Status
Terminated
Phase
Phase 3
Enrollment
97
Locations
21
Results
Posted
Publications
0
Study summary
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.
Interventions
DRUG
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
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
A placebo infusion containing 0.9% sodium chloride (NaCl) matched for retosiban loading (bolus) dose and continuous infusion.
DRUG
A placebo infusion containing 0.9% NaCl matched for the atosiban loading (bolus) dose and continuous infusion.
Timeline
First posted
Nov 17, 2014
Study start
Mar 16, 2015
Primary completion
Aug 25, 2017
Study completion
Aug 25, 2017
Results posted
Sep 10, 2018
Registry updated
Jul 29, 2020
Outcomes
Time to Delivery From the Start of Investigational Product (IP) Administration
Time frame · Up to 17 weeks
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.
Number of Participants With Births Prior to 37 0/7 Weeks Gestation
Time frame · Up to 13 weeks
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.
Number of Participants With Births at Term
Time frame · 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. Logistic regression model was used to calculate p-values.
Length of Neonatal Hospital Stay
Time frame · Up to 28 days post estimated date of delivery (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. 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.
Number of Neonates With Composite Neonatal Morbidity and Mortality
Time frame · 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, 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.
Number of Neonates With Any Composite Neonatal Morbidity and Mortality, Excluding RDS
Time frame · 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, 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.
Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality
Time frame · 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, 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.
Length of Stay in Specialized Care Unit
Time frame · Up to 28 days post EDD (40 0/7 weeks gestation)
Length of neonatal stay in specialized care unit like Intensive Care Unit (ICU) or Neonatal Intensive Care Unit (NICU) are reported.
Number of Newborn Participants With Hospital Readmission
Time frame · Up to 28 days of EDD (40 0/7 weeks gestation)
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.
Number of Participants With Births Prior to 28 0/7 Weeks Gestation
Time frame · 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.
Number of Participants With Births Prior to 32 0/7 Weeks Gestation
Time frame · Up to 8 weeks
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.
Eligibility
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 locations
Belgium · Germany · Israel · Italy · Mexico · South Korea · Spain · Sweden · United Kingdom. Showing up to 24 locations stored in the fast local snapshot.
GSK Investigational Site
Bruges, Belgium
GSK Investigational Site
Brussels, Belgium
GSK Investigational Site
Freiburg im Breisgau, Baden-Wurttemberg, Germany
GSK Investigational Site
Jena, Thuringia, Germany
GSK Investigational Site
Hamburg, Germany
GSK Investigational Site
Haifa, Israel
GSK Investigational Site
Holon, Israel
GSK Investigational Site
Kfar Saba, Israel
GSK Investigational Site
Petah Tikva, Israel
GSK Investigational Site
Safed, Israel
GSK Investigational Site
Tel Aviv, Israel
GSK Investigational Site
Siena, Tuscany, Italy
GSK Investigational Site
Monza, Italy
GSK Investigational Site
Monterrey, Nuevo León, Mexico
GSK Investigational Site
Ciudad Obregón, Sonora, Mexico
GSK Investigational Site
Seoul, South Korea
GSK Investigational Site
Seoul, South Korea
GSK Investigational Site
Sungnam, South Korea
GSK Investigational Site
Zaragoza, Spain
GSK Investigational Site
Uppsala, Sweden
GSK Investigational Site
Sheffield, United Kingdom
Publications
No PMID-linked publications were present in this registry snapshot.
Related trials
Northwest Women's and Children's Hospital, Xi'an, Shaanxi · Infertility
Not applicable
Recruiting
792
2025-12
University of Electronic Science and Technology of China · Healthy Adult Male
Early Phase 1
Recruiting
250
2025-09
University of Electronic Science and Technology of China · Healhty
Early Phase 1
Recruiting
250
2025-07
Children's Hospital of Chongqing Medical University · Cervical Cerclage · Premature Birth
Not applicable
Completed
334
2025-05
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Preterm Birth
Phase 4
Completed
760
2024-07
University of Sao Paulo General Hospital · Myelomeningocele · Terbutaline Adverse Reaction
Not applicable
Completed
25
2022-06
Radboud University Medical Center · Endometriosis
Phase 2
Unknown
10
2022-05
Al Baraka Fertility Hospital · Recurrent Implantation Failure
Not applicable
Unknown
150
2021-09
Related PeptideStat pages
Research pages describe evidence. Vendor pages, where available, describe independently tracked research-product listings and are not clinical recommendations.