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

This study has been terminated.
(Novartis terminated this study due to internal, strategic decisions.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01566630
First received: March 27, 2012
Last updated: October 12, 2015
Last verified: October 2015
  Purpose
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.

Condition Intervention Phase
Pre-eclampsia
Drug: Placebo
Drug: RLX030
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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) [ 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) ] [ Designated as safety issue: Yes ]
    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) [ 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) ] [ Designated as safety issue: Yes ]
    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) [ 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) ] [ Designated as safety issue: Yes ]
    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) [ 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) ] [ Designated as safety issue: Yes ]
    Blood flow to the fetus was monitored using via a Doppler.

  • 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) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: From randomization until 4-6 weeks post partum (maximum 8 weeks) ] [ Designated as safety issue: No ]
  • Rate of Spontaneous Delivery and/or Mode of Delivery [ Time Frame: From randomization to delivery (maximum of 3 weeks) ] [ Designated as safety issue: No ]
  • Number of Patients With Absence of Anti-serelaxin Antibodies [ Time Frame: From Randomization until 4-6 weeks post partum (maximum of 8 weeks) ] [ Designated as safety issue: Yes ]
  • 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 ) ] [ Designated as safety issue: Yes ]
  • Number of Patients With Abnormalities in Fetal Cardiotocography and Biophysical Profile [ Time Frame: Randomization to delivery (maximum of 3 weeks) ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1 ] [ Designated as safety issue: No ]
    Blood concentrations of RLX-030 was assayed to determine this PK parameter.

  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Blood concentrations of RLX-030 was assayed to determine this PK parameter.


Secondary Outcome Measures:
  • Mean Number of Days Before Delivery [ Time Frame: From randomization until delivery (maximum of 3 weeks) ] [ Designated as safety issue: Yes ]

Enrollment: 3
Study Start Date: May 2013
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: RLX030
RLX030 1 mg/mL vials
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

Drug: Placebo
Placebo to RLX030 as intravenous infusion for 72 hours

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01566630

Locations
United States, Alabama
Novartis Investigative Site
Mobile, Alabama, United States, 36604
United States, Kentucky
Novartis Investigative Site
Lexington, Kentucky, United States, 40503
Novartis Investigative Site
Louisville, Kentucky, United States, 40202
United States, Texas
Novartis Investigative Site
Galveston, Texas, United States, 77555-0587
Italy
Novartis Investigative Site
Modena, MO, Italy, 41100
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01566630     History of Changes
Other Study ID Numbers: CRLX030A2205  2011-001617-14 
Study First Received: March 27, 2012
Results First Received: August 6, 2015
Last Updated: October 12, 2015
Health Authority: United States: Food and Drug Administration
Germany: Ministry of Health
Italy: Ministry of Health

Keywords provided by Novartis:
human recombinant RLX030
Pre-eclampsia
hemodynamics
Pharmacokinetics

Additional relevant MeSH terms:
Eclampsia
Pre-Eclampsia
Hypertension, Pregnancy-Induced
Pregnancy Complications

ClinicalTrials.gov processed this record on July 28, 2016