.34 (35.475)	35.60 (35.308)

17. Secondary Outcome

Title	Number of Newborn Participants With Hospital Readmission
Description	Newborn hospital readmission following hospitalization for birth was collected from the newborn's medical records. The number of newborn participants who had readmission to hospital is presented.
Time Frame	Up to 28 days of EDD (40 0/7 weeks gestation)

Outcome Measure Data

Analysis Population Description

Neonatal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	0 0%	0 0%

18. Secondary Outcome

Title	Length of Stay Following Readmission to Hospital
Description	Newborn hospital readmission following hospitalization for birth was collected from the newborn's medical records. Length of stay in hospital following readmission is presented for neonates.
Time Frame	Up to 28 days after EDD (40 0/7 weeks gestation)

Outcome Measure Data

Analysis Population Description

Neonatal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Median (Full Range) [Days]	0	0

19. Secondary Outcome

Title	Number of Participants With Ambulatory Surgery
Description	Information regarding participants who had ambulatory surgery was collected from the newborn medical records. The number of neonatal participants with ambulatory surgery is presented.
Time Frame	Up to 28 days post EDD (40 0/7 weeks gestation)

Outcome Measure Data

Analysis Population Description

Neonatal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	0 0%	0 0%

20. Secondary Outcome

Title	Time to Treatment Failure
Description	Treatment failure is defined as the administration of any putative tocolytic medication for treatment of preterm labor or as prophylaxis of preterm labor. Time to treatment failure is the number of days from the first dose of study treatment until treatment failure. The mean number of days to delivery or treatment failure along with standard deviation has been presented. Only those maternal participants with treatment failure were included in the analysis. NA indicates standard deviation could not be calculated as only one participant was analyzed.
Time Frame	Up to 17 weeks

Outcome Measure Data

Analysis Population Description

Maternal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	4	1
Mean (Standard Deviation) [Days]	1.141 (1.4307)	0.899 (NA)

21. Secondary Outcome

Title	Number of Participants Who Received Any Putative Tocolytic
Description	A putative tocolytic medication was the medication administered for active preterm labor or as prevention of preterm labor and included calcium channel blockers, nonsteroidal anti-inflammatory drugs, or beta agonists, or magnesium sulfate doses that exceeded prespecified IV loading doses, infusion rates, or total duration of administration.
Time Frame	Up to 17 weeks

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	4 30.8%	1 10%

22. Secondary Outcome

Title	Number of Participants With Subsequent Preterm Labor
Description	The participants who had not delivered after 48 hours post-infusion were contacted to determine if they had delivered or experienced any subsequent episodes of preterm labor. A subsequent episode of preterm labor was only recorded if the participant reported it to the Principal Investigator during one of the telephone follow-up calls but did not then go on to immediately deliver. However, if labor started and led to immediate delivery, then the only data collected would be the pre-specified delivery data and thus would not be counted as a subsequent episode of preterm labor. The number of participants who had a subsequent episode of preterm labor after administration of the study treatment has been presented. Maternal Safety Population comprised of all maternal participants randomly assigned to treatment who have been exposed to study treatment.
Time Frame	Up to 11 weeks

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	1 7.7%	1 10%

23. Secondary Outcome

Title	Number of Maternal Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that mey require medical or surgical intervention to prevent one of the other outcomes described before; is associated with liver injury and impaired liver function. Maternal Safety Population comprised of all mothers randomly assigned to treatment who have been exposed to study treatment. The number of maternal participants who experienced at least one AE and one SAE has been presented.
Time Frame	Up to 6 weeks after delivery

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
AEs	6 46.2%	6 60%
SAEs	0 0%	0 0%

24. Secondary Outcome

Title	Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Description	SBP and DBP were measured with participants in a semirecumbent or seated position. SBP and DBP were measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 9 days

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
DBP; Day 1: 15 to 30 minutes; n=13, 10	-3.2 (10.64)	-6.8 (8.22)
DBP; Day 1: 4 to 8 hours; n=11, 10	-9.0 (11.31)	-7.0 (10.14)
DBP; Day 1: 20 to 24 hours; n=10, 8	-13.1 (11.05)	-6.5 (8.65)
DBP; Day 2; n=11, 7	-10.2 (11.07)	-4.0 (6.66)
DBP; Post infusion assessment; n=9, 5	-6.6 (12.69)	-2.8 (4.76)
SBP; Day 1: 15 to 30 minutes; n=13, 10	-0.8 (7.50)	-3.1 (10.40)
SBP; Day 1: 4 to 8 hours; n=11, 10	-7.1 (13.09)	-1.3 (9.06)
SBP; Day 1: 20 to 24 hours; n=10, 8	-5.2 (12.47)	2.6 (14.56)
SBP; Day 2; n=11, 7	-4.5 (11.86)	0.7 (10.21)
SBP; Post infusion assessment; n=9, 5	-9.6 (8.69)	-7.0 (8.22)

25. Secondary Outcome

Title	Change From Baseline in Heart Rate
Description	Heart rate was measured with the participants in a semirecumbent or seated position. Heart rate was measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 9 days

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Day 1: 15 to 30 minutes; n=13, 10	-5.1 (12.37)	1.4 (8.13)
Day 1: 4 to 8 hours; n=11, 10	-2.6 (10.82)	-0.3 (8.12)
Day 1: 20 to 24 hours; n=9, 8	-4.1 (10.61)	6.5 (21.64)
Day 2; n=11, 7	-5.6 (15.73)	-3.6 (13.91)
Post infusion assessment; n=9, 5	-6.1 (17.80)	-3.8 (16.24)

26. Secondary Outcome

Title	Change From Baseline in Temperature
Description	Temperature was measured with the participants in a semirecumbent or seated position. Temperature was measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 1 week

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Day 1: 15 to 30 minutes; n=12, 9	-0.028 (0.4123)	-0.111 (0.1900)
Day 1: 4 to 8 hours; n=11, 10	0.087 (0.3947)	-0.144 (0.3594)
Day 1: 20 to 24 hours; n=10, 8	0.104 (0.5413)	-0.043 (0.3174)
Day 2; n=11, 7	0.105 (0.5067)	0.051 (0.2062)
Post-infusion assessment; n=9, 5	-0.136 (0.4668)	0.072 (0.2234)

27. Secondary Outcome

Title	Change From Baseline in Respiratory Rate
Description	Respiratory rate was measured with the participants in a semirecumbent or seated position. Respiratory rate was measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 1 week

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Day 1: 15 to 30 minutes; n=11, 8	0.5 (3.45)	-1.1 (2.90)
Day 1: 4 to 8 hours; n=8, 9	1.1 (3.83)	-1.1 (2.15)
Day 1: 20 to 24 hours; n=9, 7	0.3 (2.35)	-1.0 (2.77)
Day 2; n=10, 6	0.9 (4.01)	0.0 (1.79)
Post infusion assessment; n=8, 4	0.4 (4.27)	0.5 (2.52)

28. Secondary Outcome

Title	Change From Baseline in Hematocrit Levels
Description	Blood samples were collected for the evaluation of change in hematocrit levels from Baseline. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 1 week

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Day 2; n=9, 3	-0.0343 (0.04324)	-0.0470 (0.02773)
Post-infusion assessment; n=7, 5	-0.0090 (0.02900)	-0.0078 (0.02928)

29. Secondary Outcome

Title	Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC)
Description	Blood samples were collected for the evaluation of change in hemoglobin levels and MCHC from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 1 week

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Hemoglobin; Day 2; n=9, 3	-11.2 (11.20)	-15.7 (6.66)
Hemoglobin; Post-infusion assessment; n=7, 5	-1.0 (9.76)	-1.6 (8.79)
MCHC; Day 2; n=9, 3	-0.3 (17.27)	-2.7 (10.97)
MCHC; Post-infusion assessment; n=7, 5	5.0 (8.52)	2.6 (5.41)

30. Secondary Outcome

Title	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count
Description	Blood samples were collected for the evaluation of change in basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes count. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 1 week

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Basophils; Day 2; n=9, 3	-0.003 (0.0132)	0.000 (0.0458)
Basophils; post-infusion assessment; n=7, 5	0.003 (0.0160)	0.058 (0.1103)
Eosinophils; Day 2; n=9, 3	0.004 (0.0938)	-0.063 (0.0513)
Eosinophils; post-infusion assessment; 7, 5	0.064 (0.1321)	-0.044 (0.1328)
Lymphocytes; Day 2; n=9, 3	0.323 (0.6117)	0.877 (0.1914)
Lymphocytes; post-infusion assessment; 7, 5	0.253 (1.0579)	1.006 (1.4223)
Monocytes; Day 2; n=9, 3	0.008 (0.3389)	0.147 (0.5773)
Monocytes; post-infusion assessment; 7, 5	0.141 (0.2535)	-0.082 (0.4135)
Neutrophils; Day 2; n=9, 3	2.744 (6.9362)	-1.813 (3.3001)
Neutrophils; post-infusion assessment; 7, 5	-2.246 (6.0323)	-1.910 (2.8497)
Platelets; Day 2; n=8, 3	-6.4 (47.42)	-24.7 (32.58)
Platelets; post-infusion assessment; 6, 5	-15.7 (60.48)	-5.4 (33.34)
Leukocytes; Day 2; n=9, 3	3.10 (6.720)	-0.87 (2.914)
Leukocytes; post-infusion assessment; 7, 5	-1.76 (5.358)	-0.98 (2.645)

31. Secondary Outcome

Title	Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV)
Description	Blood samples were collected for the evaluation of change in MCV and MPV from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 1 week

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
MCV; Day 2; n=9, 3	0.4 (2.79)	1.7 (4.73)
MCV; Post-infusion assessment; n=7, 5	-1.9 (1.77)	-0.8 (1.30)
MPV; Day 2; n=8, 3	-0.11 (0.455)	-0.20 (0.436)
MPV; Post-infusion assessment; n=6, 5	0.02 (0.833)	0.48 (1.026)

32. Secondary Outcome

Title	Change From Baseline in Erythrocyte Level
Description	Blood samples were collected for the evaluation of change in erythrocyte level from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 1 week

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Day 2; n=9, 3	-0.39 (0.423)	-0.53 (0.153)
Post-infusion assessment; n=7, 5	-0.03 (0.330)	-0.02 (0.303)

33. Secondary Outcome

Title	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Levels
Description	Blood samples were collected for the evaluation of change in ALP, ALT, AST, GGT and LDH from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 1 week

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
ALP; Day 2; n=9, 5	-17.3 (17.56)	-11.8 (6.46)
ALP; post-infusion assessment; n=8, 6	6.6 (31.14)	-2.8 (14.08)
ALT; Day 2; n=9, 5	3.9 (19.60)	4.4 (10.64)
ALT; post-infusion assessment; n=8, 6	-8.8 (20.04)	2.5 (5.50)
AST; Day 2; n=9, 5	4.4 (15.69)	2.0 (10.20)
AST; post-infusion assessment; n=8, 6	-9.1 (13.05)	-0.5 (7.45)
GGT; Day 2; n=9, 5	-0.9 (1.69)	-0.8 (1.30)
GGT; post-infusion assessment; n=7, 5	4.4 (2.57)	0.4 (2.07)
LDH; Day 2; n=9, 5	-6.7 (33.51)	-26.4 (31.86)
LDH; post-infusion assessment; n=7, 5	-8.1 (21.93)	-7.6 (31.76)

34. Secondary Outcome

Title	Change From Baseline in Albumin and Protein Levels
Description	Blood samples were collected for the evaluation of change in albumin and protein levels from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 1 week

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Albumin; Day 2; n=9, 5	-3.4 (3.68)	-2.6 (1.67)
Albumin; post-infusion assessment; n=7, 5	-1.3 (2.21)	-1.0 (2.35)
Protein; Day 2; n=9, 5	-5.8 (6.26)	-5.4 (3.58)
Protein; post-infusion assessment; n=7, 5	-2.4 (3.41)	-1.8 (5.02)

35. Secondary Outcome

Title	Change From Baseline in Anion Gap, Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level
Description	Blood samples were collected for the evaluation of change from Baseline in levels of anion gap, calcium, chloride, carbon dioxide, glucose, potassium, magnesium, phosphate, and sodium. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 1 week

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Anion Gap; Day 2; n=8, 4	0.0 (4.72)	0.0 (1.83)
Anion Gap; post-infusion assessment; n=7, 4	-1.6 (5.26)	0.3 (2.22)
Calcium; Day 2; n=9, 5	-0.042 (0.2833)	-0.040 (0.1208)
Calcium; post-infusion assessment; n=7, 5	0.091 (0.2052)	-0.048 (0.1016)
Chloride; Day 2; n=9, 5	1.0 (5.17)	1.8 (2.17)
Chloride; post-infusion assessment; n=7, 5	-0.7 (3.35)	-0.6 (2.30)
Carbon Dioxide; Day 2; n=9, 5	-0.2 (3.63)	0.0 (2.35)
Carbon Dioxide; post-infusion assessment; n=7, 5	2.3 (3.64)	-0.2 (2.77)
Glucose; Day 2; n=9, 5	1.47 (1.639)	1.98 (1.064)
Glucose; post-infusion assessment; n=7, 5	0.11 (2.497)	0.28 (2.109)
Potassium; Day 2; n=9, 5	-0.16 (0.394)	0.10 (0.515)
Potassium; post-infusion assessment; n=7, 5	-0.16 (0.237)	0.10 (0.283)
Magnesium; Day 2; n=9, 5	-0.411 (0.9476)	-0.236 (0.5428)
Magnesium; post-infusion assessment; n=7, 5	-0.449 (0.6473)	-0.056 (0.6199)
Phosphate; Day 2; n=9, 5	-0.133 (0.1768)	0.030 (0.2928)
Phosphate; post-infusion assessment; n=7, 5	0.021 (0.2018)	0.110 (0.1557)
Sodium; Day 2; n=9, 5	1.4 (2.96)	0.4 (1.67)
Sodium; post-infusion assessment; n=7, 5	0.1 (2.12)	-0.8 (1.64)

36. Secondary Outcome

Title	Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels
Description	Blood samples were collected for the evaluation of change from Baseline in levels of direct bilirubin, bilirubin, indirect bilirubin, creatinine and urate. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline and up to 1 week

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Direct Bilirubin; Day 2; n=9, 5	0.0 (1.00)	-0.4 (0.89)
Direct Bilirubin; post-infusion assessment; n=7, 5	0.3 (0.76)	-0.4 (0.89)
Bilirubin; Day 2; n=9, 5	-0.7 (1.41)	-0.8 (1.10)
Bilirubin; post-infusion assessment; n=8, 6	-0.3 (1.28)	-2.0 (3.10)
Indirect Bilirubin; Day 2; n=9, 5	-0.7 (1.41)	-0.4 (1.67)
Indirect Bilirubin; post-infusion assessment;n=7,5	-0.6 (1.51)	-1.6 (3.85)
Creatinine; Day 2; n=6, 3	-0.33 (6.812)	2.37 (1.429)
Creatinine; post-infusion assessment; n=6, 3	1.92 (5.075)	-0.33 (2.695)
Urate; Day 2; n=9, 5	1.1 (24.72)	-22.0 (13.04)
Urate; post-infusion assessment; n=7, 5	12.9 (24.30)	-2.0 (40.25)

37. Secondary Outcome

Title	Number of Participants Who Discontinued Study Treatment Due to Clinical and Laboratory Toxicities
Description	Number of maternal participants who discontinued study treatment due to clinical and laboratory toxicities is presented.
Time Frame	Up to 48 hours post-infusion

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	0 0%	0 0%

38. Secondary Outcome

Title	Number of Maternal Participants With a Score of 12 or Higher on the Edinburgh Postnatal Depression Scale (EPDS)
Description	The effect of preterm birth on maternal health status was assessed using the EPDS. The EPDS is a 10-item self-reported assessment of depression, validated for administration during both the antenatal and the post-natal periods. Items are rated on a 4-point variable Likert scale, ranging from 0 to 3. The total score was calculated by adding individual scores for each item and ranged from 0 to 30. A score of less than 8 indicates depression not likely; score of 9 to 11 indicates possible depression and a score of more than 12 indicates an increased probability of depression. Maternal participants were required to complete the EPDS at the maternal follow-up assessment 6 weeks post-delivery.
Time Frame	Up to 6 weeks post delivery

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	2 15.4%	0 0%

39. Secondary Outcome

Title	Number of Maternal Participants With AEs of Special Interest (AESI).
Description	Maternal AESI included: maternal death; chorioamnionitis and its complications (clinical chorioamnionitis, preterm premature rupture of membranes, endomyometritis, wound infection, pelvic abscess, bacteremia, septic shock, disseminated intravascular coagulation, and adult RDS); placental abruption; postpartum hemorrhage - postpartum hemorrhage and/or retained placenta and pulmonary edema. The number of participants with at least one AESI has been presented.
Time Frame	Up to 6 weeks post-delivery

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	0 0%	1 10%

40. Secondary Outcome

Title	Number of Maternal Participants With Disease Related AEs (DRE)
Description	Maternal DREs included: signs and symptoms of labor discomfort (example, cramping, backache, muscle aches, nausea); subsequent episodes of preterm labor and hospitalization for delivery. The number of participants with at least one DRE has been presented.
Time Frame	Up to 6 weeks post-delivery

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	0 0%	1 10%

41. Secondary Outcome

Title	Number of Fetal Participants With AEs and SAEs Prior to Delivery
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the other outcomes described before; is associated with liver injury and impaired liver function. Fetal AEs and SAEs included the adverse events that were experienced by the fetus prior to delivery. The number of fetal participants who experienced at least one AE and one SAE has been presented.
Time Frame	Up to 17 weeks post-infusion

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
AE	3 23.1%	5 50%
SAE	0 0%	1 10%

42. Secondary Outcome

Title	Number of Participants With Fetal Acidosis
Description	The number of participants with fetal acidosis is presented.
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	0 0%	0 0%

43. Secondary Outcome

Title	Number of Participants With Fetal AESI
Description	Fetal AESI included: intrauterine fetal demise; category II or III fetal heart rate tracing; and fetal inflammatory response syndrome characterized by cord blood interleukin-6 >11 picogram per milliliter (pg/mL), funisitis, or chorionic vasculitis. The number of participants who experienced at least one AESI has been presented.
Time Frame	Up to 17 weeks

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	3 23.1%	5 50%

44. Secondary Outcome

Title	Neonatal APGAR Scores
Description	APGAR is a quick test to assess the health of new born children. The test is performed at 1 and 5 minutes after birth. APGAR scale is determined by evaluating the new born on five categories (appearance, pulse, grimace, activity and respiration) on a scale from zero to two, then summing up the five values obtained. APGAR score ranges from 0 to 10 where a score of 7 and above is normal. The mean and standard deviation of APGAR scores at one minute and at five minutes of birth has been presented.
Time Frame	Up to 5 minutes after birth

Outcome Measure Data

Analysis Population Description

Neonatal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
one minute at birth	7.3 (1.80)	7.5 (1.78)
five minutes at birth	8.5 (1.05)	8.7 (1.06)

45. Secondary Outcome

Title	Weight of Neonates
Description	The weight of neonates was obtained from the neonate birth record. The mean weight of neonates and standard deviation has been presented.
Time Frame	Up to 17 weeks

Outcome Measure Data

Analysis Population Description

Neonatal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Mean (Standard Deviation) [grams (g)]	2015.0 (805.67)	2121.2 (681.31)

46. Secondary Outcome

Title	Head Circumference of Neonates
Description	The head circumference was determined from the neonate birth record.
Time Frame	Up to 17 weeks

Outcome Measure Data

Analysis Population Description

Neonatal ITT Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period
Measure Participants	13	10
Mean (Standard Deviation) [centimeters (cm)]	29.57 (2.791)	30.13 (3.059)

47. Secondary Outcome

Title	Number of Neonatal Participants With AEs and SAEs
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the other outcomes described before; is associated with liver injury and impaired liver function. The number of participants who experienced at least one AE and one SAE has been presented. Neonatal Safety Population consisted of neonates whose mothers received randomized treatment.
Time Frame	Up to 28 days after the EDD of 40 weeks gestation

Outcome Measure Data

Analysis Population Description

Neonatal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
AEs	8 61.5%	7 70%
SAEs	3 23.1%	5 50%

48. Secondary Outcome

Title	Number of Neonatal Participants With AESI
Description	Neonatal AESI included: Neonatal death; Asphyxia; Infections (early onset neonatal sepsis, septic shock, pneumonia, meningitis); RDS; Hypotension; IVH/periventricular leukomalacia; Bronchopulmonary dysplasia; Neonatal acidosis; Hyperbilirubinemia; Necrotizing enterocolitis; and Hypoxic ischemic encephalopathy. The number of neonatal participants who experienced at least one AESI has been presented.
Time Frame	Up to 28 days after EDD of 40 weeks gestation

Outcome Measure Data

Analysis Population Description

Neonatal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	8 61.5%	5 50%

49. Secondary Outcome

Title	Number of Neonatal Participants With DRE
Description	The disease related neonatal events occurring in Infants born prior to 37 completed weeks included: apnea (severe), respiratory failure due to fatigue, hypoxia, or air leak from alveolar injury, patent ductus arteriosus, bradycardia, ventriculomegaly, cerebellar hemorrhage, hydrocephalus other than congenital, gastroesophageal reflux, aspiration pneumonia, anemia, retinopathy of prematurity (all stages), hearing disorder, temperature instability and hypoglycemia. The number of participants with at least one DRE has been presented.
Time Frame	Up to 28 days after EDD of 40 weeks gestation

Outcome Measure Data

Analysis Population Description

Neonatal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, intravenous (IV) loading dose over 5 minutes and continuous infusion rate for remainder of 48-hour treatment period.Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Number [Participants]	4 30.8%	2 20%

50. Secondary Outcome

Title	Maternal Length of Stay in Hospital
Description	Details on maternal health care resource use (both for hospitalizations related to preterm labor not resulting in a delivery and hospitalizations related to preterm labor/normal labor resulting in a delivery) associated with an episode of preterm labor, preterm delivery and normal term delivery (>= 37 weeks gestation) were collected from review of medical records. Length of hospital stay associated with hospital admission for preterm labor and normal term labor/term delivery is presented. One participant in the retosiban arm did not have hospitalization data; hence, was excluded from the analysis at delivery. Only participants with data available at the specified time points were analyzed (indicated by n=X) in category titles. NA indicates standard deviation could not be calculated as only one participant was analyzed.
Time Frame	Up to 28 days post EDD (40 0/7 weeks gestation)

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Preterm labor; n=1, 0	2.642 (NA)
Preterm delivery; n=9, 7	10.177 (11.9312)	13.583 (20.7670)
Normal term delivery; n=4, 2	3.719 (2.2309)	4.635 (2.7616)

51. Secondary Outcome

Title	Number of Participants With Hospital Admissions Related to Preterm Labor and Preterm Delivery
Description	Maternal healthcare resource utilization associated with an episode of preterm labor and preterm delivery were collected from the review of medical records. One participant in the retosiban arm did not have hospitalization data; hence, was excluded from the analysis at delivery. The number of participants who had hospital admission for preterm labor and preterm delivery has been presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
Time Frame	Up to 28 days after EDD (40 0/7 weeks of gestation)

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Preterm labor; n=13, 10	1 7.7%	0 0%
Preterm delivery; n=13, 9	9 69.2%	7 70%

52. Secondary Outcome

Title	Number of Participants Admitted to Particular Hospital Unit
Description	Maternal healthcare resource utilization associated with an episode of preterm labor, preterm delivery and normal term delivery were collected from the review of medical records. The number of participants who were admitted to a particular hospital unit has been presented.
Time Frame	Up to 28 days post EDD (40 0/7 weeks gestation)

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
General ward	9 69.2%	2 20%
Private/Semi-private room	3 23.1%	2 20%
Labor and delivery	2 15.4%	3 30%
Labor and delivery to post-partum	0 0%	1 10%
Post-partum	0 0%	1 10%
Ward not specified	0 0%	1 10%
Labor ward	0 0%	1 10%
Antenatal ward	0 0%	1 10%
Postnatal ward	0 0%	1 10%

53. Secondary Outcome

Title	Number of Participants With Different Modes of Transportation to Hospital
Description	The means by which the maternal participants were transported to the hospital i.e. ground ambulance/emergency vehicle (gr. amb/emer. veh), air ambulance, family member or other means were obtained from the review of medical records. The number of maternal participants with the corresponding mode of transportation is presented for preterm labor visit and delivery visit. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
Time Frame	Up to 28 days post EDD (40 0/7 weeks gestation)

Outcome Measure Data

Analysis Population Description

Maternal Safety Population

Arm/Group Title	Placebo	Retosiban
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	13	10
Preterm labor; gr. amb/emer. veh; n=1, 0	0 0%
Preterm labor; air ambulance; n=1, 0	0 0%
Preterm labor; family member; n=1, 0	1 7.7%
Preterm labor; other; n=1, 0	0 0%
Delivery; gr. amb/emer. veh; n=5, 5	2 15.4%	1 10%
Delivery; air ambulance; n=5, 5	0 0%	0 0%
Delivery; family member; n=5, 5	3 23.1%	3 30%
Delivery; other; n=5, 5	0 0%	1 10%
Preterm labor;<24 hour stay;gr. amb/emer.veh;n=1,0	0 0%
Preterm labor; <24 hour stay;air ambulance; n=1, 0	0 0%
Preterm labor; <24 hour stay;family member; n=1, 0	1 7.7%
Preterm labor; <24 hour stay;other; n=1, 0	0 0%

54. Secondary Outcome

Title	Retosiban Clearance
Description	Maternal blood samples were collected at the indicated time points for pharmacokinetic analysis. Data is a combined data set. Data is presented for 10 participants from retosiban arm of study 200719 (NCT02377466) and 43 participants from retosiban arm of study 200721 (NCT02292771).
Time Frame	Day 1 (2 to 4 hours, 10 to 14 hours) and Day 2 (22 to 26 hours, and 48 to 54 hours) post-infusion

Outcome Measure Data

Analysis Population Description

Maternal Safety Population. Data is a combined data set. Data is presented for 10 participants from retosiban arm of study 200719 (NCT02377466) and 43 participants from retosiban arm of study 200721 (NCT02292771).

Arm/Group Title	Retosiban
Arm/Group Description	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	53
Geometric Mean (Geometric Coefficient of Variation) [Liters per hour]	83.4 (5.25)

55. Secondary Outcome

Title	Volume of Distribution of Retosiban
Description	Maternal blood samples were collected at the indicated time points for pharmacokinetic analysis. Data is a combined data set. Data is presented for 10 participants from retosiban arm of study 200719 (NCT02377466) and 43 participants from retosiban arm of study 200721 (NCT02292771).
Time Frame	Day 1 (2 to 4 hours, 10 to 14 hours) and Day 2 (22 to 26 hours, and 48 to 54 hours) post-infusion

Outcome Measure Data

Analysis Population Description

Maternal Safety Population. Data is a combined data set. Data is presented for 10 participants from retosiban arm of study 200719 (NCT02377466) and 43 participants from retosiban arm of study 200721 (NCT02292771).

Arm/Group Title	Retosiban
Arm/Group Description	Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
Measure Participants	53
Geometric Mean (Geometric Coefficient of Variation) [Liters]	68.6 (109)

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) will be collected from the start of study treatment and until the follow up contact (Up to 6 weeks after delivery).
Adverse Event Reporting Description	SAEs and AEs were analyzed in Maternal Safety Population and Neonatal Safety Population which comprised of mothers randomly assigned to treatment who were exposed to study treatment and neonates whose mothers received randomized treatment.
Arm/Group Title	Placebo (Maternal)		Retosiban (Maternal)		Placebo (Fetal)		Retosiban (Fetal)		Placebo (Neonatal)		Retosiban (Neonatal)
Arm/Group Description	Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.		Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.		Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.		Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.		Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, 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.		Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/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/hour continuous infusion for remainder of 48-hour treatment period.
All Cause Mortality
	Placebo (Maternal)		Retosiban (Maternal)		Placebo (Fetal)		Retosiban (Fetal)		Placebo (Neonatal)		Retosiban (Neonatal)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Serious Adverse Events
	Placebo (Maternal)		Retosiban (Maternal)		Placebo (Fetal)		Retosiban (Fetal)		Placebo (Neonatal)		Retosiban (Neonatal)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/10 (0%)		0/13 (0%)		1/10 (10%)		3/13 (23.1%)		5/10 (50%)
Cardiac disorders
Cardiac arrest	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Congenital, familial and genetic disorders
Ankyloglossia congenital	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		1/10 (10%)
Congenital hypothyroidism	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		1/10 (10%)
Gastrointestinal disorders
Inguinal hernia	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		2/10 (20%)
Meconium plug syndrome	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Infections and infestations
Group B streptococcus neonatal sepsis	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		1/10 (10%)
Tracheitis	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		1/10 (10%)
Pregnancy, puerperium and perinatal conditions
Umbilical cord prolapse	0/13 (0%)		0/10 (0%)		0/13 (0%)		1/10 (10%)		0/13 (0%)		0/10 (0%)
Psychiatric disorders
Selective eating disorder	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Neonatal respiratory distress syndrome	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		2/13 (15.4%)		1/10 (10%)
Other (Not Including Serious) Adverse Events
	Placebo (Maternal)		Retosiban (Maternal)		Placebo (Fetal)		Retosiban (Fetal)		Placebo (Neonatal)		Retosiban (Neonatal)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/13 (46.2%)		6/10 (60%)		3/13 (23.1%)		5/10 (50%)		8/13 (61.5%)		7/10 (70%)
Blood and lymphatic system disorders
Anaemia	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Thrombocytopenia	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		1/10 (10%)
Cardiac disorders
Foetal heart rate disorder	0/13 (0%)		0/10 (0%)		2/13 (15.4%)		5/10 (50%)		0/13 (0%)		0/10 (0%)
Foetal heart rate deceleration abnormality	0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Eye disorders
Conjunctival haemorrhage	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		1/10 (10%)
Gastrointestinal disorders
Constipation	1/13 (7.7%)		1/10 (10%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Abdominal discomfort	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Diarrhoea	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Haemorrhoids	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Inguinal hernia	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		2/13 (15.4%)		2/10 (20%)
Haematochezia	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		1/10 (10%)
Necrotising colitis	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Vomiting	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
General disorders
Oedema	0/13 (0%)		1/10 (10%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Pyrexia	0/13 (0%)		1/10 (10%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Granuloma	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia neonatal	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		6/13 (46.2%)		4/10 (40%)
Jaundice	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		1/10 (10%)
Cholestasis	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Infections and infestations
Abscess limb	0/13 (0%)		1/10 (10%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Amniotic cavity infection	0/13 (0%)		1/10 (10%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Bacterial vulvovaginitis	0/13 (0%)		1/10 (10%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Kidney infection	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Viral upper respiratory tract infection	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Device related infection	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Oral candidiasis	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		1/10 (10%)
Injury, poisoning and procedural complications
Contusion	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		1/10 (10%)
Vaccination complication	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Investigations
Blood calcium decreased	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Blood glucose decreased	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Liver function test increased	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Body temperature fluctuation	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Metabolism and nutrition disorders
Feeding intolerance	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Hypoglycaemia	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Pain in extremity	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Osteopenia	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Nervous system disorders
Headache	1/13 (7.7%)		1/10 (10%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Intraventricular haemorrhage	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Motor dysfunction	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Pregnancy, puerperium and perinatal conditions
Oligohydramnios	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Uterine contractions abnormal	0/13 (0%)		1/10 (10%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Reproductive system and breast disorders
Oedema genital	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/13 (0%)		1/10 (10%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Neonatal respiratory distress syndrome	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		2/13 (15.4%)		2/10 (20%)
Bronchopulmonary dysplasia	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		3/13 (23.1%)		0/10 (0%)
Pleural effusion	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Respiratory acidosis	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Tachypnoea	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Pruritus	0/13 (0%)		1/10 (10%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Pruritus generalised	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Dermatitis diaper	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Dry skin	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Intertrigo	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Seborrhoea	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)
Vascular disorders
Hypertension	1/13 (7.7%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)
Hypotension	0/13 (0%)		0/10 (0%)		0/13 (0%)		0/10 (0%)		1/13 (7.7%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.