title: Effects of the Oral Oxytocin Receptor Antagonist Tocolytic OBE001 on Reproduction in Rats.
abstract: BACKGROUND
  OBE001 is a novel, orally active nonpeptide oxytocin receptor antagonist under development for the treatment of preterm labor and improvement in embryo implantation and pregnancy rate in assisted reproductive technology (ART). The reproductive safety of OBE001 was evaluated in customized fertility embryonic development (FER)/early embryonic development (EED) and fetal development (FD) and pre/postnatal development (PPN) studies mimicking clinical exposure scenarios.
  
  
  METHODS
  Oral OBE001 was evaluated at doses of 37.5, 75, and 125 mg/kg/d in female rats during a FER/EED study (from premating to implantation) and throughout FD during a FD/PPN study.
  
  
  RESULTS
  No OBE001 effects were observed during the FER/EED study. The FD/PPN study did not result in adverse OBE001 effects in females allowed to litter, their offspring, and second-generation fetuses. Females at 125 mg/kg/d who underwent cesarean section before term had slight reductions in body weights and food consumption, and associated fetuses had slightly delayed ossification of skull bones, which was not adverse in the absence of effects on live offspring.
  
  
  CONCLUSIONS
  OBE001 at up to 125 mg/kg/d had no effects on EED and no adverse effects on FD and postnatal development of rats. These results constitute an important step toward the development of OBE001 in preterm labor and ART indications.
authors.affiliation: ObsEva SA, Geneva, Switzerland oliver.pohl@obseva.ch.
authors.forename: Oliver
authors.initials: O
authors.lastname: Pohl
authors.affiliation: Covance Laboratories Ltd, Harrogate, United Kingdom.
authors.forename: Deborah
authors.initials: D
authors.lastname: Perks
authors.affiliation: Covance Laboratories Ltd, Harrogate, United Kingdom.
authors.forename: Jon
authors.initials: J
authors.lastname: Rhodes
authors.affiliation: RBM S.p.A., Istituto di Ricerche Biomediche A. Marxer, Colleretto Giacosa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Comotto
authors.affiliation: Covance Laboratories Ltd, Harrogate, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Baldrick
authors.affiliation: ObsEva SA, Geneva, Switzerland.
authors.forename: André
authors.initials: A
authors.lastname: Chollet
mesh_terms: D000284:Administration, Oral; D000818:Animals; D005260:Female; D008297:Male; D010091:Oximes / Q000008:administration & dosage*; D011247:Pregnancy; D011759:Pyrrolidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors* / Q000502:physiology; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology; D015149:Tocolytic Agents / Q000008:administration & dosage*
chemical_list: C000604229:OBE001; D010091:Oximes; D011759:Pyrrolidines; D018045:Receptors, Oxytocin; D015149:Tocolytic Agents
keywords: OBE001; assisted reproductive technology; preterm labor; rat; reproductive safety