Safety and Efficacy of RLX030 in Pregnant Women With Pre- Eclampsia

• Number of patients with adverse events, serious adverse and death during part 1 of the study [ Time Frame: Prior to delivery until 4-6weeks post partum ] [ Designated as safety issue: Yes ]
  Safety and tolerability will be assessed by adverse events/serious adverse event and death monitoring.
• Change from baseline in maternal systolic blood pressure (SBP) and diastolic blood pressure (DBP) in part 1of the study (part 1) [ Time Frame: From baseline to during treatment period of a maximum 72 hours infusion prior to delivery until 4-6 weeks post partum in part 1 ] [ Designated as safety issue: Yes ]
  Maternal safety assessment to monitor pre-eclampsia by checking blood pressure during 72 hour treatment period as well as post-dose.
• Change from baseline in mean maternal arterial pressure (part 1) [ Time Frame: From baseline to during treatment period of a maximum 72 hours infusion prior to delivery until 4-6 weeks post partum in part 1 ] [ Designated as safety issue: Yes ]
  Maternal safety assessment to monitor pre-eclampsia by checking mean arterial pressure during 72 hour treatment period as well as post-dose.
• Change from baseline on maternal proteinuria (Part 1) [ Time Frame: From baseline to during treatment period of a maximum 72 hours infusion prior to delivery until 4-6 weeks post partum in part 1 ] [ Designated as safety issue: Yes ]
  Pre-eclampsia will also be monitored by checking levels of protein in urine and by urinary protein/creatinine ratio (UPCR)
• Decrease in utero-placental blood flow (Part 1) [ Time Frame: During treatment period of a maximum 72 hours infusion prior to delivery and during delivery in part 1 ] [ Designated as safety issue: Yes ]
  Blood flow to the fetus will be monitored using via a Doppler.
• Change in fetal heart rate (Part 1) [ Time Frame: during treatment period of a maximum 72 hours infusion prior to delivery and during delivery in part 1 ] [ Designated as safety issue: Yes ]
  Heart rate of fetus will be monitored continuously throughout 72 hour treatment period using a cardiotocographer.
• Pharmacokinetics of RLX030: area under the blood concentration-time curve from time zero to infinity (AUCinf)-Part 1 [ Time Frame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1 ] [ Designated as safety issue: No ]
  blood concentrations of RLX-030 will be assayed to determine AUCinf (if appropriate)
• Pharmacokinetics of RLX030: area under the blood concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)-Part 1 [ Time Frame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1 ] [ Designated as safety issue: No ]
  Blood concentrations of RLX-030 will be assayed to determine AUClast (if appropriate)
• Pharmacokinetics of RLX030: blood concentration at 24 hour (C 0-24h) after administration- Part 1 [ Time Frame: 24 hours after initiation of infusion during part 1 ] [ Designated as safety issue: No ]
  blood concentrations of RLX-030 will be assayed to determine C 0-24h (if appropriate).
• Pharmacokinetics of RLX030: terminal elimination half-life (T1/2)- Part 1 [ Time Frame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1 ] [ Designated as safety issue: No ]
  Blood concentrations of RLX-030 will be obtained.
• Pharmacokinetics of RLX030: mean residence time (MRT) [ Time Frame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1 ] [ Designated as safety issue: No ]
  Blood concentrations of RLX-030 will be assayed to determine MRT (if appropriate)

This study is designed in two parts. Part 1 will assess the safety and tolerability of different doses of RLX030 when given to pregnant women with pre- eclampsia (elevated blood pressure with protein in urine). Part 2 will assess whether an optimal dose of RLX030 can prolong pregnancy in women with pre-eclampsia.

• Drug: Placebo
  Placebo to RLX030 as intravenous infusion for 72 hours
• Drug: RLX030
  RLX030 1 mg/mL vials

• Experimental: RLX030

  In part 1, within each cohort, two (2) patients per cohort will be treated open label with RLX030 and two (2) patients will be treated double blind with RLX030 as intravenous infusion for 72 hours. There will be 3 cohorts in part 1 with different doses of RLX030.

  In part 2, there is no open label treatment on RLX030. In part 2, patients will be randomized in a double-blind fashion to this arm with the optimal dose of RLX030 as intravenous infusion for 72 hours as determined from part 1.

  Intervention: Drug: RLX030
• Placebo Comparator: Placebo

  In part 1, equal number of subjects will be treated with matching placebo of RLX030 as intravenous infusion for 72 hours in 3 cohorts.

  In part 2, patients will be treated with matching placebo of RLX030 as intravenous infusion for 72 hours

  Intervention: Drug: Placebo

Inclusion criteria:

• Women that are 28- 33 weeks (+4 days) pregnant with a diagnosis of pre- eclampsia or superimposed pre-eclampsia requiring hospitalization
• Fetus deemed in reasonably good health

Exclusion criteria:

• Severe hypertension and /or those receiving anti-hypertensive treatment at time of enrollment
• Severe headaches, visual changes, or altered mentation
• Upper abdominal pain, nausea, or vomiting
• Low blood platelet count
• Diagnosis of a seizure disorder that requires chronic medication
• Those receiving active anti-coagulation therapy
• Pre-gestational diabetes (Type 1 or Type 2)
• Allergy to magnesium sulfate or steroids
• Known major fetal anomaly
• Multifetal gestation

Other protocol-defined inclusion/exclusion criteria may apply