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

Phase 2
Terminated
Conditions
Pre-eclampsia
Interventions
Drug: Placebo
Registration Number
NCT01566630
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
Female
Target Recruitment
3
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboIn 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
RLX030RLX030In 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.
Primary Outcome Measures
NameTimeMethod
Number of Patients With Adverse Events, Serious Adverse and Death During Part 1 of the StudyPrior to delivery until 4-6 weeks post partum (maximum of 8 weeks)

Safety and tolerability was assessed by adverse events/serious adverse event and death monitoring.

Number of Patients With Abnormalities in Fetal Cardiotocography and Biophysical ProfileRandomization to delivery (maximum of 3 weeks)
Pharmacokinetics of RLX030: Area Under the Blood Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)-Part 1Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1

Blood concentrations of RLX-030 was assayed to determine this PK parameter.

Change From Baseline in Maternal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Part 1of the Study (Part 1)From baseline to during treatment period of a maximum 72 hours infusion prior to delivery until 4-6 weeks post partum in part 1 (maximum of 8 weeks)

Maternal safety assessment to monitor pre-eclampsia by checking blood pressure during 72 hour treatment period as well as post-dose.

Decrease in Utero-placental Blood Flow (Part 1)During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)

Blood flow to the fetus was monitored using via a Doppler.

Number of Patients With Abnormalities in Birth Weight, Gestational Age, Appearance, Pulse, Grimace, Activity, Respiration (APGAR) Score, Umbilical Cord Gases, and Days in Neonatal Intensive Care Unit (NICU)up to 4 - 6 weeks post partum (maximum of 8 weeks )
Pharmacokinetics of RLX030: Area Under the Blood Concentration-time Curve From Time Zero to Infinity (AUCinf)-Part 1Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1

Blood concentrations of RLX-030 was assayed to determine this PK parameter.

Pharmacokinetics of RLX030: Mean Residence Time (MRT)Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1

Blood concentrations of RLX-030 was assayed to determine this PK parameter.

Change From Baseline on Maternal Proteinuria (Part 1)From baseline to during treatment period of a maximum 72 hours infusion prior to delivery until 4-6 weeks post partum in part 1 (maximum of 8 weeks)

Pre-eclampsia was monitored by checking levels of protein in urine and by urinary protein/creatinine ratio (UPCR)

Improvement in Renal Function Assessed by Increase in Creatinine ClearanceFrom randomization until 4-6 weeks post partum (maximum 8 weeks)
Rate of Spontaneous Delivery and/or Mode of DeliveryFrom randomization to delivery (maximum of 3 weeks)
Number of Patients With Absence of Anti-serelaxin AntibodiesFrom Randomization until 4-6 weeks post partum (maximum of 8 weeks)
Pharmacokinetics of RLX030: Blood Concentration at 24 Hour (C 0-24h) After Administration- Part 1Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1

Blood concentrations of RLX-030 was assayed to determine this PK parameter.

Change From Baseline in Mean Maternal Arterial Pressure (Part 1)From baseline to during treatment period of a maximum 72 hours infusion prior to delivery until 4-6 weeks post partum in part 1 (maximum of 8 weeks)

Maternal safety assessment to monitor pre-eclampsia by checking mean arterial pressure during 72 hour treatment period as well as post-dose.

Change in Fetal Heart Rate (Part 1)During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)

Heart rate of fetus was monitored continuously throughout 72 hour treatment period using a cardiotocograph.

Pharmacokinetics of RLX030: Terminal Elimination Half-life (T1/2)- Part 1Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1

Blood concentrations of RLX-030 was assayed to determine this PK parameter.

Secondary Outcome Measures
NameTimeMethod
Mean Number of Days Before DeliveryFrom randomization until delivery (maximum of 3 weeks)

Trial Locations

Locations (1)

Novartis Investigative Site

🇮🇹

Modena, MO, Italy

Novartis Investigative Site
🇮🇹Modena, MO, Italy

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