preterm labor MedDRA version: 19.1 Level: PT Classification code 10036595 Term: Premature delivery System Organ Class: 10036585 - Pregnancy, puerperium and perinatal conditions
Conditions
Interventions
Product Name: Retosiban
Product Code: GSK221149
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Retosiban
CAS Number: 820957-38-8
Current Sponsor code: GSK221149A
Other descr
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Signed and dated written informed consent is required prior to a subject’s participation in the study 200721 (ZINN) and the performance of any protocol specific procedures. At sites where enrollment of adolescents is allowed, 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 Note: Prescreening alone does not necessarily require consent as this activity may be accomplished in the absence of study specific procedures or assessments. In many cases, standard care and standard medical triage will provide sufficient information or evidence as to whether or not the subject is eligible for the study 2.Females aged 12 to 45 years, with an uncomplicated, singleton pregnancy and intact membranes in spontaneous preterm labor (Note: This protocol includes pregnant adolescents, aged 12 to 17 years, as appropriate, unless national or local regulations restrict the age for study enrollment to subjects aged 18 to 45 years). 3.Gestational age between 240/7 and 336/7 weeks as determined by (1) known fertilization date, either in vitro fertilization or intrauterine insemination, or (2) a best estimated due date confirmed or established by by the earliest ultrasound prior to 240/7 weeks' gestation. In situations where prenatal ultrasound records are not available at the time the subject presents, the investigator may enroll the subject using the GA based on a verbal history from the subject with the intent of getting confirmation from the medical records or from the subject's primary care obstetrician as soon as possible 4.Females must be diagnosed with preterm labor according to both of the following (a or b): a.Regular uterine contractions , confirmed by tocodynamometry, at a rate of =4 contractions of at least 30 seconds duration during a 30- minute interval. Where tocodynamometry is not technically feasible, assessment by manual palpation will be permitted and must be documented AND at least 1 of the following: i.Cervical dilation =2 cm and =4 cm by digital cervical examination OR ii.If =65 years) no F.1.3.1 Number of subjects
Exclusion criteria
Exclusion criteria: 1.Fever with a temperature greater than 100.4°F (38°C) for more than 1 hour or =101°F (38.3°C) in the 24 hours prior to the start of study treatment 2.Women with maternal-fetal conditions that potentially necessitate the need for delivery, such as pre-eclampsia or fetal compromise 3.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) 4.Preterm premature rupture of membranes 5.Women with any confirmed or suspected contraindication to prolongation of pregnancy, such as placental abruption, chorioamnionitis, or placenta previa 6.Evidence of polyhydramnios (amniotic fluid index [AFI] >25 cm) or oligohydramnios (AFI 8% at any time during pregnancy), known or suspected maternal Zika infection during gestation (see SPM for details), 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) 8.Women with a history of substance abuse during the pregnancy or dependency that may have the potential to complicate the pregnancy outcome 9.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 10.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) 11.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 GSK/PPD medical monitor,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the superiority of retosiban to prolong pregnancy compared with atosiban;Secondary Objective: To describe the outcomes of newborns during the neonatal period (through 28 days post estimated date of delivery [EDD]) for retosiban compared with atosiban To describe the maternal, fetal, and neonatal safety profile during and after IV retosiban treatment compared with atosiban treatment To determine the effect of retosiban treatment compared with atosiban on health care resource use and patient-reported outcomes associated with the maternal and neonatal hospitalization To obtain further data on the pharmacokinetics of retosiban in pregnant women, including the effect of covariates such as age, weight, race/ethnicity, and GA on retosiban clearance and volume of distribution ;Primary end point(s): The primary efficacy endpoint is time to delivery from the start of IP administration until delivery,;Timepoint(s) of evaluation of this end point: 48 hours after IP infusion, then every week till delivery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The following are the key secondary efficacy endpoints: Proportion of births prior to 370/7 weeks’ gestation Proportion of births at term (370/7 to 416/7 weeks’ gestation) Length of neonatal hospital stay Proportion of neonates with any diagnosis from the neonatal morbidity and mortality composite determined up to 28 days after EDD (of 400/7 weeks) (details for each composite are provided in Section 6.2.2) Fetal or neonatal death Respiratory distress syndrome (RDS) Bronchopulmonary dysplasia Necrotizing enterocolitis or isolated perforation Sepsis Meningitis Retinopathy of prematurity Intraventricular hemorrhage (IVH) White matter injury, Cerebellar hemorrhage Clearance and volume of distribution and the effect of covariates on these parameters The following are other secondary efficacy endpoints: Proportion of neonates with any of the composite neonatal morbidity and mortality excluding RDS Proportion of neonates with each individual component of the composite neonatal morbidity and mortality endpoints Neonatal admission to a specialized care unit and length of stay Newborn hospital readmission and length of stay Ambulatory surgery Proportion of births prior to 280/7 weeks’ gestation Proportion of births prior to 320/7 weeks’ gestation Proportion of births =7 days Proportion of births =48 hours Proportion of births =24 hours The following are the safety endpoints (maternal, fetal, and neonatal, as appropriate): Incidence of reported AEs and serious AEs Significant changes in vital signs and clinical laboratory tests Incidence of treatment-limiting toxicities including both clinical and laboratory etiology causing subject to discontinue study treatment Edinburgh Postnatal Depression Scale Follow-up amniotic fluid index determined by abdominal ultrasound Fetal acidosis Neonatal Apgar scores (at 1 and 5 minutes after birth), growth parameters (weight, length, and head circumference) at birth and | — |
Countries
Belgium, Brazil, Bulgaria, Czech Republic, France, Germany, Israel, Italy, Korea, Republic of, Mexico, Philippines, Poland, Portugal, Russian Federation, Spain, Sweden, United Kingdom
Contacts
Public ContactRobert Stocken
GlaxoSmithKline Research & Development Limited
Outcome results
None listed