Clinical trial NCT01566630: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pre-eclampsia
Keywords: human recombinant RLX030
Pre-eclampsia
hemodynamics
Pharmacokinetics
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-03-29
Enrollment: 3
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Number of Patients With Adverse Events, Serious Adverse and Death During Part 1 of the Study
timeFrame: Prior to delivery until 4-6 weeks post partum (maximum of 8 weeks)
measure: Change From Baseline in Maternal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Part 1of the Study (Part 1)
timeFrame: 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)
measure: Change From Baseline in Mean Maternal Arterial Pressure (Part 1)
timeFrame: 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)
measure: Change From Baseline on Maternal Proteinuria (Part 1)
timeFrame: 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)
measure: Decrease in Utero-placental Blood Flow (Part 1)
timeFrame: During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)
measure: Change in Fetal Heart Rate (Part 1)
timeFrame: During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)
measure: Improvement in Renal Function Assessed by Increase in Creatinine Clearance
timeFrame: From randomization until 4-6 weeks post partum (maximum 8 weeks)
measure: Rate of Spontaneous Delivery and/or Mode of Delivery
timeFrame: From randomization to delivery (maximum of 3 weeks)
measure: Number of Patients With Absence of Anti-serelaxin Antibodies
timeFrame: From Randomization until 4-6 weeks post partum (maximum of 8 weeks)
measure: 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)
timeFrame: up to 4 - 6 weeks post partum (maximum of 8 weeks )
measure: Number of Patients With Abnormalities in Fetal Cardiotocography and Biophysical Profile
timeFrame: Randomization to delivery (maximum of 3 weeks)
measure: Pharmacokinetics of RLX030: Area Under the Blood Concentration-time Curve From Time Zero to Infinity (AUCinf)-Part 1
timeFrame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
measure: Pharmacokinetics of RLX030: Area Under the Blood Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)-Part 1
timeFrame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
measure: Pharmacokinetics of RLX030: Blood Concentration at 24 Hour (C 0-24h) After Administration- Part 1
timeFrame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
measure: Pharmacokinetics of RLX030: Terminal Elimination Half-life (T1/2)- Part 1
timeFrame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
measure: Pharmacokinetics of RLX030: Mean Residence Time (MRT)
timeFrame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Secondary outcomes:
measure: Mean Number of Days Before Delivery
timeFrame: From randomization until delivery (maximum of 3 weeks)
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Lexington
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Louisville
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Galveston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: