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Clinical Trial Results:
An adaptive multicenter, randomized, partially double-blind, placebo-controlled study to assess the safety, PK and PD/efficacy of serelaxin in women with pre-eclampsia

Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.

Summary
EudraCT number	2011-001617-14
Trial protocol	DE IT
Global end of trial date	13 Aug 2014

Results information
Results version number	v1(current)
This version publication date	04 May 2016
First version publication date	04 May 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CRLX030A2205

ISRCTN number

US NCT number

NCT01566630

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

CH-4002, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

13 Aug 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

13 Aug 2014

Was the trial ended prematurely?

Yes

Main objective of the trial

Primary Objective: •To assess maternal, fetal, and neonatal safety and tolerability of serelaxin at three doses compared to placebo by assessing effects -on maternal and fetal hemodynamics including systolic blood pressure (SBP) and diastolic blood pressure (DBP), mean arterial pressure (maternal), utero-placental blood flow, and fetal heart rate -on maternal proteinuria and renal function -on rate of spontaneous delivery and/or mode of delivery. -on adverse maternal outcomes -on fetal cardiotocography and biophysical profile -on birth weight, gestational age, Appearance, Pulse, Grimace, Activity, Respiration (APGAR) score, umbilical cord gases, and days in neonatal intensive care unit (NICU) -on adverse fetal/neonatal outcomes -on safety and tolerability during postpartum follow up (4-6 weeks) •To investigate PK and development of anti-drug antibodies (maternal/neonatal) after serelaxin and placebo when administered as iv infusion for 72 hours.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial. In case of severe hypertension (SBP ≥ 160mmHg, DBP ≥ 110 mmHg) anti-hypertensives in accordance with standard practice at the study sites could be used to control blood pressure.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 May 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Italy: 1

Country: Number of subjects enrolled

United States: 2

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

The study was terminated with data available for only three patients.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst, Assessor

Are arms mutually exclusive

Yes

RLX030

Arm description

Because premature termination of the study, only Cohort 1 part 1 had patients with early onset pre-eclampsia. As per planned treatment assigned, patients in this arm received open label serelaxin (RLX030) 15 μg/kg/day i.v. for 72 hours.

Arm type

Experimental

Investigational medicinal product name

Serelaxin

Investigational medicinal product code

RLX030

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

15 μg/kg/day administered intravenously (iv) as infusion for 72 hours to women with pre-eclampsia

Placebo

Arm description

Because premature termination of the study, only Cohort 1 part 1 had patients with early onset pre-eclampsia. The randomized patient received matching placebo of serelaxin (RLX030) in a blinded manner.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

matching placebo to RLX030 administered intravenously (iv) as infusion for 72 hours to women with pre-eclampsia

Number of subjects in period 1	RLX030	Placebo
Started	2	1
Completed	2	1

Baseline characteristics

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Reporting group title

RLX030

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group values	RLX030	Placebo	Total
Number of subjects	2	1	3
Age categorical
Units: Subjects
Adults (18-64 years)	2	1	3
Gender, Male/Female
Units: Participants
Female	2	1	3
Male	0	0	0

End points

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Reporting group title

RLX030

Reporting group description

Reporting group title

Placebo

Reporting group description

Subject analysis set title

RLX030 - Maternal

Subject analysis set type

Safety analysis

Subject analysis set description

Because premature termination of the study, only Cohort 1 part 1 had patients with early onset pre-eclampsia. Serelaxin (RLX030) 15 μg/kg/day i.v. for 72 hours received by pregnant patients with early onset pre-eclampsia

Subject analysis set title

Placebo - Maternal

Subject analysis set type

Safety analysis

Subject analysis set description

Because premature termination of the study, only Cohort 1 part 1 had patients with early onset pre-eclampsia. Matching placebo to serelaxin (RLX030) received for 72 hours by pregnant patients with early onset pre-eclampsia

Subject analysis set title

RLX030- Neonates born to patients

Subject analysis set type

Safety analysis

Subject analysis set description

Neonates born to patients who received Serelaxin (RLX030) 15 μg/kg/day i.v. for 72 hours received

Subject analysis set title

Placebo- Neonates born to patients

Subject analysis set type

Safety analysis

Subject analysis set description

Neonates born to patients who received placebo for 72 hours received by pregnant patients with early onset pre-eclampsia

Primary: Number of patients with adverse events, serious adverse and death during part 1 of the study

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End point title

Number of patients with adverse events, serious adverse and death during part 1 of the study ^[1]

End point description

Safety and tolerability was assessed by adverse events/serious adverse event and death monitoring.

End point type

Primary

End point timeframe

Prior to delivery until 4-6 weeks post partum (maximum of 8 weeks)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal	RLX030- Neonates born to patients	Placebo- Neonates born to patients
Number of subjects analysed	2	1	2	1
Units: Participants
Serious Adverse events	2	1	2	1
Death	0	0	0	0
Non-serious AEs	2	1	2	0

No statistical analyses for this end point

Primary: Change from baseline in maternal systolic blood pressure (SBP) and diastolic blood pressure (DBP) in part 1of the study (part 1)

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End point title

Change from baseline in maternal systolic blood pressure (SBP) and diastolic blood pressure (DBP) in part 1of the study (part 1) ^[2]

End point description

Maternal safety assessment to monitor pre-eclampsia by checking blood pressure during 72 hour treatment period as well as post-dose.

End point type

Primary

End point 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)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal
Number of subjects analysed	0 ^[3]	0 ^[4]
Units: mmHg
least squares mean (standard error)	±	±

Notes
[3] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[4] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Primary: Change from baseline in mean maternal arterial pressure (part 1)

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End point title

Change from baseline in mean maternal arterial pressure (part 1) ^[5]

End point description

Maternal safety assessment to monitor pre-eclampsia by checking mean arterial pressure during 72 hour treatment period as well as post-dose.

End point type

Primary

End point 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)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal
Number of subjects analysed	0 ^[6]	0 ^[7]
Units: mmHg
arithmetic mean (standard deviation)	±	±

Notes
[6] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[7] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Primary: Change from baseline on maternal proteinuria (Part 1)

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End point title

Change from baseline on maternal proteinuria (Part 1) ^[8]

End point description

Pre-eclampsia was monitored by checking levels of protein in urine and by urinary protein/creatinine ratio (UPCR)

End point type

Primary

End point 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)

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal
Number of subjects analysed	0 ^[9]	0 ^[10]
Units: g/24hr
arithmetic mean (standard deviation)	±	±

Notes
[9] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[10] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Primary: Decrease in utero-placental blood flow (Part 1)

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End point title

Decrease in utero-placental blood flow (Part 1) ^[11]

End point description

Blood flow to the fetus was monitored using via a Doppler.

End point type

Primary

End point timeframe

During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal
Number of subjects analysed	0 ^[12]	0 ^[13]
Units: Percentage
number (not applicable)

Notes
[12] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[13] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Primary: Change in fetal heart rate (Part 1)

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End point title

Change in fetal heart rate (Part 1) ^[14]

End point description

Heart rate of fetus was monitored continuously throughout 72 hour treatment period using a cardiotocograph.

End point type

Primary

End point timeframe

During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)

Notes
[14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030- Neonates born to patients	Placebo- Neonates born to patients
Number of subjects analysed	0 ^[15]	0 ^[16]
Units: BPM
arithmetic mean (standard deviation)	±	±

Notes
[15] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[16] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Primary: Improvement in renal function assessed by increase in creatinine clearance

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End point title

Improvement in renal function assessed by increase in creatinine clearance ^[17]

End point description

End point type

Primary

End point timeframe

From randomization until 4-6 weeks post partum (maximum 8 weeks)

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal
Number of subjects analysed	0 ^[18]	0 ^[19]
Units: mL/min/1.73m^2

Notes
[18] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[19] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Primary: Rate of spontaneous delivery and/or mode of delivery

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End point title

Rate of spontaneous delivery and/or mode of delivery ^[20]

End point description

End point type

Primary

End point timeframe

From randomization to delivery (maximum of 3 weeks)

Notes
[20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal
Number of subjects analysed	0 ^[21]	0 ^[22]
Units: Rate
number (not applicable)

Notes
[21] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[22] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

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)

Top of page

End point title

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) ^[23]

End point description

End point type

Primary

End point timeframe

up to 4 - 6 weeks post partum (maximum of 8 weeks )

Notes
[23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030- Neonates born to patients	Placebo- Neonates born to patients
Number of subjects analysed	0 ^[24]	0 ^[25]
Units: Participants
number (not applicable)

Notes
[24] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[25] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Primary: Number of patients with abnormalities in fetal cardiotocography and biophysical profile

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End point title

Number of patients with abnormalities in fetal cardiotocography and biophysical profile ^[26]

End point description

End point type

Primary

End point timeframe

Randomization to delivery (maximum of 3 weeks)

Notes
[26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030- Neonates born to patients	Placebo- Neonates born to patients
Number of subjects analysed	0 ^[27]	0 ^[28]
Units: Participants
number (not applicable)

Notes
[27] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[28] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Primary: Pharmacokinetics of RLX030: area under the blood concentration-time curve from time zero to infinity (AUCinf)-Part 1

Top of page

End point title

Pharmacokinetics of RLX030: area under the blood concentration-time curve from time zero to infinity (AUCinf)-Part 1 ^[29]

End point description

Blood concentrations of RLX-030 was assayed to determine this PK parameter.

End point type

Primary

End point timeframe

Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1

Notes
[29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal	RLX030- Neonates born to patients	Placebo- Neonates born to patients
Number of subjects analysed	0 ^[30]	0 ^[31]	0 ^[32]	0 ^[33]
Units: ng*hr/mL

Notes
[30] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[31] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[32] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[33] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

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

Top of page

End point title

Pharmacokinetics of RLX030: area under the blood concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)-Part 1 ^[34]

End point description

Blood concentrations of RLX-030 was assayed to determine this PK parameter.

End point type

Primary

End point timeframe

Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1

Notes
[34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal	RLX030- Neonates born to patients	Placebo- Neonates born to patients
Number of subjects analysed	0 ^[35]	0 ^[36]	0 ^[37]	0 ^[38]
Units: ng*hr/mL

Notes
[35] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[36] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[37] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[38] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Primary: Pharmacokinetics of RLX030: blood concentration at 24 hour (C 0-24h) after administration- Part 1

Top of page

End point title

Pharmacokinetics of RLX030: blood concentration at 24 hour (C 0-24h) after administration- Part 1 ^[39]

End point description

Blood concentrations of RLX-030 was assayed to determine this PK parameter.

End point type

Primary

End point timeframe

Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1

Notes
[39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal	RLX030- Neonates born to patients	Placebo- Neonates born to patients
Number of subjects analysed	0 ^[40]	0 ^[41]	0 ^[42]	0 ^[43]
Units: ng/mL

Notes
[40] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[41] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[42] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[43] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Primary: Pharmacokinetics of RLX030: terminal elimination half-life (T1/2)- Part 1

Top of page

End point title

Pharmacokinetics of RLX030: terminal elimination half-life (T1/2)- Part 1 ^[44]

End point description

Blood concentrations of RLX-030 was assayed to determine this PK parameter.

End point type

Primary

End point timeframe

Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1

Notes
[44] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal	RLX030- Neonates born to patients	Placebo- Neonates born to patients
Number of subjects analysed	0 ^[45]	0 ^[46]	0 ^[47]	0 ^[48]
Units: Hours

Notes
[45] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[46] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[47] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[48] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Primary: Pharmacokinetics of RLX030: mean residence time (MRT)

Top of page

End point title

Pharmacokinetics of RLX030: mean residence time (MRT) ^[49]

End point description

Blood concentrations of RLX-030 was assayed to determine this PK parameter.

End point type

Primary

End point timeframe

Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1

Notes
[49] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal	RLX030- Neonates born to patients	Placebo- Neonates born to patients
Number of subjects analysed	0 ^[50]	0 ^[51]	0 ^[52]	0 ^[53]
Units: Hours

Notes
[50] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[51] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[52] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[53] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Primary: Number of Patients With Absence of Anti-serelaxin Antibodies

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End point title

Number of Patients With Absence of Anti-serelaxin Antibodies ^[54]

End point description

End point type

Primary

End point timeframe

From Randomization until 4-6 weeks post partum (maximum of 8 weeks)

Notes
[54] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal analysis was performed as the study was terminated after three patients were enrolled and dosed

End point values	RLX030 - Maternal	Placebo - Maternal	RLX030- Neonates born to patients	Placebo- Neonates born to patients
Number of subjects analysed	0 ^[55]	0 ^[56]	0 ^[57]	0 ^[58]
Units: Patients

Notes
[55] - No formal analysis was performed as the study was terminated after three patients were enrolled and
[56] - No formal analysis was performed as the study was terminated after three patients were enrolled and
[57] - No formal analysis was performed as the study was terminated after three patients were enrolled and
[58] - No formal analysis was performed as the study was terminated after three patients were enrolled and

No statistical analyses for this end point

Secondary: Mean number of days before delivery

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End point title

Mean number of days before delivery

End point description

End point type

Secondary

End point timeframe

From randomization until delivery (maximum of 3 weeks)

End point values	RLX030 - Maternal	Placebo - Maternal
Number of subjects analysed	0 ^[59]	0 ^[60]
Units: Days

Notes
[59] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed
[60] - No formal analysis was performed as study was terminated after three pts were enrolled and dosed

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

RLX030 - Maternal

Reporting group description

Because premature termination of the study, only Cohort 1 part 1 had patients with early onset preeclampsia. Serelaxin (RLX030) 15 μg/kg/day i.v. for 72 hours received by pregnant patients with early onset pre-eclampsia

Reporting group title

RLX030 - Neonates Born to Patients

Reporting group description

Neonates born to patients who received Serelaxin (RLX030) 15 μg/kg/day i.v. for 72 hours received

Reporting group title

Placebo - Maternal

Reporting group description

Because premature termination of the study, only Cohort 1 part 1 had patients with early onset preeclampsia. Matching placebo to serelaxin (RLX030) received for 72 hours by pregnant patients with early onset pre-eclampsia

Reporting group title

Placebo - Neonates Born to Patients

Reporting group description

Neonates born to patients who received placebo for 72 hours received by pregnant patients with early onset pre-eclampsia

Serious adverse events	RLX030 - Maternal	RLX030 - Neonates Born to Patients	Placebo - Maternal	Placebo - Neonates Born to Patients
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 2 (100.00%)	2 / 2 (100.00%)	1 / 1 (100.00%)	1 / 1 (100.00%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Vascular disorders
Hypertension
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Caesarean section
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Pre-eclampsia
subjects affected / exposed	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Premature baby
subjects affected / exposed	0 / 2 (0.00%)	2 / 2 (100.00%)	0 / 1 (0.00%)	1 / 1 (100.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Premature delivery
subjects affected / exposed	2 / 2 (100.00%)	0 / 2 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	RLX030 - Maternal	RLX030 - Neonates Born to Patients	Placebo - Maternal	Placebo - Neonates Born to Patients
Total subjects affected by non serious adverse events
subjects affected / exposed	2 / 2 (100.00%)	2 / 2 (100.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0
Blood creatinine increased
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0
Platelet count decreased
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	2	0	0	0
Surgical and medical procedures
Mechanical ventilation
subjects affected / exposed	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0
Nervous system disorders
Headache
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	3	0	0	0
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0
Gastrointestinal disorders
Constipation
subjects affected / exposed	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0
Nausea
subjects affected / exposed	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0
Vomiting
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)
occurrences all number	1	0	1	0
Hepatobiliary disorders
Jaundice
subjects affected / exposed	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
subjects affected / exposed	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0
Apnoea
subjects affected / exposed	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0
Dyspnoea
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0
Epistaxis
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0
Transient tachypnoea of the newborn
subjects affected / exposed	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0
Metabolism and nutrition disorders
Hypoalbuminaemia
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0
Hypoglycaemia
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Novartis terminated this study due to internal, strategic decisions

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Clinical trials

Clinical Trial Results: An adaptive multicenter, randomized, partially double-blind, placebo-controlled study to assess the safety, PK and PD/efficacy of serelaxin in women with pre-eclampsia

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of patients with adverse events, serious adverse and death during part 1 of the study

Primary: Number of patients with adverse events, serious adverse and death during part 1 of the study

Primary: Change from baseline in maternal systolic blood pressure (SBP) and diastolic blood pressure (DBP) in part 1of the study (part 1)

Primary: Change from baseline in maternal systolic blood pressure (SBP) and diastolic blood pressure (DBP) in part 1of the study (part 1)

Primary: Change from baseline in mean maternal arterial pressure (part 1)

Primary: Change from baseline in mean maternal arterial pressure (part 1)

Primary: Change from baseline on maternal proteinuria (Part 1)

Primary: Change from baseline on maternal proteinuria (Part 1)

Primary: Decrease in utero-placental blood flow (Part 1)

Primary: Decrease in utero-placental blood flow (Part 1)

Primary: Change in fetal heart rate (Part 1)

Primary: Change in fetal heart rate (Part 1)

Primary: Improvement in renal function assessed by increase in creatinine clearance

Primary: Improvement in renal function assessed by increase in creatinine clearance

Primary: Rate of spontaneous delivery and/or mode of delivery

Primary: Rate of spontaneous delivery and/or mode of delivery

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)

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)

Primary: Number of patients with abnormalities in fetal cardiotocography and biophysical profile

Primary: Number of patients with abnormalities in fetal cardiotocography and biophysical profile

Primary: Pharmacokinetics of RLX030: area under the blood concentration-time curve from time zero to infinity (AUCinf)-Part 1

Primary: Pharmacokinetics of RLX030: area under the blood concentration-time curve from time zero to infinity (AUCinf)-Part 1

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

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

Primary: Pharmacokinetics of RLX030: blood concentration at 24 hour (C 0-24h) after administration- Part 1

Primary: Pharmacokinetics of RLX030: blood concentration at 24 hour (C 0-24h) after administration- Part 1

Primary: Pharmacokinetics of RLX030: terminal elimination half-life (T1/2)- Part 1

Primary: Pharmacokinetics of RLX030: terminal elimination half-life (T1/2)- Part 1

Primary: Pharmacokinetics of RLX030: mean residence time (MRT)

Primary: Pharmacokinetics of RLX030: mean residence time (MRT)

Primary: Number of Patients With Absence of Anti-serelaxin Antibodies

Primary: Number of Patients With Absence of Anti-serelaxin Antibodies

Secondary: Mean number of days before delivery

Secondary: Mean number of days before delivery

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
An adaptive multicenter, randomized, partially double-blind, placebo-controlled study to assess the safety, PK and PD/efficacy of serelaxin in women with pre-eclampsia