An Adaptive Multicentre, Randomized, Partially Double-blind, Placebo-controlled Study to Assess the Safety, PK and PD/Efficacy of RLX030 in Women With Pre-eclampsia
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- Number of Patients With Adverse Events, Serious Adverse and Death During Part 1 of the Study
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 40 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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: Placebo (Drug)
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: RLX030 (Drug)
Outcomes
Primary Outcomes
Number of Patients With Adverse Events, Serious Adverse and Death During Part 1 of the Study
Time Frame: Prior 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 Profile
Time Frame: Randomization 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 1
Time Frame: 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 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 (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)
Time Frame: 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)
Time Frame: 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 1
Time Frame: 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.
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
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
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 (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 Clearance
Time Frame: From randomization until 4-6 weeks post partum (maximum 8 weeks)
Rate of Spontaneous Delivery and/or Mode of Delivery
Time Frame: From randomization to delivery (maximum of 3 weeks)
Number of Patients With Absence of Anti-serelaxin Antibodies
Time Frame: From 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 1
Time Frame: 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 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 (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)
Time Frame: 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 1
Time Frame: 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.
Secondary Outcomes
- Mean Number of Days Before Delivery(From randomization until delivery (maximum of 3 weeks))