Back to resultsSafety and Efficacy of RLX030 in Pregnant Women With Pre- Eclampsia
Primary Purpose
Pre-eclampsia
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
RLX030
Sponsored by
About this trial
This is an interventional treatment trial for Pre-eclampsia focused on measuring human recombinant RLX030, Pre-eclampsia, hemodynamics, Pharmacokinetics
Eligibility Criteria
Key Inclusion criteria:
- Written informed consent was obtained before any assessment was performed.
- Women at 18 to 40 years of age with a pregnancy 28 weeks (0 days) and 33 weeks (+4 days) gestational age. Gestational age was based on mother's last menstruation; if last menstruation was unknown, an alternative method was used as applicable and was documented in the (electronic) Case Report/Record Form [(e)CRF].
- Women with a diagnosis of pre-eclampsia or superimposed pre-eclampsia requiring hospitalization. Pre-eclampsia was defined as new onset of hypertension (SBP ≥ 140 or DBP ≥ 90 mmHg) or gestational hypertension accompanied by proteinuria (>= 0.3 g/24h) after 20 weeks of gestation. Superimposed pre-eclampsia was defined as chronic hypertension with new onset of proteinuria after 20 weeks of gestation.
- Reassuring fetal testing (cardiotocography and biophysical profile)
Key Exclusion criteria:
- Severe hypertension (SBP ≥ 160 mmHg or DBP ≥ 110 mmHg) and /or those receiving anti-hypertensive treatment at time of randomization.
- Clinically relevant electrocardiogram (ECG) abnormalities at screening excluding those abnormalities commonly seen in pregnancy according to the Investigator.
- Symptoms indicative of severe pre-eclampsia or HELLP syndrome (Hemolysis, Elevated Liver enzymes, and Low Platelet count) for which immediate delivery of the baby may be indicated. Symptoms include persistent CNS symptoms (severe headaches, visual changes, altered mentation), persistent right upper quadrant or epigastric pain, nausea or vomiting, severe thrombocytopenia (<100,000/mm3) and abnormal (> 2X upper limit of normal) liver enzymes (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]).
- Eclampsia during current pregnancy, vaginal bleeding present at screening, abruptio placentae, oligohydramnios
- Current diagnosis of a seizure disorder that requires chronic medication.
- Pre-gestational diabetes (Type 1 or Type 2) with or without diabetic retinopathy. Diagnosis (previous or current) of gestational diabetes, regardless of treatment, was allowed
- Known allergy to magnesium sulfate or steroids.
- Multifetal gestation, known major fetal anomaly, intrauterine growth restriction (<5th percentile).
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
RLX030
Placebo
Arm Description
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.
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
Outcomes
Primary Outcome Measures
Number of Patients With Adverse Events, Serious Adverse and Death During Part 1 of the Study
Safety and tolerability was 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)
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)
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)
Pre-eclampsia was monitored by checking levels of protein in urine and by urinary protein/creatinine ratio (UPCR)
Decrease in Utero-placental Blood Flow (Part 1)
Blood flow to the fetus was monitored using via a Doppler.
Change in Fetal Heart Rate (Part 1)
Heart rate of fetus was monitored continuously throughout 72 hour treatment period using a cardiotocograph.
Improvement in Renal Function Assessed by Increase in Creatinine Clearance
Rate of Spontaneous Delivery and/or Mode of Delivery
Number of Patients With Absence of Anti-serelaxin Antibodies
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)
Number of Patients With Abnormalities in Fetal Cardiotocography and Biophysical Profile
Pharmacokinetics of RLX030: Area Under the Blood Concentration-time Curve From Time Zero to Infinity (AUCinf)-Part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Pharmacokinetics of RLX030: Area Under the Blood Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)-Part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Pharmacokinetics of RLX030: Blood Concentration at 24 Hour (C 0-24h) After Administration- Part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Pharmacokinetics of RLX030: Terminal Elimination Half-life (T1/2)- Part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Pharmacokinetics of RLX030: Mean Residence Time (MRT)
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Secondary Outcome Measures
Mean Number of Days Before Delivery
Full Information
NCT ID
NCT01566630
First Posted
March 27, 2012
Last Updated
October 12, 2015
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01566630
Brief Title
Safety and Efficacy of RLX030 in Pregnant Women With Pre- Eclampsia
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Terminated
Why Stopped
Novartis terminated this study due to internal, strategic decisions.
Study Start Date
May 2013 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
August 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pre-eclampsia
Keywords
human recombinant RLX030, Pre-eclampsia, hemodynamics, Pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RLX030
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to RLX030 as intravenous infusion for 72 hours
Intervention Type
Drug
Intervention Name(s)
RLX030
Intervention Description
RLX030 1 mg/mL vials
Primary Outcome Measure Information:
Title
Number of Patients With Adverse Events, Serious Adverse and Death During Part 1 of the Study
Description
Safety and tolerability was assessed by adverse events/serious adverse event and death monitoring.
Time Frame
Prior to delivery until 4-6 weeks post partum (maximum of 8 weeks)
Title
Change From Baseline in Maternal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Part 1of the Study (Part 1)
Description
Maternal safety assessment to monitor pre-eclampsia by checking blood pressure during 72 hour treatment period as well as post-dose.
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)
Title
Change From Baseline in Mean Maternal Arterial Pressure (Part 1)
Description
Maternal safety assessment to monitor pre-eclampsia by checking mean arterial pressure during 72 hour treatment period as well as post-dose.
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)
Title
Change From Baseline on Maternal Proteinuria (Part 1)
Description
Pre-eclampsia was monitored by checking levels of protein in urine and by urinary protein/creatinine ratio (UPCR)
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)
Title
Decrease in Utero-placental Blood Flow (Part 1)
Description
Blood flow to the fetus was monitored using via a Doppler.
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)
Title
Change in Fetal Heart Rate (Part 1)
Description
Heart rate of fetus was monitored continuously throughout 72 hour treatment period using a cardiotocograph.
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)
Title
Improvement in Renal Function Assessed by Increase in Creatinine Clearance
Time Frame
From randomization until 4-6 weeks post partum (maximum 8 weeks)
Title
Rate of Spontaneous Delivery and/or Mode of Delivery
Time Frame
From randomization to delivery (maximum of 3 weeks)
Title
Number of Patients With Absence of Anti-serelaxin Antibodies
Time Frame
From Randomization until 4-6 weeks post partum (maximum of 8 weeks)
Title
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 )
Title
Number of Patients With Abnormalities in Fetal Cardiotocography and Biophysical Profile
Time Frame
Randomization to delivery (maximum of 3 weeks)
Title
Pharmacokinetics of RLX030: Area Under the Blood Concentration-time Curve From Time Zero to Infinity (AUCinf)-Part 1
Description
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Time Frame
Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Title
Pharmacokinetics of RLX030: Area Under the Blood Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)-Part 1
Description
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Time Frame
Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Title
Pharmacokinetics of RLX030: Blood Concentration at 24 Hour (C 0-24h) After Administration- Part 1
Description
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Time Frame
Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Title
Pharmacokinetics of RLX030: Terminal Elimination Half-life (T1/2)- Part 1
Description
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Time Frame
Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Title
Pharmacokinetics of RLX030: Mean Residence Time (MRT)
Description
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Time Frame
Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Secondary Outcome Measure Information:
Title
Mean Number of Days Before Delivery
Time Frame
From randomization until delivery (maximum of 3 weeks)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion criteria:
Written informed consent was obtained before any assessment was performed.
Women at 18 to 40 years of age with a pregnancy 28 weeks (0 days) and 33 weeks (+4 days) gestational age. Gestational age was based on mother's last menstruation; if last menstruation was unknown, an alternative method was used as applicable and was documented in the (electronic) Case Report/Record Form [(e)CRF].
Women with a diagnosis of pre-eclampsia or superimposed pre-eclampsia requiring hospitalization. Pre-eclampsia was defined as new onset of hypertension (SBP ≥ 140 or DBP ≥ 90 mmHg) or gestational hypertension accompanied by proteinuria (>= 0.3 g/24h) after 20 weeks of gestation. Superimposed pre-eclampsia was defined as chronic hypertension with new onset of proteinuria after 20 weeks of gestation.
Reassuring fetal testing (cardiotocography and biophysical profile)
Key Exclusion criteria:
Severe hypertension (SBP ≥ 160 mmHg or DBP ≥ 110 mmHg) and /or those receiving anti-hypertensive treatment at time of randomization.
Clinically relevant electrocardiogram (ECG) abnormalities at screening excluding those abnormalities commonly seen in pregnancy according to the Investigator.
Symptoms indicative of severe pre-eclampsia or HELLP syndrome (Hemolysis, Elevated Liver enzymes, and Low Platelet count) for which immediate delivery of the baby may be indicated. Symptoms include persistent CNS symptoms (severe headaches, visual changes, altered mentation), persistent right upper quadrant or epigastric pain, nausea or vomiting, severe thrombocytopenia (<100,000/mm3) and abnormal (> 2X upper limit of normal) liver enzymes (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]).
Eclampsia during current pregnancy, vaginal bleeding present at screening, abruptio placentae, oligohydramnios
Current diagnosis of a seizure disorder that requires chronic medication.
Pre-gestational diabetes (Type 1 or Type 2) with or without diabetic retinopathy. Diagnosis (previous or current) of gestational diabetes, regardless of treatment, was allowed
Known allergy to magnesium sulfate or steroids.
Multifetal gestation, known major fetal anomaly, intrauterine growth restriction (<5th percentile).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36604
Country
United States
Facility Name
Novartis Investigative Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40503
Country
United States
Facility Name
Novartis Investigative Site
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Novartis Investigative Site
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555-0587
Country
United States
Facility Name
Novartis Investigative Site
City
Modena
State/Province
MO
ZIP/Postal Code
41100
Country
Italy
12. IPD Sharing Statement
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Safety and Efficacy of RLX030 in Pregnant Women With Pre- Eclampsia
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