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

Pre-eclampsia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01566630
• Other study ID #: CRLX030A2205
• Secondary ID: 2011-001617-14
• Status: Terminated
• Phase: Phase 2
• First received: March 27, 2012
• Last updated: October 12, 2015
• Start date: May 2013
• Est. completion date: August 2014

Study information

• Verified date: October 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Ministry of HealthItaly: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Eclampsia
• Pre-Eclampsia

Intervention

Drug:
• Placebo
Placebo to RLX030 as intravenous infusion for 72 hours
• RLX030
RLX030 1 mg/mL vials

Locations

Country	Name	City	State
Italy	Novartis Investigative Site	Modena	MO
United States	Novartis Investigative Site	Galveston	Texas
United States	Novartis Investigative Site	Lexington	Kentucky
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	Mobile	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Prior to delivery until 4-6 weeks post partum (maximum of 8 weeks)	Yes
Primary	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.	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)	Yes
Primary	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.	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)	Yes
Primary	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)	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)	Yes
Primary	Decrease in Utero-placental Blood Flow (Part 1)	Blood flow to the fetus was monitored using via a Doppler.	During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)	Yes
Primary	Change in Fetal Heart Rate (Part 1)	Heart rate of fetus was monitored continuously throughout 72 hour treatment period using a cardiotocograph.	During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)	Yes
Primary	Improvement in Renal Function Assessed by Increase in Creatinine Clearance		From randomization until 4-6 weeks post partum (maximum 8 weeks)	No
Primary	Rate of Spontaneous Delivery and/or Mode of Delivery		From randomization to delivery (maximum of 3 weeks)	No
Primary	Number of Patients With Absence of Anti-serelaxin Antibodies		From Randomization until 4-6 weeks post partum (maximum of 8 weeks)	Yes
Primary	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 )	Yes
Primary	Number of Patients With Abnormalities in Fetal Cardiotocography and Biophysical Profile		Randomization to delivery (maximum of 3 weeks)	Yes
Primary	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.	Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1	No
Primary	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.	Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1	No
Primary	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.	Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1	No
Primary	Pharmacokinetics of RLX030: Terminal Elimination Half-life (T1/2)- Part 1	Blood concentrations of RLX-030 was assayed to determine this PK parameter.	Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1	No
Primary	Pharmacokinetics of RLX030: Mean Residence Time (MRT)	Blood concentrations of RLX-030 was assayed to determine this PK parameter.	Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1	No
Secondary	Mean Number of Days Before Delivery		From randomization until delivery (maximum of 3 weeks)	Yes