The Safety, Tolerability And Metabolism Of GSK221149A, In Pregnant Women (30-36 Weeks), In Pre-Term Labor

• Maternal safety and tolerability will be assessed by ECGs, blood pressure, heart rate, fetal ultrasound and blood tests, over 24 hours.
• The progression of contractions and the fetal heart rate will be continuously monitored, over 24 hours

• Neonatal Apgar Scores (at birth) and weight gain, head circumference, length and development measured at 4 - 6 weeks of age (benchmarked to establish norms)
• Pharmacokinetic parameters

Pre-Term Labor (prior to 37 weeks gestation) is the largest single cause of infant morbidity and mortality and is frequently associated with long-term disability. Oxytocin is a hormone produced by the body during labor. GSK221149A is an experimental drug that will be used to block the effects of oxytocin, and therefore pause or prevent contractions. In this study, patients with preterm labor will be given an intravenous infusion of GSK221149A over approximately 12 hours followed by an oral tablet in Parts A and B. In part C of this study, patients with preterm labor will be give an intravenous infusion of GSK221149A over approximately 48 hours. The use of a rescue tocolytic is allowed in the study.

A randomized, double-blind, placebo-controlled, dose ranging study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of GSK221149A administered intravenously and to investigate the pharmacokinetics of GSK221149A administered orally to healthy, pregnant females with uncomplicated pre-term labor between 300/7 and 356/7 weeks' gestation

• Drug: GSK221149A
  6mg/h and 12 mg/h
  Other Name: GSK221149A
• Drug: Placebo
  Matched Placebo to Drug

• Experimental: Treatment
  GSK221149A
  Intervention: Drug: GSK221149A
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo

Inclusion criteria:

• Healthy pregnant females, 30 -36 weeks pregnant, without ruptured membranes
• 18-45 inclusive
• Symptoms of pre-term labor, (greater than or equal to 6 uterine contractions per hour, each of which at least 30 sec in duration, with cervical dilatation of less than or equal to 4 cm, (measured by tocodynamometry).

Exclusion criteria:

• Any clinically relevant abnormality identified on the screening examination or any other medical condition or circumstance making the patient (mother and/or fetus) unsuitable for participation in the study
• Any clinically relevant pre-existing or pregnancy-related co-morbid condition that may affect maternal pregnancy outcome or neonatal outcome (eg. hypertension, diabetes mellitus, bleeding/clotting diathesis)