Obstetric Labour, Premature
Conditions
Keywords
Spontaneous Preterm Labor, retosiban, GSK221149, atosiban
Brief 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
DRUGRetosiban
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.
DRUGAtosiban
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.
DRUGPlacebo matching retosiban
A placebo infusion containing 0.9% sodium chloride (NaCl) matched for retosiban loading (bolus) dose and continuous infusion.
DRUGPlacebo matching atosiban
A placebo infusion containing 0.9% NaCl matched for the atosiban loading (bolus) dose and continuous infusion.
Sponsors
PPD Development, LP
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
12 Years to 45 Years
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Delivery From the Start of Investigational Product (IP) Administration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. Logistic regression model was used to calculate p-values. |
| Length of Neonatal Hospital Stay | 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 Participants With Births <=48 Hours From the First Study Treatment | Up to 48 hours | Number of participants who delivered in less than or equal to 48 hours from first dose of study treatment has been presented. |
| Number of Participants With Births <=24 Hours From the First Study Treatment | Up to 24 hours | Number of participants who delivered in less than or equal to 24 hours from first dose of study treatment has been presented. |
| Number of Neonates With Composite Neonatal Morbidity and Mortality | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Number of Participants With Births Prior to 35 0/7 Weeks Gestation | Up to 11 weeks | 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. |
| Number of Participants With Births <=7 Days From the First Study Treatment | Up to 7 days | Number of participants who delivered in less than or equal to 7 days from first dose of study treatment has been presented. |
| Number of Maternal Participants With Non-serious 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 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. |
| Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | Baseline and up to 1 week | 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). |
| Change From Baseline in Heart Rate in Maternal Participants | Baseline and up to 1 week | 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). |
| Change From Baseline in Respiratory Rate in Maternal Participants | Baseline and up to 1 week | 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). |
| Change From Baseline in Temperature in Maternal Participants | Baseline and up to 1 week | 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). |
| Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | 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). NA indicates standard deviation was not calculable for a single data point. |
| Change From Baseline in Erythrocytes in Maternal Participants | Baseline and up to 1 week | 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. |
| Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | 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. NA indicates standard deviation was not calculable for a single data point. |
| Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | 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). NA indicates standard deviation was not calculable for a single data point. |
| 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 | 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). NA indicates standard deviation was not calculable for a single data point. |
| Change From Baseline in Albumin and Protein Levels in Maternal Participants | 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). NA indicates standard deviation was not calculable for a single data point. |
| Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Baseline and up to 1 week | 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. |
| Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | 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). NA indicates standard deviation was not calculable for a single data point. |
| 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. |
| 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. |
| Number of Participants With Fetal Non-serious AEs and SAEs | Up to 17 weeks | 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. |
| 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. |
| 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.Only those participants with data available at the specified data points were analyzed. |
| 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. Only those participants with data available at the specified data points were analyzed. |
| Head Circumference of Neonates | Up to 17 weeks | The head circumference was determined from the neonate birth record. Only those participants with data available at the specified data points were analyzed. |
| Number of Neonatal Participants With Non-serious 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 non-serious AE and one SAE has been presented. Neonatal Safety Population consisted of neonates whose mothers received randomized treatment. |
| 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. |
| Number of Participants With Births Prior to 37 0/7 Weeks Gestation | 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. |
| Maternal Length of Stay in Hospital | Up to 28 days post EDD (40 0/7 weeks gestation) | 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). |
| 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 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. |
| 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). |
| 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). |
| 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. |
Countries
Belgium, Germany, Israel, Italy, Mexico, South Korea, Spain, Sweden, United Kingdom
Participant flow
Recruitment details
ZINN was a randomized, double-blind, double-dummy multicenter study to compare efficacy and safety of retosiban versus atosiban 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.
Pre-assignment details
From 330 planned participants 97 were randomized to receive either retosiban or atosiban intravenous (IV) infusion in a ratio of 1:1. The study was terminated early due to feasibility.
Participants by arm
| Arm | Count |
|---|---|
| Retosiban 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. | 47 |
| Atosiban Participants were administered atosiban in 3 successive stages. An initial bolus dose of 6.75 mg using atosiban 6.75 mg/0.9 milliliter (mL) solution for injection, followed by continuous high dose infusion at 18 mg/hour for 3 hours, then a lower 6 mg/hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg/5 mL concentrate for solution. | 50 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Retosiban | Atosiban | Total |
|---|---|---|---|
| Age, Continuous | 27.7 Years STANDARD_DEVIATION 6.15 | 27.1 Years STANDARD_DEVIATION 5.66 | 27.4 Years STANDARD_DEVIATION 5.88 |
| Race/Ethnicity, Customized African American/African Heritage | 0 Count of Participants | 3 Count of Participants | 3 Count of Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 7 Count of Participants | 4 Count of Participants | 11 Count of Participants |
| Race/Ethnicity, Customized Arabic/North African Heritage | 11 Count of Participants | 10 Count of Participants | 21 Count of Participants |
| Race/Ethnicity, Customized East Asian Heritage | 9 Count of Participants | 4 Count of Participants | 13 Count of Participants |
| Race/Ethnicity, Customized White/Caucasian/European Heritage | 21 Count of Participants | 31 Count of Participants | 52 Count of Participants |
| Sex: Female, Male Female | 47 Participants | 50 Participants | 97 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 50 | 0 / 47 | 0 / 50 | 0 / 46 | 1 / 50 |
| other Total, other adverse events | 34 / 47 | 25 / 50 | 6 / 47 | 6 / 50 | 23 / 46 | 17 / 50 |
| serious Total, serious adverse events | 7 / 47 | 9 / 50 | 4 / 47 | 2 / 50 | 10 / 46 | 11 / 50 |
Outcome results
Primary
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.
Time frame: Up to 17 weeks
Population: Maternal ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retosiban | Time to Delivery From the Start of Investigational Product (IP) Administration | 32.51 Days | Standard Error 2.99 |
| Atosiban | Time to Delivery From the Start of Investigational Product (IP) Administration | 33.71 Days | Standard Error 2.531 |
p-value: 0.379795% CI: [-8.879, 6.479]Finite mixture model
Secondary
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.
Time frame: Baseline and up to 1 week
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | Change From Baseline in Albumin and Protein Levels in Maternal Participants | Albumin; Day 2, n=35, 35 | -1.9 grams per liter (g/L) | Standard Deviation 2.28 |
| Retosiban | Change From Baseline in Albumin and Protein Levels in Maternal Participants | Albumin; Post-infusion assessment, n=30, 35 | 0.3 grams per liter (g/L) | Standard Deviation 2.39 |
| Retosiban | Change From Baseline in Albumin and Protein Levels in Maternal Participants | Albumin; early withdrawal, n=1, 1 | -4.0 grams per liter (g/L) | — |
| Retosiban | Change From Baseline in Albumin and Protein Levels in Maternal Participants | Protein; Day 2, n=35, 35 | -3.7 grams per liter (g/L) | Standard Deviation 4.18 |
| Retosiban | Change From Baseline in Albumin and Protein Levels in Maternal Participants | Protein; Post-infusion assessment, n=30, 35 | 0.5 grams per liter (g/L) | Standard Deviation 4.73 |
| Retosiban | Change From Baseline in Albumin and Protein Levels in Maternal Participants | Protein; early withdrawal, n=1, 1 | -5.0 grams per liter (g/L) | — |
| Atosiban | Change From Baseline in Albumin and Protein Levels in Maternal Participants | Protein; Post-infusion assessment, n=30, 35 | 0.0 grams per liter (g/L) | Standard Deviation 4.05 |
| Atosiban | Change From Baseline in Albumin and Protein Levels in Maternal Participants | Albumin; Day 2, n=35, 35 | -2.0 grams per liter (g/L) | Standard Deviation 1.95 |
| Atosiban | Change From Baseline in Albumin and Protein Levels in Maternal Participants | Protein; Day 2, n=35, 35 | -3.3 grams per liter (g/L) | Standard Deviation 3.69 |
| Atosiban | Change From Baseline in Albumin and Protein Levels in Maternal Participants | Albumin; Post-infusion assessment, n=30, 35 | -0.2 grams per liter (g/L) | Standard Deviation 2.26 |
| Atosiban | Change From Baseline in Albumin and Protein Levels in Maternal Participants | Protein; early withdrawal, n=1, 1 | -12.0 grams per liter (g/L) | — |
| Atosiban | Change From Baseline in Albumin and Protein Levels in Maternal Participants | Albumin; early withdrawal, n=1, 1 | -8.0 grams per liter (g/L) | — |
Secondary
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.
Time frame: Baseline and up to 1 week
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | 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 | AST; Post-infusion assessmet, n=29, 35 | -1.3 International Units per liter (IU/L) | Standard Deviation 4.87 |
| Retosiban | 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 | ALT; early withdrawal, n= 1, 1 | -2.0 International Units per liter (IU/L) | — |
| Retosiban | 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 | ALP; Post-infusion assessment, n=30, 35 | 14.1 International Units per liter (IU/L) | Standard Deviation 39.85 |
| Retosiban | 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 | GGT; Day 2, n= 35, 35 | -0.4 International Units per liter (IU/L) | Standard Deviation 2.44 |
| Retosiban | 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 | AST; early withdrawal, n=1, 1 | -3.0 International Units per liter (IU/L) | — |
| Retosiban | 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 | GGT; Post-infusion assessment, n=30, 35 | 17.6 International Units per liter (IU/L) | Standard Deviation 79.05 |
| Retosiban | 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 | AST; Day 2, n=34, 35 | -0.9 International Units per liter (IU/L) | Standard Deviation 4.82 |
| Retosiban | 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 | GGT; eearly withdrawal, n=1, 1 | 0.0 International Units per liter (IU/L) | — |
| Retosiban | 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 | ALT; Day 2, n= 35, 35 | -0.2 International Units per liter (IU/L) | Standard Deviation 2.53 |
| Retosiban | 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 | LDH; Day 2, n=34, 35 | -9.7 International Units per liter (IU/L) | Standard Deviation 50.58 |
| Retosiban | 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 | ALP; early withdrawal, n=1, 1 | -6.0 International Units per liter (IU/L) | — |
| Retosiban | 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 | LDH; Post-infusion assessment, n=29, 35 | -2.4 International Units per liter (IU/L) | Standard Deviation 22.08 |
| Retosiban | 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 | ALT; Post-infusion assessment, n= 30, 35 | 0.0 International Units per liter (IU/L) | Standard Deviation 6.34 |
| Retosiban | 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 | LDH; early withdrawal, n=1, 1 | -18.0 International Units per liter (IU/L) | — |
| Retosiban | 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 | ALP; Day 2, n=35, 35 | -10.1 International Units per liter (IU/L) | Standard Deviation 12.12 |
| Atosiban | 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 | LDH; early withdrawal, n=1, 1 | -59.0 International Units per liter (IU/L) | — |
| Atosiban | 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 | ALP; Day 2, n=35, 35 | -12.6 International Units per liter (IU/L) | Standard Deviation 13.07 |
| Atosiban | 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 | ALP; Post-infusion assessment, n=30, 35 | 5.9 International Units per liter (IU/L) | Standard Deviation 15.87 |
| Atosiban | 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 | ALP; early withdrawal, n=1, 1 | -19.0 International Units per liter (IU/L) | — |
| Atosiban | 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 | AST; Day 2, n=34, 35 | -1.7 International Units per liter (IU/L) | Standard Deviation 3.07 |
| Atosiban | 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 | AST; Post-infusion assessmet, n=29, 35 | -1.3 International Units per liter (IU/L) | Standard Deviation 4.09 |
| Atosiban | 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 | AST; early withdrawal, n=1, 1 | 1.0 International Units per liter (IU/L) | — |
| Atosiban | 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 | ALT; Day 2, n= 35, 35 | 0.0 International Units per liter (IU/L) | Standard Deviation 2.4 |
| Atosiban | 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 | ALT; Post-infusion assessment, n= 30, 35 | 0.8 International Units per liter (IU/L) | Standard Deviation 6.19 |
| Atosiban | 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 | ALT; early withdrawal, n= 1, 1 | 5.0 International Units per liter (IU/L) | — |
| Atosiban | 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 | GGT; Day 2, n= 35, 35 | -0.9 International Units per liter (IU/L) | Standard Deviation 3.08 |
| Atosiban | 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 | GGT; Post-infusion assessment, n=30, 35 | 2.3 International Units per liter (IU/L) | Standard Deviation 4.39 |
| Atosiban | 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 | GGT; eearly withdrawal, n=1, 1 | 0.0 International Units per liter (IU/L) | — |
| Atosiban | 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 | LDH; Day 2, n=34, 35 | -20.0 International Units per liter (IU/L) | Standard Deviation 29.18 |
| Atosiban | 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 | LDH; Post-infusion assessment, n=29, 35 | -5.4 International Units per liter (IU/L) | Standard Deviation 30.93 |
Secondary
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.
Time frame: Baseline and up to 1 week
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Basophils;Day2,n=21,23 | 0.003 Billion cells per liter (L) | Standard Deviation 0.0362 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Basophils;Post-infusion assessment,n=24,28 | 0.001 Billion cells per liter (L) | Standard Deviation 0.0315 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Basophils;early withdrawal,n=1,1 | -0.020 Billion cells per liter (L) | — |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Eosinophils;Day2,n=21,23 | -0.010 Billion cells per liter (L) | Standard Deviation 0.0626 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Eosinophils;Post-infusion assessment,n=24,28 | 0.023 Billion cells per liter (L) | Standard Deviation 0.0442 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Eosinophils;early withdrawal,n=1,1 | 0.030 Billion cells per liter (L) | — |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Lymphocytes;Day2,n=21,23 | 0.186 Billion cells per liter (L) | Standard Deviation 0.9115 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Lymphocytes;Post-infusion assessment,n=24,28 | 0.348 Billion cells per liter (L) | Standard Deviation 0.8611 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Lymphocytes;early withdrawal,n=1,1 | 0.270 Billion cells per liter (L) | — |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Monocytes;Day2,n=21,23 | 0.082 Billion cells per liter (L) | Standard Deviation 0.2222 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Monocytes;Post-infusion assessment,n=24,28 | 0.222 Billion cells per liter (L) | Standard Deviation 0.1904 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Monocytes;early withdrawal,n=1,1 | -0.160 Billion cells per liter (L) | — |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Neutrophils;Day2,n=21,23 | 0.102 Billion cells per liter (L) | Standard Deviation 2.6712 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Neutrophils;Post-infusion assessment,n=24,28 | -1.865 Billion cells per liter (L) | Standard Deviation 2.9246 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Neutrophils;early withdrawal,n=1,1 | -0.710 Billion cells per liter (L) | — |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Platelets;Day2,n=22,25 | 0.0 Billion cells per liter (L) | Standard Deviation 25.95 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Platelets;Post-infusion assessment,n=24,31 | 21.5 Billion cells per liter (L) | Standard Deviation 63.14 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Platelets;early withdrawal,n=1,1 | -33.0 Billion cells per liter (L) | — |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Leukocytes;Day2,n=23,25 | 0.17 Billion cells per liter (L) | Standard Deviation 2.785 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Leukocytes;Post-infusion assessment,n=25,30 | -1.18 Billion cells per liter (L) | Standard Deviation 2.492 |
| Retosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Leukocytes;early withdrawal,n=1,1 | -0.60 Billion cells per liter (L) | — |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Monocytes;Post-infusion assessment,n=24,28 | 0.133 Billion cells per liter (L) | Standard Deviation 0.3467 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Basophils;Day2,n=21,23 | 0.010 Billion cells per liter (L) | Standard Deviation 0.0304 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Leukocytes;Day2,n=23,25 | 0.72 Billion cells per liter (L) | Standard Deviation 2.905 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Basophils;Post-infusion assessment,n=24,28 | 0.007 Billion cells per liter (L) | Standard Deviation 0.0181 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Monocytes;early withdrawal,n=1,1 | 0.410 Billion cells per liter (L) | — |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Basophils;early withdrawal,n=1,1 | 0.030 Billion cells per liter (L) | — |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Platelets;Post-infusion assessment,n=24,31 | 20.6 Billion cells per liter (L) | Standard Deviation 43.74 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Eosinophils;Day2,n=21,23 | -0.037 Billion cells per liter (L) | Standard Deviation 0.1181 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Neutrophils;Day2,n=21,23 | 0.559 Billion cells per liter (L) | Standard Deviation 3.389 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Eosinophils;Post-infusion assessment,n=24,28 | 0.066 Billion cells per liter (L) | Standard Deviation 0.1535 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Leukocytes;early withdrawal,n=1,1 | -4.80 Billion cells per liter (L) | — |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Eosinophils;early withdrawal,n=1,1 | 0.050 Billion cells per liter (L) | — |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Neutrophils;Post-infusion assessment,n=24,28 | -0.670 Billion cells per liter (L) | Standard Deviation 2.7063 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Lymphocytes;Day2,n=21,23 | 0.067 Billion cells per liter (L) | Standard Deviation 0.6017 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Platelets;early withdrawal,n=1,1 | -58.0 Billion cells per liter (L) | — |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Lymphocytes;Post-infusion assessment,n=24,28 | 0.233 Billion cells per liter (L) | Standard Deviation 0.8047 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Neutrophils;early withdrawal,n=1,1 | -3.550 Billion cells per liter (L) | — |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Lymphocytes;early withdrawal,n=1,1 | -1.770 Billion cells per liter (L) | — |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Leukocytes;Post-infusion assessment,n=25,30 | -0.05 Billion cells per liter (L) | Standard Deviation 2.756 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Monocytes;Day2,n=21,23 | 0.044 Billion cells per liter (L) | Standard Deviation 0.2702 |
| Atosiban | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants | Platelets;Day2,n=22,25 | -2.4 Billion cells per liter (L) | Standard Deviation 36.59 |
Secondary
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.
Time frame: Baseline and up to 1 week
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Sodium; Post-infusion assessment, n= 30,35 | -1.1 millimoles per liter (mmol/L) | Standard Deviation 2.05 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Magnesium; early withdrawal, n= 1,1 | -0.060 millimoles per liter (mmol/L) | — |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Phosphate; Day 2, n= 35,35 | -0.101 millimoles per liter (mmol/L) | Standard Deviation 0.2684 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Phosphate; Post-infusion assessment, n= 30,35 | 0.041 millimoles per liter (mmol/L) | Standard Deviation 0.2267 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Phosphate; early withdrawal, n= 1,1 | 0.100 millimoles per liter (mmol/L) | — |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Sodium; Day 2, n= 35,35 | 0.7 millimoles per liter (mmol/L) | Standard Deviation 2.13 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Magnesium, Post-infusion assessment, n= 30,35 | 0.026 millimoles per liter (mmol/L) | Standard Deviation 0.076 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Sodium; early withdrawal, n= 1,1 | -1.0 millimoles per liter (mmol/L) | — |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Calcium; Day 2, n=34, 35 | -0.097 millimoles per liter (mmol/L) | Standard Deviation 0.1125 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Calcium; Post-infusion assessment, n=29, 35 | 0.018 millimoles per liter (mmol/L) | Standard Deviation 0.0953 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Calcium; early withdrawal, n=1, 1 | -0.120 millimoles per liter (mmol/L) | — |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Chloride; Day 2, n=35, 35 | 1.5 millimoles per liter (mmol/L) | Standard Deviation 2.02 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Chloride; Post-infusion assessment, n=30, 35 | -1.5 millimoles per liter (mmol/L) | Standard Deviation 1.83 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Chloride; early withdrawal, n=1, 1 | 2.0 millimoles per liter (mmol/L) | — |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Carbon dioxide; Day 2, n=34, 35 | 0.7 millimoles per liter (mmol/L) | Standard Deviation 2.34 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Carbon dioxide, Post-infusion assessment, n=29,35 | 1.9 millimoles per liter (mmol/L) | Standard Deviation 2.06 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Carbon dioxide, early withdrawal, n=1, 1 | -2.0 millimoles per liter (mmol/L) | — |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Glucose; Day 2, n=35,35 | 0.13 millimoles per liter (mmol/L) | Standard Deviation 2.013 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Glucose; Post-infusion assessment, n=30, 35 | -0.70 millimoles per liter (mmol/L) | Standard Deviation 1.994 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Glucose; early withdrawal, n= 1, 1 | 0.70 millimoles per liter (mmol/L) | — |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Potassium; Day 2, n= 34, 35 | 0.06 millimoles per liter (mmol/L) | Standard Deviation 0.392 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Potassium; Post-infusion assessment, n= 29, 35 | 0.21 millimoles per liter (mmol/L) | Standard Deviation 0.362 |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Potassium; early withdrawal, n= 1,1 | -0.10 millimoles per liter (mmol/L) | — |
| Retosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Magnesium; Day 2, n= 35,35 | 0.073 millimoles per liter (mmol/L) | Standard Deviation 0.2098 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Potassium; early withdrawal, n= 1,1 | 0.50 millimoles per liter (mmol/L) | — |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Magnesium, Post-infusion assessment, n= 30,35 | 0.009 millimoles per liter (mmol/L) | Standard Deviation 0.0772 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Chloride; Post-infusion assessment, n=30, 35 | -1.3 millimoles per liter (mmol/L) | Standard Deviation 2.63 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Magnesium; early withdrawal, n= 1,1 | 0.030 millimoles per liter (mmol/L) | — |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Glucose; Post-infusion assessment, n=30, 35 | -0.35 millimoles per liter (mmol/L) | Standard Deviation 2.283 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Phosphate; Day 2, n= 35,35 | -0.170 millimoles per liter (mmol/L) | Standard Deviation 0.2357 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Chloride; early withdrawal, n=1, 1 | 8.0 millimoles per liter (mmol/L) | — |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Phosphate; Post-infusion assessment, n= 30,35 | 0.094 millimoles per liter (mmol/L) | Standard Deviation 0.2864 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Potassium; Post-infusion assessment, n= 29, 35 | 0.18 millimoles per liter (mmol/L) | Standard Deviation 0.355 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Phosphate; early withdrawal, n= 1,1 | -0.120 millimoles per liter (mmol/L) | — |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Carbon dioxide; Day 2, n=34, 35 | 0.3 millimoles per liter (mmol/L) | Standard Deviation 2.63 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Sodium; Day 2, n= 35,35 | 0.1 millimoles per liter (mmol/L) | Standard Deviation 1.69 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Glucose; early withdrawal, n= 1, 1 | -5.20 millimoles per liter (mmol/L) | — |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Sodium; Post-infusion assessment, n= 30,35 | -0.2 millimoles per liter (mmol/L) | Standard Deviation 2.11 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Carbon dioxide, Post-infusion assessment, n=29,35 | 1.9 millimoles per liter (mmol/L) | Standard Deviation 2.67 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Sodium; early withdrawal, n= 1,1 | 3.0 millimoles per liter (mmol/L) | — |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Magnesium; Day 2, n= 35,35 | -0.003 millimoles per liter (mmol/L) | Standard Deviation 0.0657 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Calcium; Day 2, n=34, 35 | -0.078 millimoles per liter (mmol/L) | Standard Deviation 0.0884 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Carbon dioxide, early withdrawal, n=1, 1 | 6.0 millimoles per liter (mmol/L) | — |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Calcium; Post-infusion assessment, n=29, 35 | 0.023 millimoles per liter (mmol/L) | Standard Deviation 0.0861 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Potassium; Day 2, n= 34, 35 | -0.06 millimoles per liter (mmol/L) | Standard Deviation 0.346 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Calcium; early withdrawal, n=1, 1 | -0.230 millimoles per liter (mmol/L) | — |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Glucose; Day 2, n=35,35 | 1.51 millimoles per liter (mmol/L) | Standard Deviation 2.156 |
| Atosiban | Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants | Chloride; Day 2, n=35, 35 | 1.4 millimoles per liter (mmol/L) | Standard Deviation 2.03 |
Secondary
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).
Time frame: Baseline and up to 1 week
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | DBP; Day 1: 15 to 30 minutes, n=42,45 | -3.6 Millimeter of mercury (mmHg) | Standard Deviation 10.96 |
| Retosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | DBP; Day 1: 4 to 8 hours, n=42,43 | -4.3 Millimeter of mercury (mmHg) | Standard Deviation 11.07 |
| Retosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | DBP; Day 1: 20 to 24 hours, n=38,41 | -5.7 Millimeter of mercury (mmHg) | Standard Deviation 9.31 |
| Retosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | DBP; Day 2, n=40,42 | -4.4 Millimeter of mercury (mmHg) | Standard Deviation 9.57 |
| Retosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | DBP; Post-infusion assessment, n=35,41 | -1.6 Millimeter of mercury (mmHg) | Standard Deviation 8.63 |
| Retosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | SBP; Day 1: 15 to 30 minutes, n=42,45 | -2.5 Millimeter of mercury (mmHg) | Standard Deviation 9.53 |
| Retosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | SBP; Day 1: 4 to 8 hours, n=42,43 | -4.3 Millimeter of mercury (mmHg) | Standard Deviation 9.05 |
| Retosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | SBP; Day 1: 20 to 24 hours, n=38,41 | -4.1 Millimeter of mercury (mmHg) | Standard Deviation 10.16 |
| Retosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | SBP; Day 2, n=40,42 | -3.9 Millimeter of mercury (mmHg) | Standard Deviation 11.53 |
| Retosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | SBP; Post-infusion assessment, n=35,41 | -1.5 Millimeter of mercury (mmHg) | Standard Deviation 11.04 |
| Atosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | SBP; Day 1: 20 to 24 hours, n=38,41 | -5.2 Millimeter of mercury (mmHg) | Standard Deviation 13.03 |
| Atosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | DBP; Day 1: 15 to 30 minutes, n=42,45 | -0.7 Millimeter of mercury (mmHg) | Standard Deviation 8.95 |
| Atosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | SBP; Day 1: 15 to 30 minutes, n=42,45 | -0.4 Millimeter of mercury (mmHg) | Standard Deviation 11.02 |
| Atosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | DBP; Day 1: 4 to 8 hours, n=42,43 | -3.7 Millimeter of mercury (mmHg) | Standard Deviation 10.28 |
| Atosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | SBP; Post-infusion assessment, n=35,41 | -2.1 Millimeter of mercury (mmHg) | Standard Deviation 11.37 |
| Atosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | DBP; Day 1: 20 to 24 hours, n=38,41 | -4.1 Millimeter of mercury (mmHg) | Standard Deviation 9.9 |
| Atosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | SBP; Day 1: 4 to 8 hours, n=42,43 | -3.3 Millimeter of mercury (mmHg) | Standard Deviation 12.21 |
| Atosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | DBP; Day 2, n=40,42 | -2.6 Millimeter of mercury (mmHg) | Standard Deviation 9.93 |
| Atosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | SBP; Day 2, n=40,42 | -3.0 Millimeter of mercury (mmHg) | Standard Deviation 11.35 |
| Atosiban | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants | DBP; Post-infusion assessment, n=35,41 | 1.3 Millimeter of mercury (mmHg) | Standard Deviation 10.12 |
Secondary
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.
Time frame: Baseline and up to 1 week
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Direct Bilirubin; Day2, n=35,35 | -0.3 micromoles per liter (µmol/L) | Standard Deviation 0.85 |
| Retosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Post-infusion assessment, n=30,35 | -0.5 micromoles per liter (µmol/L) | Standard Deviation 3.41 |
| Retosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Direct Bilirubin;early withdrawal, n=1,1 | 0.0 micromoles per liter (µmol/L) | — |
| Retosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Bilirubin;Day2, n= 35,35 | -0.7 micromoles per liter (µmol/L) | Standard Deviation 2.52 |
| Retosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Bilirubin; Post-infusion assessment, n= 30, 35 | -1.1 micromoles per liter (µmol/L) | Standard Deviation 8.24 |
| Retosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Bilirubin; early withdrawal, n= 1,1 | -2.0 micromoles per liter (µmol/L) | — |
| Retosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Indirect Bilirubin; Day2, n=35,35 | -0.4 micromoles per liter (µmol/L) | Standard Deviation 2.35 |
| Retosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Indirect Bilirubin;Postinfusion assessment,n=30,35 | -0.6 micromoles per liter (µmol/L) | Standard Deviation 5.06 |
| Retosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Indirect Bilirubin; early withdrawal, n=1,1 | -2.0 micromoles per liter (µmol/L) | — |
| Retosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Creatinine; Day2, n=35,34 | 1.75 micromoles per liter (µmol/L) | Standard Deviation 6.765 |
| Retosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Creatinine; Post-infusion assessment, n=30,33 | 2.19 micromoles per liter (µmol/L) | Standard Deviation 4.437 |
| Retosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Creatinine; early withdrawal, n=1,1 | -0.90 micromoles per liter (µmol/L) | — |
| Atosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Creatinine; Post-infusion assessment, n=30,33 | 0.72 micromoles per liter (µmol/L) | Standard Deviation 4.68 |
| Atosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Direct Bilirubin; Day2, n=35,35 | -0.3 micromoles per liter (µmol/L) | Standard Deviation 0.66 |
| Atosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Indirect Bilirubin; Day2, n=35,35 | -1.1 micromoles per liter (µmol/L) | Standard Deviation 1.98 |
| Atosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Post-infusion assessment, n=30,35 | -0.1 micromoles per liter (µmol/L) | Standard Deviation 0.73 |
| Atosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Creatinine; Day2, n=35,34 | 0.04 micromoles per liter (µmol/L) | Standard Deviation 5.336 |
| Atosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Direct Bilirubin;early withdrawal, n=1,1 | 0.0 micromoles per liter (µmol/L) | — |
| Atosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Indirect Bilirubin;Postinfusion assessment,n=30,35 | -0.4 micromoles per liter (µmol/L) | Standard Deviation 2.03 |
| Atosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Bilirubin;Day2, n= 35,35 | -1.3 micromoles per liter (µmol/L) | Standard Deviation 2.03 |
| Atosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Creatinine; early withdrawal, n=1,1 | -6.10 micromoles per liter (µmol/L) | — |
| Atosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Bilirubin; Post-infusion assessment, n= 30, 35 | -0.5 micromoles per liter (µmol/L) | Standard Deviation 2.01 |
| Atosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Indirect Bilirubin; early withdrawal, n=1,1 | -3.0 micromoles per liter (µmol/L) | — |
| Atosiban | Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants | Bilirubin; early withdrawal, n= 1,1 | -3.0 micromoles per liter (µmol/L) | — |
Secondary
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.
Time frame: Baseline and up to 1 week
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | MCV; Day 2, n=23, 27 | 0.3 femtoliter (fL) | Standard Deviation 2.67 |
| Retosiban | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | MCV; Post-infusion assessment, n=25, 31 | -1.2 femtoliter (fL) | Standard Deviation 2.17 |
| Retosiban | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | MCV; early withdrawal, n=1, 1 | -1.0 femtoliter (fL) | — |
| Retosiban | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | MPV; Day 2, n=22, 25 | 0.05 femtoliter (fL) | Standard Deviation 0.607 |
| Retosiban | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | MPV, Post-infusion assessment, n=24, 31 | -0.10 femtoliter (fL) | Standard Deviation 0.639 |
| Retosiban | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | MPV, early withdrawal, n=1, 1 | 0.00 femtoliter (fL) | — |
| Atosiban | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | MPV, Post-infusion assessment, n=24, 31 | -0.03 femtoliter (fL) | Standard Deviation 0.803 |
| Atosiban | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | MCV; Day 2, n=23, 27 | -0.4 femtoliter (fL) | Standard Deviation 1.82 |
| Atosiban | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | MPV; Day 2, n=22, 25 | 0.06 femtoliter (fL) | Standard Deviation 0.553 |
| Atosiban | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | MCV; Post-infusion assessment, n=25, 31 | -1.0 femtoliter (fL) | Standard Deviation 2.22 |
| Atosiban | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | MPV, early withdrawal, n=1, 1 | -1.40 femtoliter (fL) | — |
| Atosiban | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants | MCV; early withdrawal, n=1, 1 | -5.0 femtoliter (fL) | — |
Secondary
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.
Time frame: Baseline and up to 1 week
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | Change From Baseline in Erythrocytes in Maternal Participants | Day 2, n=23, 27 | -0.22 Trillion cells per liter | Standard Deviation 0.284 |
| Retosiban | Change From Baseline in Erythrocytes in Maternal Participants | Post-infusion assessment, n=25, 31 | 0.06 Trillion cells per liter | Standard Deviation 0.257 |
| Retosiban | Change From Baseline in Erythrocytes in Maternal Participants | Early withdrawal, n =1, 1 | -0.20 Trillion cells per liter | — |
| Atosiban | Change From Baseline in Erythrocytes in Maternal Participants | Day 2, n=23, 27 | -0.29 Trillion cells per liter | Standard Deviation 0.261 |
| Atosiban | Change From Baseline in Erythrocytes in Maternal Participants | Post-infusion assessment, n=25, 31 | 0.05 Trillion cells per liter | Standard Deviation 0.236 |
| Atosiban | Change From Baseline in Erythrocytes in Maternal Participants | Early withdrawal, n =1, 1 | -0.70 Trillion cells per liter | — |
Secondary
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).
Time frame: Baseline and up to 1 week
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | Change From Baseline in Heart Rate in Maternal Participants | Day 1: 4 to 8 hours, n=42, 43 | -5.0 Beats per minute | Standard Deviation 13.69 |
| Retosiban | Change From Baseline in Heart Rate in Maternal Participants | Day 2, n=39, 41 | -2.2 Beats per minute | Standard Deviation 11.81 |
| Retosiban | Change From Baseline in Heart Rate in Maternal Participants | Day 1: 20 to 24 hours, n=38, 41 | -1.2 Beats per minute | Standard Deviation 14.44 |
| Retosiban | Change From Baseline in Heart Rate in Maternal Participants | Post-infusion assessment, n=35, 41 | -2.7 Beats per minute | Standard Deviation 12.9 |
| Retosiban | Change From Baseline in Heart Rate in Maternal Participants | Day 1: 15 to 30 minutes, n=42,46 | -3.0 Beats per minute | Standard Deviation 12.65 |
| Atosiban | Change From Baseline in Heart Rate in Maternal Participants | Post-infusion assessment, n=35, 41 | -1.8 Beats per minute | Standard Deviation 13.83 |
| Atosiban | Change From Baseline in Heart Rate in Maternal Participants | Day 1: 15 to 30 minutes, n=42,46 | -0.8 Beats per minute | Standard Deviation 10.45 |
| Atosiban | Change From Baseline in Heart Rate in Maternal Participants | Day 1: 4 to 8 hours, n=42, 43 | -3.0 Beats per minute | Standard Deviation 13.65 |
| Atosiban | Change From Baseline in Heart Rate in Maternal Participants | Day 1: 20 to 24 hours, n=38, 41 | -3.1 Beats per minute | Standard Deviation 13.82 |
| Atosiban | Change From Baseline in Heart Rate in Maternal Participants | Day 2, n=39, 41 | -2.3 Beats per minute | Standard Deviation 13.44 |
Secondary
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.
Time frame: Baseline and up to 1 week
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | Hemoglobin; Day2, n=23, 27 | -5.4 grams per liter (g/L) | Standard Deviation 7.81 |
| Retosiban | Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | Hemoglobin; Post-infusion assessment, n=25, 31 | 0.8 grams per liter (g/L) | Standard Deviation 7.55 |
| Retosiban | Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | Hemoglobin; early withdrawal, n=1, 1 | -8.0 grams per liter (g/L) | — |
| Retosiban | Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | MCHC; Day 2, n=23, 27 | 1.0 grams per liter (g/L) | Standard Deviation 9.41 |
| Retosiban | Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | MCHC; Post-infusion assessment, n=25, 31 | 1.0 grams per liter (g/L) | Standard Deviation 7.36 |
| Retosiban | Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | MCHC; early withdrawal, n=1, 1 | -3.0 grams per liter (g/L) | — |
| Atosiban | Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | MCHC; Post-infusion assessment, n=25, 31 | 0.4 grams per liter (g/L) | Standard Deviation 8.98 |
| Atosiban | Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | Hemoglobin; Day2, n=23, 27 | -8.4 grams per liter (g/L) | Standard Deviation 6.86 |
| Atosiban | Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | MCHC; Day 2, n=23, 27 | 0.9 grams per liter (g/L) | Standard Deviation 6.85 |
| Atosiban | Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | Hemoglobin; Post-infusion assessment, n=25, 31 | 0.5 grams per liter (g/L) | Standard Deviation 5.37 |
| Atosiban | Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | MCHC; early withdrawal, n=1, 1 | 24.0 grams per liter (g/L) | — |
| Atosiban | Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants | Hemoglobin; early withdrawal, n=1, 1 | -19.0 grams per liter (g/L) | — |
Secondary
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).
Time frame: Baseline and up to 1 week
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | Change From Baseline in Respiratory Rate in Maternal Participants | Day 1: 4 to 8 hours, n=23, 24 | 0.0 breaths per minute | Standard Deviation 1.65 |
| Retosiban | Change From Baseline in Respiratory Rate in Maternal Participants | Day 2, n=23, 24 | -0.3 breaths per minute | Standard Deviation 1.64 |
| Retosiban | Change From Baseline in Respiratory Rate in Maternal Participants | Day 1: 20 to 24 hours, n=21, 21 | 0.2 breaths per minute | Standard Deviation 1.87 |
| Retosiban | Change From Baseline in Respiratory Rate in Maternal Participants | Post-infusion assessment, n=22, 23 | -0.3 breaths per minute | Standard Deviation 2.15 |
| Retosiban | Change From Baseline in Respiratory Rate in Maternal Participants | Day 1: 15 to 30 minutes, n=25, 28 | 0.3 breaths per minute | Standard Deviation 2.82 |
| Atosiban | Change From Baseline in Respiratory Rate in Maternal Participants | Post-infusion assessment, n=22, 23 | -1.3 breaths per minute | Standard Deviation 2.7 |
| Atosiban | Change From Baseline in Respiratory Rate in Maternal Participants | Day 1: 15 to 30 minutes, n=25, 28 | -0.6 breaths per minute | Standard Deviation 1.93 |
| Atosiban | Change From Baseline in Respiratory Rate in Maternal Participants | Day 1: 4 to 8 hours, n=23, 24 | -0.8 breaths per minute | Standard Deviation 2.33 |
| Atosiban | Change From Baseline in Respiratory Rate in Maternal Participants | Day 1: 20 to 24 hours, n=21, 21 | -0.6 breaths per minute | Standard Deviation 2.4 |
| Atosiban | Change From Baseline in Respiratory Rate in Maternal Participants | Day 2, n=23, 24 | 0.2 breaths per minute | Standard Deviation 3.45 |
Secondary
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).
Time frame: Baseline and up to 1 week
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | Change From Baseline in Temperature in Maternal Participants | Day 1: 4 to 8 hours, n=40, 42 | -0.06 degree Celsius | Standard Deviation 0.359 |
| Retosiban | Change From Baseline in Temperature in Maternal Participants | Day 2, n=40, 42 | -0.07 degree Celsius | Standard Deviation 0.467 |
| Retosiban | Change From Baseline in Temperature in Maternal Participants | Day 1: 20 to 24 hours, n=37, 41 | -0.07 degree Celsius | Standard Deviation 0.366 |
| Retosiban | Change From Baseline in Temperature in Maternal Participants | Post-infusion assessment, n=35, 41 | -0.18 degree Celsius | Standard Deviation 0.334 |
| Retosiban | Change From Baseline in Temperature in Maternal Participants | Day 1: 15 to 30 minutes, n=41, 43 | -0.02 degree Celsius | Standard Deviation 0.379 |
| Atosiban | Change From Baseline in Temperature in Maternal Participants | Post-infusion assessment, n=35, 41 | -0.20 degree Celsius | Standard Deviation 0.422 |
| Atosiban | Change From Baseline in Temperature in Maternal Participants | Day 1: 15 to 30 minutes, n=41, 43 | 0.02 degree Celsius | Standard Deviation 0.467 |
| Atosiban | Change From Baseline in Temperature in Maternal Participants | Day 1: 4 to 8 hours, n=40, 42 | 0.00 degree Celsius | Standard Deviation 0.507 |
| Atosiban | Change From Baseline in Temperature in Maternal Participants | Day 1: 20 to 24 hours, n=37, 41 | -0.03 degree Celsius | Standard Deviation 0.486 |
| Atosiban | Change From Baseline in Temperature in Maternal Participants | Day 2, n=40, 42 | -0.06 degree Celsius | Standard Deviation 0.353 |
Secondary
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.
Time frame: Up to 17 weeks
Population: Neonatal ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retosiban | Head Circumference of Neonates | 32.95 centimeters (cm) | Standard Deviation 2.179 |
| Atosiban | Head Circumference of Neonates | 33.00 centimeters (cm) | Standard Deviation 1.892 |
Secondary
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.
Time frame: Up to 28 days post estimated date of delivery (EDD) of 40 0/7 weeks gestation
Population: Neonatal ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Retosiban | Length of Neonatal Hospital Stay | 4.98 Days |
| Atosiban | Length of Neonatal Hospital Stay | 4.38 Days |
p-value: 0.567295% CI: [0.73, 1.76]ANCOVA
Secondary
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.
Time frame: Up to 28 days post EDD (40 0/7 weeks gestation)
Population: Neonatal Safety Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Retosiban | Length of Stay in Specialized Care Unit | 13.65 Days |
| Atosiban | Length of Stay in Specialized Care Unit | 12.49 Days |
Secondary
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).
Time frame: Up to 28 days post EDD (40 0/7 weeks gestation)
Population: Maternal Safety Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Retosiban | Maternal Length of Stay in Hospital | Preterm labor, n=13, 10 | 5.549 Days |
| Retosiban | Maternal Length of Stay in Hospital | Term labor, n=25, 28 | 3.146 Days |
| Atosiban | Maternal Length of Stay in Hospital | Preterm labor, n=13, 10 | 7.487 Days |
| Atosiban | Maternal Length of Stay in Hospital | Term labor, n=25, 28 | 3.398 Days |
Secondary
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.
Time frame: Up to 5 minutes after birth
Population: Neonatal ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retosiban | Neonatal APGAR Scores | one minute, n=46, 50 | 8.2 Score on APGAR scale | Standard Deviation 1.35 |
| Retosiban | Neonatal APGAR Scores | five minutes, n=46, 50 | 9.1 Score on APGAR scale | Standard Deviation 0.96 |
| Atosiban | Neonatal APGAR Scores | one minute, n=46, 50 | 8.4 Score on APGAR scale | Standard Deviation 1.14 |
| Atosiban | Neonatal APGAR Scores | five minutes, n=46, 50 | 9.4 Score on APGAR scale | Standard Deviation 0.67 |
Secondary
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.
Time frame: Up to 6 weeks post-delivery
Population: Maternal Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Maternal Participants With AEs of Special Interest (AESI) | 4 Participants |
| Atosiban | Number of Maternal Participants With AEs of Special Interest (AESI) | 7 Participants |
Secondary
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.
Time frame: Up to 6 weeks post-delivery
Population: Maternal Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Maternal Participants With Disease Related AEs (DRE) | 5 Participants |
| Atosiban | Number of Maternal Participants With Disease Related AEs (DRE) | 5 Participants |
Secondary
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.
Time frame: Up to 6 weeks after delivery
Population: Maternal Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retosiban | Number of Maternal Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) | Non-serious AE | 34 Participants |
| Retosiban | Number of Maternal Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 7 Participants |
| Atosiban | Number of Maternal Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) | Non-serious AE | 25 Participants |
| Atosiban | Number of Maternal Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 9 Participants |
Secondary
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.
Time frame: Up to 28 days after EDD of 40 weeks gestation
Population: Neonatal Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Neonatal Participants With AESI | 19 Participants |
| Atosiban | Number of Neonatal Participants With AESI | 16 Participants |
Secondary
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.
Time frame: Up to 28 days after EDD of 40 weeks gestation
Population: Neonatal Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Neonatal Participants With DRE | 5 Participants |
| Atosiban | Number of Neonatal Participants With DRE | 3 Participants |
Secondary
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.
Time frame: Up to 28 days after the EDD of 40 weeks gestation
Population: Neonatal Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retosiban | Number of Neonatal Participants With Non-serious AEs and SAEs | Non-serious AEs | 23 Participants |
| Retosiban | Number of Neonatal Participants With Non-serious AEs and SAEs | SAEs | 10 Participants |
| Atosiban | Number of Neonatal Participants With Non-serious AEs and SAEs | Non-serious AEs | 17 Participants |
| Atosiban | Number of Neonatal Participants With Non-serious AEs and SAEs | SAEs | 11 Participants |
Secondary
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.
Time frame: Up to 28 weeks after EDD (40 weeks gestation)
Population: Neonatal ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Neonates With Any Composite Neonatal Morbidity and Mortality, Excluding RDS | 0 Participants |
| Atosiban | Number of Neonates With Any Composite Neonatal Morbidity and Mortality, Excluding RDS | 1 Participants |
Secondary
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.
Time frame: Up to 28 weeks after EDD (40 weeks gestation)
Population: Neonatal ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Neonates With Composite Neonatal Morbidity and Mortality | 3 Participants |
| Atosiban | Number of Neonates With Composite Neonatal Morbidity and Mortality | 2 Participants |
p-value: 0.506695% CI: [0.3, 11.71]Regression, Logistic
Secondary
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.
Time frame: Up to 28 weeks after EDD (40 weeks gestation)
Population: Neonatal ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | RDS | 3 Participants |
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | ROP | 0 Participants |
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | NEC or isolated perforation | 0 Participants |
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | IVH | 0 Participants |
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Neonatal death | 0 Participants |
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | PVL | 0 Participants |
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Sepsis | 0 Participants |
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Porencephalic Cyst | 0 Participants |
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | BPD | 0 Participants |
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Persistent Ventriculomegaly | 0 Participants |
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Meningitis | 0 Participants |
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Cerebellar Hemorrhage | 0 Participants |
| Retosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Fetal death | 0 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Cerebellar Hemorrhage | 0 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Fetal death | 0 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Neonatal death | 1 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | RDS | 1 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | BPD | 0 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | NEC or isolated perforation | 0 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Sepsis | 0 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Meningitis | 0 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | ROP | 0 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | IVH | 0 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | PVL | 0 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Porencephalic Cyst | 0 Participants |
| Atosiban | Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality | Persistent Ventriculomegaly | 0 Participants |
Secondary
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.
Time frame: Up to 28 days of EDD (40 0/7 weeks gestation)
Population: Neonatal Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Newborn Participants With Hospital Readmission | 2 Participants |
| Atosiban | Number of Newborn Participants With Hospital Readmission | 3 Participants |
Secondary
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.
Time frame: Up to 28 days post EDD (40 0/7 weeks gestation)
Population: Maternal Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retosiban | Number of Participants Admitted to Particular Hospital Unit | Preterm labor, general ward | 9 Participants |
| Retosiban | Number of Participants Admitted to Particular Hospital Unit | Preterm labor, private/semi-private room | 1 Participants |
| Retosiban | Number of Participants Admitted to Particular Hospital Unit | Preterm, Other | 3 Participants |
| Retosiban | Number of Participants Admitted to Particular Hospital Unit | Normal term labor, general ward | 16 Participants |
| Retosiban | Number of Participants Admitted to Particular Hospital Unit | Normal term labor, ward-not specified | 2 Participants |
| Retosiban | Number of Participants Admitted to Particular Hospital Unit | Normal term labor,private/semi-private room | 1 Participants |
| Retosiban | Number of Participants Admitted to Particular Hospital Unit | Normal term labor, recovery | 1 Participants |
| Retosiban | Number of Participants Admitted to Particular Hospital Unit | Normal term labor, Other | 5 Participants |
| Atosiban | Number of Participants Admitted to Particular Hospital Unit | Normal term labor, Other | 7 Participants |
| Atosiban | Number of Participants Admitted to Particular Hospital Unit | Preterm labor, general ward | 7 Participants |
| Atosiban | Number of Participants Admitted to Particular Hospital Unit | Normal term labor, ward-not specified | 0 Participants |
| Atosiban | Number of Participants Admitted to Particular Hospital Unit | Preterm labor, private/semi-private room | 0 Participants |
| Atosiban | Number of Participants Admitted to Particular Hospital Unit | Normal term labor, recovery | 2 Participants |
| Atosiban | Number of Participants Admitted to Particular Hospital Unit | Preterm, Other | 4 Participants |
| Atosiban | Number of Participants Admitted to Particular Hospital Unit | Normal term labor,private/semi-private room | 7 Participants |
| Atosiban | Number of Participants Admitted to Particular Hospital Unit | Normal term labor, general ward | 12 Participants |
Secondary
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.
Time frame: Up to 24 hours
Population: Maternal ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Participants With Births <=24 Hours From the First Study Treatment | 3 Participants |
| Atosiban | Number of Participants With Births <=24 Hours From the First Study Treatment | 6 Participants |
p-value: 0.468295% CI: [0.13, 2.58]Regression, Logistic
Secondary
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.
Time frame: Up to 48 hours
Population: Maternal ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Participants With Births <=48 Hours From the First Study Treatment | 6 Participants |
| Atosiban | Number of Participants With Births <=48 Hours From the First Study Treatment | 6 Participants |
p-value: 0.52595% CI: [0.43, 5.15]Regression, Logistic
Secondary
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.
Time frame: Up to 7 days
Population: Maternal ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Participants With Births <=7 Days From the First Study Treatment | 10 Participants |
| Atosiban | Number of Participants With Births <=7 Days From the First Study Treatment | 7 Participants |
p-value: 0.143295% CI: [0.75, 7.24]Regression, Logistic
Secondary
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.
Time frame: Up to 17 weeks
Population: Maternal ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Participants With Births at Term | 21 Participants |
| Atosiban | Number of Participants With Births at Term | 22 Participants |
p-value: 0.95295% CI: [0.46, 2.29]Regression, Logistic
Secondary
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.
Time frame: Up to 4 weeks
Population: Maternal ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Participants With Births Prior to 28 0/7 Weeks Gestation | 0 Participants |
| Atosiban | Number of Participants With Births Prior to 28 0/7 Weeks Gestation | 0 Participants |
Secondary
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.
Time frame: Up to 8 weeks
Population: Maternal ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Participants With Births Prior to 32 0/7 Weeks Gestation | 3 Participants |
| Atosiban | Number of Participants With Births Prior to 32 0/7 Weeks Gestation | 3 Participants |
p-value: 0.77995% CI: [0.12, 4.84]Regression, Logistic
Secondary
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.
Time frame: Up to 11 weeks
Population: Maternal ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Participants With Births Prior to 35 0/7 Weeks Gestation | 14 Participants |
| Atosiban | Number of Participants With Births Prior to 35 0/7 Weeks Gestation | 14 Participants |
p-value: 0.664695% CI: [0.51, 2.9]Regression, Logistic
Secondary
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.
Time frame: Up to 13 weeks
Population: Maternal ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Participants With Births Prior to 37 0/7 Weeks Gestation | 25 Participants |
| Atosiban | Number of Participants With Births Prior to 37 0/7 Weeks Gestation | 28 Participants |
p-value: 0.95295% CI: [0.44, 2.18]Regression, Logistic
Secondary
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.
Time frame: Up to 17 weeks
Population: Maternal Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retosiban | Number of Participants With Fetal AESI | 5 Participants |
| Atosiban | Number of Participants With Fetal AESI | 5 Participants |
Secondary
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.
Time frame: Up to 17 weeks
Population: Maternal Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retosiban | Number of Participants With Fetal Non-serious AEs and SAEs | Non-serious AE | 6 Participants |
| Retosiban | Number of Participants With Fetal Non-serious AEs and SAEs | SAE | 4 Participants |
| Atosiban | Number of Participants With Fetal Non-serious AEs and SAEs | Non-serious AE | 6 Participants |
| Atosiban | Number of Participants With Fetal Non-serious AEs and SAEs | SAE | 2 Participants |
Secondary
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).
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Retosiban | Retosiban Clearance | 83.4 Liters per hour | Geometric Coefficient of Variation 5.25 |
Secondary
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).
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Retosiban | Volume of Distribution of Retosiban | 68.6 Liters | Geometric Coefficient of Variation 109 |
Secondary
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.
Time frame: Up to 17 weeks
Population: Neonatal ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retosiban | Weight of Neonates | 2761.9 grams (g) | Standard Deviation 567.84 |
| Atosiban | Weight of Neonates | 2844.4 grams (g) | Standard Deviation 664.8 |