A Randomized Study Comparing the Efficacy and Safety of Retosiban Versus Atosiban for Women in Spontaneous Preterm Labour

Randomized, Double-blind, Multicenter, Phase III Study Comparing the Efficacy and Safety of Retosiban Versus Atosiban Therapy for Women in Spontaneous Preterm Labor

The primary objective of this study is to demonstrate the superiority of retosiban to prolong pregnancy in females with spontaneous preterm labor compared with atosiban. This objective is based on the hypothesis that prolonging the time to delivery in the absence of harm may benefit the newborn, particularly in women who experience spontaneous preterm labor at early gestational ages (GA). This study is designed to test this hypothesis through a direct comparison with atosiban, a mixed oxytocin vasopressin antagonist indicated for short-term use to delay imminent preterm birth in women between 24^0/7 and 33^6/7 weeks' gestation in preterm labor. This is a randomized, double-blind, double-dummy study, which consists of 6 phases: Screening, Inpatient Randomized Treatment, Post Infusion Assessment, Delivery, Maternal Post Delivery Assessment, and Neonatal Medical Review. Approximately 330 females will be randomly assigned to retosiban or atosiban treatment in a 1:1 ratio. The duration of any one subject's (maternal or neonatal) participation in the study will be variable and dependent on GA at study entry and the date of delivery.

Study Overview

• Status: Terminated
• Conditions: Obstetric Labour, Premature
• Intervention / Treatment: Drug: Retosiban; Drug: Placebo matching atosiban; Drug: Atosiban; Drug: Placebo matching retosiban

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium, 8000
    • GSK Investigational Site
  • Bruxelles, Belgium, 1200
    • GSK Investigational Site
• Germany
  • Hamburg, Germany, 22087
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Freiburg, Baden-Wuerttemberg, Germany, 79106
      • GSK Investigational Site
  • Thueringen
    • Jena, Thueringen, Germany, 07743
      • GSK Investigational Site
• Israel
  • Haifa, Israel, 31048
    • GSK Investigational Site
  • Holon, Israel, 58100
    • GSK Investigational Site
  • Kfar Saba, Israel, 44281
    • GSK Investigational Site
  • Petach Tikva, Israel, 49100
    • GSK Investigational Site
  • Safed, Israel, 13100
    • GSK Investigational Site
  • Tel Aviv, Israel, 64239
    • GSK Investigational Site
• Italy
  • Monza, Italy, 20052
    • GSK Investigational Site
  • Toscana
    • Siena, Toscana, Italy, 53100
      • GSK Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 135-081
    • GSK Investigational Site
  • Sungnam, Korea, Republic of, 463712
    • GSK Investigational Site
• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • GSK Investigational Site
  • Sonora
    • Ciudad Obregon, Sonora, Mexico, 85000
      • GSK Investigational Site
• Spain
  • Zaragoza, Spain, 50009
    • GSK Investigational Site
• Sweden
  • Uppsala, Sweden, SE-75185
    • GSK Investigational Site
• United Kingdom
  • Sheffield, United Kingdom, S10 2JF
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 labor (Note: This protocol includes pregnant adolescents, aged 12 to 17 years, as appropriate, based on national or local regulations.).
• Gestational age between 24^0/7 and 33^6/7 weeks as determined by known fertilization date, either in vitro fertilization or intrauterine insemination, last menstrual period confirmed by the earliest ultrasound prior to 24^0/7 weeks' gestation, or the earliest ultrasound alone prior to 24^0/7 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.
• Subjects must be diagnosed with preterm labor according to both of the following criteria:

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:

Cervical dilation >=2 centimeter (cm) and <=4 cm by digital cervical examination or If <2 cm dilation by digital cervical examination, a cervical change consisting of an increase of at least 25% effacement or 1 cm dilation

• Treatment naïve subjects and subjects not adequately responding to tocolytics other than atosiban (e.g., transfers from other care units) during their current episode of preterm labor may be eligible for the study. Historical failure of a tocolytic treatment in a previous episode of preterm labor is not a required inclusion criterion. Tocolytic failure is defined by progressive cervical changes or continuing uterine contractions.

Exclusion Criteria:

• Fever with a temperature greater than 100.4°fahrenheit (F) (38°Celcius [C]) for more than 1 hour or >=101°F (38.3°C) 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 (e.g., 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 (amniotic fluid index [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, 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 or urine drug screen findings suggestive of substance abuse that may either be implicated as the cause of preterm labor (e.g., abuse of cocaine or methamphetamines) or have the potential to complicate the pregnancy outcome (e.g., alcohol abuse or opioid addiction).
• 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.
• Women with documented active hepatitis B or hepatitis C viral infection, unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of sensitivity to the IPs or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK)/PPD medical monitor, contraindicates their participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Retosiban + Atosiban Placebo; Participants will receive retosiban 6 milligrams (mg) intravenous (IV) loading dose over 5 minutes, followed by a 6mg/hour continuous infusion over 48 hours. For subjects with an inadequate response after the first hour of treatment, investigators will administer another 6mg IV loading dose and increase the infusion rate to 12 mg/hour for the remainder of the 48-hour treatment period. Participants will also receive placebo infusion matched for the atosiban loading (bolus) dose and continuous infusion to ensure blinding.	Drug: Retosiban; Solution for infusion, consisting of a clear colorless solution of retosiban at a concentration of 15 milligram/milliliter (mg/mL) in 56% volume/volume ethanol/acetate buffer concentrate supplied in 5 mL vial containing 75mg retosiban.; Drug: Placebo matching atosiban; A placebo infusion containing 0.9% NaCl matched for the atosiban loading (bolus) dose and continuous infusion.
Active Comparator: Atosiban + Retosiban Placebo; Participants will receive atosiban in 3 successive stages: an initial bolus dose (6.75 mg) over 1 minute, immediately followed by a continuous infusion at 18 mg/hour for 3 hours, followed by a 6 mg/hour infusion for the remainder of the 48-hour treatment period. Participants will also receive placebo infusion matched for retosiban loading (bolus) dose and continuous infusion to ensure blinding.	Drug: Atosiban; Clear, colorless solution for injection in a 0.9-mL vial containing 6.75 mg of atosiban. Clear, colorless concentrate for solution for infusion in a 5-mL vial containing 37.5 mg atosiban.; Drug: Placebo matching retosiban; A placebo infusion containing 0.9% sodium chloride (NaCl) matched for retosiban loading (bolus) dose and continuous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Delivery From the Start of Investigational Product (IP) Administration	Time to delivery is the number of days from the first dose of study treatment until delivery. 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 adjusted mean number of days to delivery along with standard error has been presented. 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.	Up to 17 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Births Prior to 37 0/7 Weeks Gestation	Gestational age (GA) at birth (weeks) is defined as the GA when the baby is born. Participants were considered to have delivered prior to 37 0/7 weeks, that is preterm , if the GA 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. Logistic regression model was used to calculate p-values.	Up to 13 weeks
Number of Participants With Births at Term	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. Logistic regression model was used to calculate p-values.	Up to 17 weeks
Length of Neonatal Hospital Stay	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. Log of length of stay was calculated as treatment plus GA at randomization plus established progesterone use based on Analysis of covariance (ANCOVA) model. The p-value was calculated using t-test method. 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.	Up to 28 days post estimated date of delivery (EDD) of 40 0/7 weeks gestation
Number of Neonates With Composite Neonatal Morbidity and Mortality	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 (BPD), necrotizing enterocolitis (NEC) 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 (ROP), Intraventricular Hemorrhage (IVH), white matter injury and cerebellar hemorrhage.	Up to 28 weeks after EDD (40 weeks gestation)
Number of Neonates With Any Composite Neonatal Morbidity and Mortality, Excluding RDS	The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, RDS, BPD, NEC 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, ROP, IVH, white matter injury and cerebellar hemorrhage. Number of neonates with any composite neonatal morbidity and mortality component, excluding RDS has been presented.	Up to 28 weeks after EDD (40 weeks gestation)
Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality	The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, RDS, BPD, NEC 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, ROP, IVH, cerebellar hemorrhage and white matter injury included Periventricular Leukomalacia PVL), porencephalic cyst, and persistent ventriculomegaly. Number of neonates with with each individual component of the composite neonatal morbidity and mortality has been presented.	Up to 28 weeks after EDD (40 weeks gestation)
Length of Stay in Specialized Care Unit	Length of neonatal stay in specialized care unit like Intensive Care Unit (ICU) or Neonatal Intensive Care Unit (NICU) are reported.	Up to 28 days post EDD (40 0/7 weeks gestation)
Number of Newborn Participants With Hospital Readmission	Newborn hospital readmission following hospitalization for birth was obtained from the newborn's medical records. Only those participants with data available at the specified data points were analyzed.	Up to 28 days of EDD (40 0/7 weeks gestation)
Number of Participants With Births Prior to 28 0/7 Weeks Gestation	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.	Up to 4 weeks
Number of Participants With Births Prior to 32 0/7 Weeks Gestation	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.	Up to 8 weeks
Number of Participants With Births Prior to 35 0/7 Weeks Gestation	Number of participants who delivered prior to 35 0/7 weeks gestation has been presented. Only those maternal participants who were randomized prior to 35 0/7 week's gestation and delivered were included.	Up to 11 weeks
Number of Participants With Births <=7 Days From the First Study Treatment	Number of participants who delivered in less than or equal to 7 days from first dose of study treatment has been presented.	Up to 7 days
Number of Participants With Births <=48 Hours From the First Study Treatment	Number of participants who delivered in less than or equal to 48 hours from first dose of study treatment has been presented.	Up to 48 hours
Number of Participants With Births <=24 Hours From the First Study Treatment	Number of participants who delivered in less than or equal to 24 hours from first dose of study treatment has been presented.	Up to 24 hours
Number of Maternal Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	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. 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 non-serious AE and one SAE has been presented.	Up to 6 weeks after delivery
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants	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).	Baseline and up to 1 week
Change From Baseline in Heart Rate in Maternal Participants	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).	Baseline and up to 1 week
Change From Baseline in Respiratory Rate in Maternal Participants	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).	Baseline and up to 1 week
Change From Baseline in Temperature in Maternal Participants	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).	Baseline and up to 1 week
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants	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). NA indicates standard deviation was not calculable for a single data point.	Baseline and up to 1 week
Change From Baseline in Erythrocytes in Maternal Participants	Blood samples were collected for the evaluation of change in erythrocytes 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). NA indicates standard deviation was not calculable for a single data point.	Baseline and up to 1 week
Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants	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. NA indicates standard deviation was not calculable for a single data point.	Baseline and up to 1 week
Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants	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). NA indicates standard deviation was not calculable for a single data point.	Baseline and up to 1 week
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Levels in Maternal Participants	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). NA indicates standard deviation was not calculable for a single data point.	Baseline and up to 1 week
Change From Baseline in Albumin and Protein Levels in Maternal Participants	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). NA indicates standard deviation was not calculable for a single data point.	Baseline and up to 1 week
Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants	Blood samples were collected for the evaluation of change from Baseline in levels of 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). NA indicates standard deviation was not calculable for a single data point.	Baseline and up to 1 week
Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants	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). NA indicates standard deviation was not calculable for a single data point.	Baseline and up to 1 week
Number of Maternal Participants With AEs of Special Interest (AESI)	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.	Up to 6 weeks post-delivery
Number of Maternal Participants With Disease Related AEs (DRE)	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.	Up to 6 weeks post-delivery
Number of Participants With Fetal Non-serious AEs and SAEs	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 non-serious AE and one SAE has been presented.	Up to 17 weeks
Number of Participants With Fetal AESI	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.	Up to 17 weeks
Neonatal APGAR Scores	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.Only those participants with data available at the specified data points were analyzed.	Up to 5 minutes after birth
Weight of Neonates	The weight of neonates was obtained from the neonate birth record. The mean weight of neonates and standard deviation has been presented. Only those participants with data available at the specified data points were analyzed.	Up to 17 weeks
Head Circumference of Neonates	The head circumference was determined from the neonate birth record. Only those participants with data available at the specified data points were analyzed.	Up to 17 weeks
Number of Neonatal Participants With Non-serious AEs and SAEs	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 non-serious AE and one SAE has been presented. Neonatal Safety Population consisted of neonates whose mothers received randomized treatment.	Up to 28 days after the EDD of 40 weeks gestation
Number of Neonatal Participants With AESI	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.	Up to 28 days after EDD of 40 weeks gestation
Number of Neonatal Participants With DRE	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.	Up to 28 days after EDD of 40 weeks gestation
Maternal Length of Stay in Hospital	The length of hospital stay associated with hospital admission for preterm labor and term labor/term delivery was collected from review of medical records. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Up to 28 days post EDD (40 0/7 weeks gestation)
Number of Participants Admitted to Particular Hospital Unit	Maternal healthcare resource utilization associated with an episode of preterm labor and normal term delivery were collected from the review of medical records. The number of participants who were admitted to a particular hospital unit like general ward, private/semi-private room, recovery, and other has been presented.	Up to 28 days post EDD (40 0/7 weeks gestation)
Retosiban Clearance	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).	Day 1 (2 to 4 hours, 10 to 14 hours) and Day 2 (22 to 26 hours, and 48 to 54 hours) post-infusion
Volume of Distribution of Retosiban	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).	Day 1 (2 to 4 hours, 10 to 14 hours) and Day 2 (22 to 26 hours, and 48 to 54 hours) post-infusion

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: PPD

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2015
• Primary Completion (Actual): August 25, 2017
• Study Completion (Actual): August 25, 2017

Study Registration Dates

• First Submitted: November 13, 2014
• First Submitted That Met QC Criteria: November 13, 2014
• First Posted (Estimate): November 17, 2014

Study Record Updates

• Last Update Posted (Actual): July 29, 2020
• Last Update Submitted That Met QC Criteria: July 14, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Spontaneous Preterm Labor; retosiban; GSK221149; atosiban
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Reproductive Control Agents; Oxytocics; Tocolytic Agents; Vasoconstrictor Agents; Vasotocin; Atosiban
• Other Study ID Numbers: 200721; 2014-001826-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No