Preterm Labour MedDRA version: 19.1 Level: PT Classification code 10036600 Term: Premature labour System Organ Class: 10036585 - Pregnancy, puerperium and perinatal conditions
Conditions
Interventions
Product Name: Retosiban
Product Code: GSK221149
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Retosiban
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. 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. 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 Labour (NOTE: Since local laws, customs, and institutional practice vary globally, investigator discretion in the enrollment of pediatric subjects is permitted, expect in Italy) Italian Subjects: In Italy, the age restriction for study enrollment is 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 the earliest ultrasound performed before 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 criteria (a and 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 b. At least 1 of the following: i. Cervical dilation =2 cm and =4 cm by digital cervical examination OR ii. If <2 cm dilation by the required initial digital cervical examination, a cervical change (2 examinations must be documented) consistent with 1 of the following: -An absolute increase of at least 25% effacement (e.g. a change in effacement from 50% to 75%) by digital examination or a 10-mm decrease in cervical length by transvaginal ultrasound. OR -A 1-cm increase in cervical dilation by digital cervical examination 5. Current or past tocolytic treatment as follows: a. Subje
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Fever with a temperature >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. 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) NOTES: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice, or cirrhosis Chronic stable hepatitis B and C (e.g., presence of hepatitis B surface antigen (or positive hepatitis C antibody test result at Screening or within 3 months prior to first dose of study treatment) are acceptable if subject otherwise meets entry criteria 11. History of sensitivity to any of the IPs or components thereof or a history of drug or other allergy that, in the opinion of the investigator or PPD medical monitor, contraindicates the subject’s participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the superiority of retosiban to prolong pregnancy and improve neonatal outcomes compared with placebo; Secondary Objective: To describe the maternal, fetal, and neonatal safety profile during and after intravenous (IV) retosiban treatment compared with placebo To determine the effect of retosiban treatment compared with placebo on health care resource use for the maternal and neonatal hospitalizations 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): Time to delivery or treatment failure, whichever occurs first. Time to delivery will be calculated from the start of study treatment administration until delivery. Time to treatment failure will be calculated from the start of study treatment administration to the administration of any putative tocolytic medication •Proportion of neonates with any diagnosis from the neonatal morbidity and mortality composite determined up to 28 days after the estimated date of delivery (EDD) of 400/7weeks: •Fetal or neonatal death •Respiratory distress syndrome (RDS) o Requiring continuous positive airway pressure or mechanical ventilation. Diagnosis requires a chest radiograph consistent with RDS (reticulogranular appearance to the lung fields or air bronchograms) within the first 24 hours of life, OR o Received surfactant for a clinical picture of RDS within the first 24 hours of life •Broncho pulmonary dysplasia at =36 weeks postmenstrual age (determined by adding chronological age to GA at delivery), defined asf ollows: o >21% supplemental oxygen requirement, OR o Use of high-flow nasal cannula at =1 L (21% oxygen) •Necr | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Supportive Key Secondary •Time to delivery 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 Supportive Other Secondary •Proportion of births prior to 320/7 weeks’gestation •Proportion of births prior to 280/7 weeks’gestation •Proportion of births =7 days •Proportion of births =48 hours Proportion of births =24 hours •Proportion of neonates with any of the co-primary 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 •Time to treatment failure •Proportion of women receiving any putative tocolytic •Proportion of women experiencing subsequent episodes of preterm labor Maternal: •Incidence of reported AEs and serious AEs (SAEs) •Significant changes in vital signs and clinical laboratory tests •Incidence of clinical and laboratory toxicities causing subject to discontinue study treatment •Incidence of women scoring 12 or higher on the Edinburgh Postnatal Depression Scale (EPDS) •Maternal AEs of special interest •Maternal death •Chorioamnionitis and its complications o Clinical chorioamnionitis, preterm premature rupture of membranes, endomyometritis, wound infection, pelvic abscess, bacteremia, septic shock, disseminated intra | — |
Countries
Australia, Canada, Ireland, Italy, Japan, United Kingdom, United States
Contacts
Public ContactRobert Stocken
GlaxoSmithKline Research & Development Limited
Outcome results
None listed