"Retosiban"

Safety and Outcomes in Infants Born to Mothers Participating in Retosiban Treatment Trials: ARIOS Follow-Up Study.  Retosiban, an oxytocin receptor antagonist, was developed for treating spontaneous preterm labor (sPTL) in women with intact membranes. This ARIOS follow-up study aimed to characterize clinical safety, morbidity, and mortality of infants exposed to retosiban or comparator over 2 years.  ARIOS prospectively assessed outcomes in infants whose mothers received at least one dose of retosiban or comparator (placebo/atosiban) in two Phase 3 sPTL trials. Both trials were terminated prematurely owing to poor enrolment. Infants could be enrolled into ARIOS from 28 days after estimated due date until hospital discharge or up to 9 months (corrected age). An internally developed

Randomized Trials of Retosiban Versus Placebo or Atosiban in Spontaneous Preterm Labor. The aim of this study is to assess the efficacy and safety of retosiban in spontaneous preterm labor (sPTL). Two multicenter, randomized, and double-blind trials compared retosiban with placebo and retosiban with atosiban in women with a singleton pregnancy and intact membranes in sPTL at 24 to 33 weeks );the atosiban-comparator trial enrolled 97 (March 2015-August 2017; 29% of target). Baseline participant characteristics were similar between treatments. In the placebo-controlled trial, mean gestational ages at randomization were 30.8 (retosiban,  = 10) and 30.5 weeks (placebo,  = 13), and mean times to delivery/treatment failure were 18.9 days (retosiban) and 11.1 days (placebo). Two and four neonates

Functionally Selective Inhibition of the Oxytocin Receptor by Retosiban in Human Myometrial Smooth Muscle. Novel small molecule inhibitors of the oxytocin receptor (OTR) may have distinct pharmacology and mode of action when compared with first-generation oxytocin antagonists when used for the prevention of preterm birth. The aim was to determine the mechanism of action of small molecule OTR antagonists retosiban and epelsiban compared with the currently used peptide-based compound atosiban. Human myometrial samples were obtained at cesarean section and subjected to pharmacological manipulations to establish the effect of antagonist binding to OTR on downstream signaling. Retosiban antagonism of oxytocin action in human myometrium was potent, rapid, and reversible. Inhibition of inositol 1,4,5

A Phase 1 Randomized, Placebo-Controlled Study Assessing the Pharmacokinetics, Safety, and Tolerability of Retosiban in Healthy, Nonpregnant Japanese Subjects. This study characterized the pharmacokinetics, safety, and tolerability of retosiban in healthy, nonpregnant Japanese women prior to the enrollment of Japanese women in preterm labor in phase 3 trials. This study had 2 cohorts. Cohort 1 was a double-blind, sponsor-open, randomized study in Japanese women. Cohort 2 was an open-label study in white women to compare the pharmacokinetics with those of Japanese women. Retosiban was administered as a 6 mg/h infusion for 24 hours, followed by a 12 mg/h infusion over the next 24 hours; each infusion was preceded by a 6 mg loading dose administered over 5 minutes. Plasma concentrations of retosiban

Retosiban prevents stretch-induced human myometrial contractility and delays labor in Cynomolgus monkeys. Stretch of the myometrium promotes its contractility and is believed to contribute to the control of parturition at term and to the increased risk of preterm birth in multiple pregnancies. To determine the effects of the putative oxytocin receptor (OTR) inverse agonist retosiban on (1 ) the contractility of human myometrial explants and (2) labor in nonhuman primates. Human myometrial biopsies were obtained at planned term cesarean, and explants were exposed to stretch in the presence and absence of a range of drugs, including retosiban. The in vivo effects of retosiban were determined in cynomolgus monkeys. Prolonged mechanical stretch promoted myometrial extracellular signal-regulated kinase

Treatment of spontaneous preterm labour with retosiban: a phase II pilot dose‐ranging study The aims of the present study were to investigate the maternal, fetal and neonatal safety and tolerability, pharmacodynamics and pharmacokinetics of intravenous (IV) retosiban in pregnant women with spontaneous preterm labour (PTL) between 34 and 35  weeks' gestation. In parts A and B of a three-part , double-blind, placebo-controlled, multicentre study, women were randomized 3:1 (Part A) or 2:1 (Part B) to either 12-h IV retosiban followed by a single dose of oral placebo (R-P) or 12-h IV placebo followed by single-dose oral retosiban (P-R). A total of 29 women were randomized; 20 to R-P and nine to P-R. An integrated analysis found that adverse events were infrequent in mothers/newborns

The effect of an oxytocin receptor antagonist (retosiban, GSK221149A) on the response of human myometrial explants to prolonged mechanical stretch. Multiple pregnancy is a major cause of spontaneous preterm birth, which is related to uterine overdistention. The objective of this study was to determine whether an oxytocin receptor antagonist, retosiban (GSK221149A), inhibited the procontractile effect of stretch on human myometrium. Myometrial biopsies were obtained at term planned cesarean delivery (n = 12). Each biopsy specimen was dissected into 8 strips that were exposed in pairs to low or high stretch (0.6 or 2.4 g) in the presence of retosiban (1 μM) or vehicle (dimethylsulfoxide) for 24 hours. Subsequently, we analyzed the contractile responses to KCl and oxytocin in the absence

Effect of Retosiban on Cardiac Repolarization in a Randomized, Placebo- and Positive-Controlled, Crossover Thorough QT/QTc Study in Healthy Men and Women. Retosiban is a small molecule oxytocin receptor antagonist that is under evaluation in clinical studies for treatment of spontaneous preterm labor. A Thorough QT/QTc study was conducted to evaluate the effect of retosiban on cardiac repolarization according to International Conference on Harmonization E14 guidance. This was a randomized, placebo- and positive-controlled, single-dose, crossover study of healthy men and women. All study participants received a 100 mg dose of retosiban (therapeutic target exposure), a 800 mg dose of retosiban (supratherapeutic target exposure), a 400 mg dose of moxifloxacin (positive control), and placebo

Treatment of spontaneous preterm labour with retosiban: a phase 2 proof-of-concept study. The aim was to investigate the efficacy and safety of intravenous retosiban in women with spontaneous preterm labour. This was a randomized, double-blind, placebo-controlled, phase 2 trial. Retosiban was administered intravenously for 48 h to women in spontaneous preterm labour between 30(0/7) and 35(6/7 )  weeks' gestation with an uncomplicated singleton pregnancy in an in-patient obstetric unit. Outcome measures were uterine quiescence (primary endpoint), days to delivery, preterm delivery and safety. Uterine quiescence was achieved in 62% of women who received retosiban (n = 30) compared with 41% who received placebo (n = 34). The relative risk (RR) was 1.53 (95% credible interval [CrI] 0.98, 2.48; NS

Novel Oxytocin Receptor Antagonists for Tocolysis - A Systematic Review of the Available Data on the Efficacy of Retosiban Novel Oxytocin Receptor Antagonists for Tocolysis - A Systematic Review of the Available Data on the Efficacy of Retosiban Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith

interactions of CNN1 with progesterone were investigated through LigPlot 2D. Further, molecular docking experimentation of CNN1 showed the significant interactions at S102, L105, A106, K123, Y124 with five selected PTB-drugs, Allylestrenol (-7.56 kcal/mol), Hydroxyprogesterone caproate (-8.19 kcal/mol), Retosiban (-9.43 kcal/mol), Ritodrine (-7.39 kcal/mol) and Terbutaline (-6.87 kcal/mol). Calponin-1 gene

and lactoferrin; Treatment: glyceryl trinitrate, retosiban, relcovaptan, human chorionic gonadotropin and Bryophyllum pinnatum extract). 107 candidates were in preclinical development. This analysis provides a drug-agnostic approach to assessing the potential of candidate medicines for spontaneous preterm birth. Research should be prioritised for high-potential candidates that are most likely to meet the real

medulla. Central inhibition of oxytocin receptors using atosiban (4.5 µg in 5 µl, i.c.v.), or retosiban (3 mg/kg, i.v.), prevented the MI-induced increase in SNA and reduced the incidence of ventricular arrhythmias and mortality. In conclusion, pre-autonomic oxytocin neurons can drive the increase in cardiac SNA following MI and peripheral administration of an oxytocin receptor blocker could

A Randomized Study Comparing the Efficacy and Safety of Retosiban Versus Atosiban for Women in Spontaneous Preterm Labour A Randomized Study Comparing the Efficacy and Safety of Retosiban Versus Atosiban for Women in Spontaneous Preterm Labour - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort. Hide glossary Record DetailSaved Studies Save this study WarningYou have reached the maximum number of saved studies (100).Please remove one or more studies before adding more. A Randomized Study Comparing the Efficacy and Safety of Retosiban Versus Atosiban for Women in Spontaneous Preterm Labour The safety and scientific validity of this study is the responsibility of the study sponsor and investigators

Follow up Study to Assess Long Term Safety and Outcomes in Infants Born to Mothers Participating in Retosiban Treatment Studies Follow up Study to Assess Long Term Safety and Outcomes in Infants and Children Born to Mothers Participating in Retosiban Treatment Studies - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization Login * Home * Search Results * Study Record DetailSaved Studies Save this study WarningYou have reached the maximum number of saved studies (100).Please remove one or more studies before adding more. Follow up Study to Assess Long Term Safety and Outcomes in Infants and Children Born to Mothers Participating in Retosiban Treatment Studies (ARIOS) The safety and scientific validity of this study

Study to Investigate the Pharmacokinetics (PK), Safety and Tolerability of Retosiban in Healthy Japanese Women Study to Investigate the Pharmacokinetics (PK), Safety and Tolerability of Retosiban in Healthy Japanese Women - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort. Hide glossary GlossaryStudy record managers Save this study WarningYou have reached the maximum number of saved studies (100).Please remove one or more studies before adding more. Study to Investigate the Pharmacokinetics (PK), Safety and Tolerability of Retosiban in Healthy Japanese Women The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been

A Phase III Efficacy and Safety Study of Intravenous Retosiban Versus Placebo for Women in Spontaneous Preterm Labor A Phase III Efficacy and Safety Study of Intravenous Retosiban Versus Placebo for Women in Spontaneous Preterm Labor - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort. Hide glossary GlossaryStudy DetailSaved Studies Save this study WarningYou have reached the maximum number of saved studies (100).Please remove one or more studies before adding more. A Phase III Efficacy and Safety Study of Intravenous Retosiban Versus Placebo for Women in Spontaneous Preterm Labor (NEWBORN-1) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing

This Study Will Investigate the Effect of Single Oral Doses of Retosiban on Cardiac Repolarization, With Moxifloxacin as a Positive Control in Healthy Volunteers. This Study Will Investigate the Effect of Single Oral Doses of Retosiban on Cardiac Repolarization, With Moxifloxacin as a Positive Control in Healthy Volunteers. - Full Text View - ClinicalTrials.gov Try the modernized * Terms and Conditions * Disclaimer * PRS Login * Home * Search Results * Study Record DetailSaved Studies Save this study WarningYou have reached the maximum number of saved studies (100).Please remove one or more studies before adding more. This Study Will Investigate the Effect of Single Oral Doses of Retosiban on Cardiac Repolarization, With Moxifloxacin as a Positive Control in Healthy

A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Retosiban (GSK221149) When Dosed With Efavirenz (EFZ) A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Retosiban (GSK221149) When Dosed With Efavirenz (EFZ) - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort. Hide glossary Record DetailSaved Studies Save this study WarningYou have reached the maximum number of saved studies (100).Please remove one or more studies before adding more. A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Retosiban (GSK221149) When Dosed With Efavirenz (EFZ) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators