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

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

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 4-6weeks post partum ] [ Designated as safety issue: Yes ]
Safety and tolerability will be 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 ] [ 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 ] [ 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 ] [ Designated as safety issue: Yes ]
Pre-eclampsia will also be 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 during delivery in part 1 ] [ Designated as safety issue: Yes ]
Blood flow to the fetus will be 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 during delivery in part 1 ] [ Designated as safety issue: Yes ]
Heart rate of fetus will be monitored continuously throughout 72 hour treatment period using a cardiotocographer.
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 will be assayed to determine AUCinf (if appropriate)
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 will be assayed to determine AUClast (if appropriate)
Pharmacokinetics of RLX030: blood concentration at 24 hour (C 0-24h) after administration- Part 1 [ Time Frame: 24 hours after initiation of infusion during part 1 ] [ Designated as safety issue: No ]
blood concentrations of RLX-030 will be assayed to determine C 0-24h (if appropriate).
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 will be obtained.
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 will be assayed to determine MRT (if appropriate)

Estimated Enrollment:	60
Study Start Date:	April 2013
Estimated Study Completion Date:	September 2015
Estimated Primary Completion Date:	September 2015 (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

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
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

Women that are 28- 33 weeks (+4 days) pregnant with a diagnosis of pre- eclampsia or superimposed pre-eclampsia requiring hospitalization
Fetus deemed in reasonably good health

Exclusion criteria:

Severe hypertension and /or those receiving anti-hypertensive treatment at time of enrollment
Severe headaches, visual changes, or altered mentation
Upper abdominal pain, nausea, or vomiting
Low blood platelet count
Diagnosis of a seizure disorder that requires chronic medication
Those receiving active anti-coagulation therapy
Pre-gestational diabetes (Type 1 or Type 2)
Allergy to magnesium sulfate or steroids
Known major fetal anomaly
Multifetal gestation

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

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

Contacts

Contact: Novartis Pharmaceuticals	1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations

United States, Alabama
Novartis Investigative Site	Not yet recruiting
Mobile, Alabama, United States, 36604
United States, Florida
Novartis Investigative Site	Not yet recruiting
Gainesville, Florida, United States, 32610
United States, Kentucky
Novartis Investigative Site	Not yet recruiting
Lexington, Kentucky, United States, 40503
United States, South Carolina
Novartis Investigative Site	Not yet recruiting
Charleston, South Carolina, United States, 29425
United States, Texas
Novartis Investigative Site	Not yet recruiting
Galveston, Texas, United States, 77555-0587
Novartis Investigative Site	Not yet recruiting
Houston, Texas, United States, 77030
Germany
Novartis Investigative Site	Not yet recruiting
Berlin, Germany, 13353
Novartis Investigative Site	Not yet recruiting
Leipzig, Germany, 04103
Italy
Novartis Investigative Site	Not yet recruiting
Brescia, BS, Italy, 25123
Novartis Investigative Site	Not yet recruiting
Modena, MO, Italy, 41100

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01566630 History of Changes
Other Study ID Numbers:	CRLX030A2205, 2011-001617-14
Study First Received:	March 27, 2012
Last Updated:	March 26, 2013
Health Authority:	United States: Food and Drug Administration France: Ministry of Health Germany: Ministry of Health Italy: Ministry of Health South Africa: Department 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 May 22, 2013