- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01566630
Safety and Efficacy of RLX030 in Pregnant Women With Pre- Eclampsia
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 Overview
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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MO
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Modena, MO, Italy, 41100
- Novartis Investigative Site
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Alabama
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Mobile, Alabama, United States, 36604
- Novartis Investigative Site
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Kentucky
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Lexington, Kentucky, United States, 40503
- Novartis Investigative Site
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Louisville, Kentucky, United States, 40202
- Novartis Investigative Site
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Texas
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Galveston, Texas, United States, 77555-0587
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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. |
RLX030 1 mg/mL vials
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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 |
Placebo to RLX030 as intravenous infusion for 72 hours
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
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Safety and tolerability was assessed by adverse events/serious adverse event and death monitoring.
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Prior to delivery until 4-6 weeks post partum (maximum of 8 weeks)
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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)
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Maternal safety assessment to monitor pre-eclampsia by checking blood pressure during 72 hour treatment period as well as post-dose.
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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)
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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)
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Maternal safety assessment to monitor pre-eclampsia by checking mean arterial pressure during 72 hour treatment period as well as post-dose.
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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)
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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)
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Pre-eclampsia was monitored by checking levels of protein in urine and by urinary protein/creatinine ratio (UPCR)
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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)
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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)
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Blood flow to the fetus was monitored using via a Doppler.
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During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)
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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)
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Heart rate of fetus was monitored continuously throughout 72 hour treatment period using a cardiotocograph.
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During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)
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Improvement in Renal Function Assessed by Increase in Creatinine Clearance
Time Frame: From randomization until 4-6 weeks post partum (maximum 8 weeks)
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From randomization until 4-6 weeks post partum (maximum 8 weeks)
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Rate of Spontaneous Delivery and/or Mode of Delivery
Time Frame: From randomization to delivery (maximum of 3 weeks)
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From randomization to delivery (maximum of 3 weeks)
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Number of Patients With Absence of Anti-serelaxin Antibodies
Time Frame: From Randomization until 4-6 weeks post partum (maximum of 8 weeks)
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From Randomization until 4-6 weeks post partum (maximum of 8 weeks)
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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 )
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up to 4 - 6 weeks post partum (maximum of 8 weeks )
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Number of Patients With Abnormalities in Fetal Cardiotocography and Biophysical Profile
Time Frame: Randomization to delivery (maximum of 3 weeks)
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Randomization to delivery (maximum of 3 weeks)
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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
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Blood concentrations of RLX-030 was assayed to determine this PK parameter.
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Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
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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
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Blood concentrations of RLX-030 was assayed to determine this PK parameter.
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Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
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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
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Blood concentrations of RLX-030 was assayed to determine this PK parameter.
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Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
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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
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Blood concentrations of RLX-030 was assayed to determine this PK parameter.
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Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
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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
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Blood concentrations of RLX-030 was assayed to determine this PK parameter.
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Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Mean Number of Days Before Delivery
Time Frame: From randomization until delivery (maximum of 3 weeks)
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From randomization until delivery (maximum of 3 weeks)
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CRLX030A2205
- 2011-001617-14 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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