Delving into the Latest Updates on Retosiban with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Retosiban (USAN), GSK-221149, GSK-221149A

Target

OXTR

Action

antagonists

Mechanism

OXTR antagonists(Oxytocin receptor antagonists)

Therapeutic Areas

Urogenital Diseases

Active Indication-

Inactive Indication

Obstetric Labor, PrematurePremature Ejaculation

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

License Organization-

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC27H34N4O5

InChIKeyPLVGDGRBPMVYPB-FDUHJNRSSA-N

CAS Registry820957-38-8

The study's primary objective is to demonstrate the superiority of retosiban to prolong pregnancy and improve neonatal outcomes compared with placebo. It is a Phase III, randomized, double-blind, parallel-group, multicenter study and will be conducted in approximately 900 females, aged 12 to 45 years, with an uncomplicated, singleton pregnancy and intact membranes in preterm labor between 24^0/7 and 33^6/7 weeks of gestation. Eligible maternal subjects will be randomly assigned in a 1:1 ratio to receive either retosiban IV infusion or placebo IV infusion over 48 hours. If not previously administered, antenatal corticosteroid treatment should be administered as either (1) two 12-mg doses of betamethasone given intramuscularly 24 hours apart or (2) four 6-mg doses of betamethasone administered intramuscularly every 12 hours. A single rescue course of antenatal corticosteroids is permitted if the antecedent treatment was at least 7 days prior to study enrolment. Investigators have discretion to use a standardized regimen of magnesium sulphate, as well as intrapartum antibiotic prophylaxis for perinatal group B streptococcal infection. Prior to randomization, each subject will be stratified by progesterone treatment and gestational age. The progesterone strata will consist of subjects on established progesterone therapy or subjects not on established progesterone therapy at Screening. The study will comprise 6 phases: Screening, Inpatient Randomized Treatment, Post Infusion Assessment, Delivery, Maternal Post-Delivery Assessment, and Neonatal Medical Review. The duration of any subject's (maternal or neonatal) participation in the study will be variable and dependent on gestational ages (GA) at study entry and the date of delivery.

Start Date29 Feb 2016

Sponsor / Collaborator

GSK Plc

[+1]

NCT02292784

/ CompletedPhase 3

Follow-Up Study to Assess Long-Term Safety and Outcomes in Infants and Children Born to Mothers Participating in Retosiban Treatment Studies

The primary objective of this study is to assess the safety and outcomes of infants and children who were exposed to retosiban or comparator in utero in the Phase III spontaneous preterm labor (SPTL) treatment studies, to provide assurance that treatment is not associated with significant adverse outcomes in early childhood. The enrolled infants and children will be followed at pre-specified intervals until they reach 24 months chronological age. This study does not require medical interventions or study visits to an investigational site, instead, parents or legal guardians will be prompted at certain time points to complete developmental questionnaires and other data on their children's health status via an electronic device. Data collected during the infant and child follow up study will be managed by a centralized research coordinating center (RCC). Regionally based pediatricians will serve as study principal investigators (referred to as RCC-PIs) for this study. All communications the RCC-PI has with the parent/legal guardian or the child's health care provider (HCP) will occur remotely; there will be no clinic visits.

Start Date01 Jun 2015

Sponsor / Collaborator

GSK Plc

[+1]

NCT02292771

/ TerminatedPhase 3

Randomized, Double-blind, Multicenter, Phase III Study Comparing the Efficacy and Safety of Retosiban Versus Atosiban Therapy for Women in Spontaneous Preterm Labor

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.

Start Date16 Mar 2015

Sponsor / Collaborator

GSK Plc

[+1]

100 Clinical Results associated with Retosiban

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100 Translational Medicine associated with Retosiban

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100 Patents (Medical) associated with Retosiban

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30

Literatures (Medical) associated with Retosiban

01 Jul 2023·American journal of perinatologyQ4 · MEDICINE

Safety and Outcomes in Infants Born to Mothers Participating in Retosiban Treatment Trials: ARIOS Follow-up Study

Q4 · MEDICINE

Article

Author: Pimenta, Jeanne M. ; Beach, Kathleen J. ; Saade, George R. ; Correa, Erika Ochoa ; Powell, Marcy ; Scott, Rhona ; Thornton, Steve ; Haque, Nazneen ; Snidow, Jerry ; Miller, Diane

Objective 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. Study Design 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 questionnaire detailing medical conditions, mortality and resource use (Child Health Inventory; CHI), Ages and Stages Questionnaire-3 (ASQ-3), Modified Checklist for Autism in Toddlers–Revised with Follow-Up, and Child Behavior Checklist for Ages 1.5 to 5 were completed remotely by parents or legal guardians at prespecified intervals. Serious adverse events (SAEs) were primarily captured via CHI. No comparative statistical analysis was conducted between treatment arms. Results A total of 49 (86%) infants who had received retosiban and 49 (78%) infants who had received a comparator were enrolled in ARIOS. No deaths occurred during the study. Nine infants experienced SAEs: 6/49 (12.2%) infants in the comparators group and 3/49 (6.1%) in the retosiban group. Of the nine SAEs, seven were due to infections, three, and four in the retosiban and comparators groups, respectively. Based on ASQ-3 score, the incidence of neurodevelopmental delay at 18 and 24 months were 0/18 (0%) and 2/25 (8%) with retosiban and 7/22 (31.8%) and 3/21 (14.3%) with comparator, respectively. Conclusion The current study showed no unexpected adverse outcome or impairment with retosiban based on safety monitoring and neurodevelopment assessments. No further follow-up is intended owing to the discontinuation of clinical development of retosiban. Key Points

02 Sep 2021·Current medical research and opinionQ4 · MEDICINE

Novel oxytocin receptor antagonists for tocolysis: a systematic review and meta-analysis of the available data on the efficacy, safety, and tolerability of retosiban

Q4 · MEDICINE

Review

Author: Ulibarri, Hollie ; Cieminski, Kaitlynne ; Marchand, Greg ; Ware, Kelly ; King, Alexa ; Ruuska, Alexandra D. ; Blumrick, Richard ; Masoud, Ahmed Taher ; Calteux, Nicolas ; Ruther, Stacy ; Sainz, Katelyn ; Brazil, Giovanna

OBJECTIVE:

To assess the efficacy, safety, and tolerability of retosiban-a novel tocolytic unavailable in the US-in the management of preterm labor.

METHODS:

We searched ClinicalTrials.Gov, MEDLINE, PubMed, SCOPUS, Web of Science, and the Cochrane Library for relevant clinical trials using the terms "retosiban" and "preterm labor" through 09/2020. We included all published randomized clinical trials (three) that compared retosiban to placebo for preterm labor, excluding conferences, books, reviews, posters, case reports, and animal studies. We analyzed homogeneous data under the fixed-effects model and heterogeneous data under the random-effects model.

RESULTS:

We included all randomized clinical trials addressing this topic, which ultimately resulted in three trials with a total of 116 patients. There were no significant differences between retosiban and placebo in births at term (RR = 0.41, p = .02), births ≤7 days from the first study treatment (RR = 0.59, p = .23), or administration of rescue tocolytic (RR = 0.36, p = .07); the maternal adverse events of headache, anemia, constipation, or urinary tract infection (p > .05); or neonatal outcomes of Apgar score at 1 min (p = .88) or 5 min (p = .69), weight (p = .23), head circumference (p = .55), malnutrition (p = .27), hyperbilirubinemia (RR = 0.56, p = .21), jaundice (RR = 1.21, p = .84), respiratory distress (RR = 0.53, p = .49), or tachypnea (RR = 0.40, p = .42).

CONCLUSION:

With the limited high quality evidence available, retosiban demonstrates no clear benefit over placebo in the management of preterm labor. Nevertheless, its favorable safety profile, oral bioavailability, and novel mechanism of action and the limited number of studies available for review warrant further analysis.

01 Aug 2021·American journal of perinatologyQ4 · MEDICINE

Erratum: Randomized Trials of Retosiban versus Placebo or Atosiban in Spontaneous Preterm Labor

Q4 · MEDICINE

Article

Author: Powell, Marcy ; Saade, George ; Shennan, Andrew ; Beach, Kathleen J. ; Parilla, Barbara V. ; Komatsu, Yosuke ; Thornton, Steven ; Liu, Feng ; McKain, Laura ; Hadar, Eran ; Snidow, Jerry ; Montague, Timothy H.

100 Deals associated with Retosiban

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External Link

KEGG	Wiki	ATC	Drug Bank
D08986	Retosiban	-	DB11818

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Obstetric Labor, Premature	Phase 3	United States	GSK Plc	16 Mar 2015
Obstetric Labor, Premature	Phase 3	Belgium	GSK Plc	16 Mar 2015
Obstetric Labor, Premature	Phase 3	Germany	GSK Plc	16 Mar 2015
Obstetric Labor, Premature	Phase 3	Israel	GSK Plc	16 Mar 2015
Obstetric Labor, Premature	Phase 3	Italy	GSK Plc	16 Mar 2015
Obstetric Labor, Premature	Phase 3	Mexico	GSK Plc	16 Mar 2015
Obstetric Labor, Premature	Phase 3	Spain	GSK Plc	16 Mar 2015
Obstetric Labor, Premature	Phase 3	Sweden	GSK Plc	16 Mar 2015
Obstetric Labor, Premature	Phase 3	United Kingdom	GSK Plc	16 Mar 2015
Premature Ejaculation	Phase 1	United States	GSK Plc	01 Mar 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02292784 (ARIOS, Pubmed \| Am J Perinatol)	Phase 3	-	-	Comparator (Placebo/Atosiban)	hlkqxwlfac(mvzheoxgic) = hphaagdtfi sdfvfzafcd (kthfplsved )	-	05 Aug 2021
NCT02292784 (ARIOS, CTgov)	Phase 3	Obstetric Labor, Premature	98	Placebo (Placebo (200719 Study))	kuobpshutq = aemblvqpyl flflcmrbqs (phxfrjltim, carmndbzjv - yimgyfyukf) View more	-	09 Jul 2020
				Atosiban (Atosiban (200721 Study))	kuobpshutq = rnyzkilqrc flflcmrbqs (phxfrjltim, ytrwesaqdk - mjdrutlano) View more
NCT02292771 (CTgov)	Phase 3	Obstetric Labor, Premature	97	Retosiban (Retosiban)	kndqzeleve(sxpyxepxhb) = cihqezwwth vvybrlcvgt (abxuspqmrc, 2.990) View more	-	10 Sep 2018
				Atosiban (Atosiban)	kndqzeleve(sxpyxepxhb) = qzbencqtrn vvybrlcvgt (abxuspqmrc, 2.531) View more
NCT02377466 (NEWBORN-1, CTgov)	Phase 3	Obstetric Labor, Premature	25	Placebo IV infusion (Placebo)	yewtlydaoc(qgclxkztbb) = ragmsdhkiz wgsgvklkcc (dmhynigvlp, 14.987) View more	-	19 Jul 2018
				Retosiban IV infusion (Retosiban)	yewtlydaoc(qgclxkztbb) = fwtbzdfvjt wgsgvklkcc (dmhynigvlp, 22.993) View more
NCT00404768 (Pubmed \| Br J Clin Pharmacol) Manual	Phase 2	Obstetric Labor, Premature	64	retosiban	mcumfkcojt(gpvsuiuyvr) = crdkrnljzr xrnoelikdw (qydguchgvt ) View more	Positive	01 Oct 2015
				Placebo	mcumfkcojt(gpvsuiuyvr) = sppffmxjpr xrnoelikdw (qydguchgvt ) View more
NCT01702376 (Pubmed \| Clin Ther)	Phase 1	-	52	Retosiban 100 mg	lrvjqvcyut(xtpxyejemb) = jvqbsbetxy qxtmvgqovr (hpwwtzjaxi )	-	01 Jul 2015
				Retosiban 800 mg	lrvjqvcyut(xtpxyejemb) = dptrzkulnf qxtmvgqovr (hpwwtzjaxi )