Use of barusiban in a novel study design for evaluation of tocolytic agents in pregnant and neonatal monkeys, including behavioural and immunological endpoints☆

The oxytocin receptor antagonist barusiban, currently being developed for treatment of preterm labour, was investigated in pregnant cynomolgus monkeys with a 9-month postnatal follow-up of their offspring. The nature of barusiban, its indication, and the potential exposure of pre- and postnatal infants entailed the design of a unique protocol to investigate all aspects of maternal and offspring well-being. Barusiban was administered to the mothers from gestation day 85 until delivery with daily subcutaneous dosages up to 2.5mg/kg body weight/day. There were no test article-related effects seen in the mothers at any time during the study. The postnatal examination of offspring included routine toxicological parameters, as well as specialised investigation of the immune, cardiovascular, renal and central nervous systems, including a full behavioural assessment. A full pathology examination of offspring was performed at the end of the 9-month postnatal period. No adverse infant findings occurred.