Download PDF

Clinical Trial Results:
A MULTI-CENTRE, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND, TWO-ARMED, PARALLEL GROUP STUDY TO EVALUATE EFFICACY AND SAFETY OF INTRAVENOUS (IV) SILDENAFIL IN THE TREATMENT OF NEONATES WITH PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN (PPHN) OR HYPOXIC RESPIRATORY FAILURE (HRF) AND AT RISK FOR PPHN, WITH A LONG TERM FOLLOW-UP INVESTIGATION OF DEVELOPMENTAL PROGRESS 12 AND 24 MONTHS AFTER COMPLETION OF STUDY TREATMENT

Summary
EudraCT number	2012-002619-24
Trial protocol	BE GB SE ES AT DE NO IT NL DK FR
Global end of trial date	28 Sep 2020

Results information
Results version number	v2(current)
This version publication date	08 Apr 2021
First version publication date	17 Jul 2019
Other versions	v1
Version creation reason	Correction of full data set Basic Results being posted with final data / end of global study date need to be added to results

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

A1481316

ISRCTN number

US NCT number

NCT01720524

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000671-PIP01-09

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?

Yes

Analysis stage

Final

Date of interim/final analysis

27 Jan 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

17 Oct 2018

Global end of trial reached?

Yes

Global end of trial date

28 Sep 2020

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy and safety of IV sildenafil when added to inhaled nitric oxide (iNO) for the treatment of neonates with PPHN or HRF and at risk for PPHN.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

All subjects were treated with iNO.

Evidence for comparator

Actual start date of recruitment

05 Aug 2013

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

2 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 1

Country: Number of subjects enrolled

Canada: 3

Country: Number of subjects enrolled

Denmark: 4

Country: Number of subjects enrolled

France: 3

Country: Number of subjects enrolled

Germany: 1

Country: Number of subjects enrolled

Netherlands: 5

Country: Number of subjects enrolled

Norway: 1

Country: Number of subjects enrolled

Spain: 4

Country: Number of subjects enrolled

Sweden: 8

Country: Number of subjects enrolled

United Kingdom: 10

Country: Number of subjects enrolled

United States: 19

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

Top of page

Recruitment details

This study was conducted in two parts Part A (double-blind phase) and Part B (long-term, non-interventional phase).

Screening details

Neonates with PPHN or HRF and at risk of PPHN who were receiving iNO treatment were evaluated in this study.

Period 1 title

Part A (Double-blind Phase)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

IV Sildenafil

Arm description

Subjects received sildenafil intravenously based on their body weight at a loading dose of 0.1 milligrams per kg (mg/kg) for 30 minutes on Day 1 followed by a maintenance dose of 0.03 milligrams per kg per hour (mg/kg/hr), for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of subjects’ safety and well-being.

Arm type

Experimental

Investigational medicinal product name

Sildenafil Citrate

Investigational medicinal product code

UK-092,480

Other name

Revatio

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

IV sildenafil at a loading dose of 0.1 mg/kg, for 30 minutes, on Day 1, followed by maintenance dose of 0.03 mg/kg/hr, for a minimum of 2 days and maximum of 14 days.

Placebo

Arm description

Subjects received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on subject’s weight for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of subjects’ safety and well-being.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Placebo (0.9 percent [%] normal saline or dextrose 10%) intravenously for a minimum of 2 days and maximum of 14 days.

Number of subjects in period 1	IV Sildenafil	Placebo
Started	29	30
Completed	22	18
Not completed	7	12
Consent withdrawn by subject	-	1
Missed 28 day follow-up visit	1	1
Other	-	1
Adverse event	2	2
Insufficient Clinical Response	2	4
Death (during follow-up)	-	1
Death (not completed study treatment)	2	-
Lost to follow-up	-	1
Protocol deviation	-	1

Period 2 title

Part B (Non-Interventional Phase)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

IV Sildenafil

Arm description

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Placebo

Arm description

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	IV Sildenafil	Placebo
Started	22	18
Completed	22	17
Not completed	5	9
Death	-	2
No longer willing to participate in study	1	4
Unspecified	2	-
Lost to follow-up	2	3
Joined	5	8
Continued to follow-up	5	8

Baseline characteristics

Top of page

Reporting group title

IV Sildenafil

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group values	IV Sildenafil	Placebo	Total
Number of subjects	29	30	59
Age Categorical
Safety population included all subjects treated with study treatment.
Units: Subjects
Newborns (0-27 days)	29	30	59
Age Continuous
Safety population included all subjects treated with study treatment.
Units: days
arithmetic mean (standard deviation)	1.7 ± 0.90	1.9 ± 0.75	-
Gender Categorical
Safety population included all subjects treated with study treatment.
Units: Subjects
Female	13	13	26
Male	16	17	33
Race
Safety population included all subjects treated with study treatment.
Units: Subjects
White	19	16	35
Black	1	7	8
Asian	2	5	7
Other	3	1	4
Unspecified	4	1	5

End points

Top of page

Reporting group title

IV Sildenafil

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group title

IV Sildenafil

Reporting group description

Reporting group title

Placebo

Reporting group description

Subject analysis set title

Part B (Non-Interventional Phase): IV Sildenafil

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Part B (Non-Interventional Phase): Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Subjects Without Treatment Failure

Top of page

End point title

Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Subjects Without Treatment Failure

End point description

Time in days, on iNO treatment, for subjects without iNO treatment failure, was calculated 14 days from the initiation of IV study drug or hospital discharge, whichever occurred first. iNO treatment failure was defined as need for additional treatment targeting PPHN, need for extra corporeal membrane oxygenation (ECMO), or death during the study. The intent-to-treat population (ITT) included all randomized subjects treated with study treatment. Here, “Number of Subjects Analyzed” signifies number of subjects without iNO treatment failure.

End point type

Primary

End point timeframe

14 days from the initiation of IV study drug or hospital discharge, whichever occurs first

End point values	IV Sildenafil	Placebo
Number of subjects analysed	21	24
Units: days
least squares mean (confidence interval 95%)	4.1 (2.58 to 5.58)	4.1 (2.70 to 5.50)

IV Sildenafil vs. Placebo

Statistical analysis description

Field appearing in section: "Number of subjects included in analysis", is an auto populated field from database (sum of number of subjects analyzed for the reporting arms selected to report statistical data): which may not be the actual number of subjects contributing to statistical analysis. Only subjects without treatment failure were included in the analysis.

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.985

Method

ANCOVA

Parameter type

Least square (LS) mean difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.08

upper limit

2.04

Variability estimate

Standard error of the mean

Dispersion value

1.02

Primary: Treatment Failure Rate

Top of page

End point title

Treatment Failure Rate

End point description

Treatment failure rate was defined as percentage of subjects who needed additional treatment targeting PPHN, needed ECMO, or died during the study. The ITT population included all randomized subjects treated with study treatment.

End point type

Primary

End point timeframe

14 days from the initiation of IV study drug or hospital discharge, whichever occurs first

End point values	IV Sildenafil	Placebo
Number of subjects analysed	29	30
Units: percentage of subjects
number (confidence interval 95%)	27.6 (11.3 to 43.9)	20.0 (5.7 to 34.3)

IV Sildenafil vs. Placebo

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4935

Method

Chi-squared

Parameter type

Difference in percentage

Point estimate

7.6

Confidence interval

level

95%

sides

2-sided

lower limit

-14.1

upper limit

29.3

Secondary: Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation

Top of page

End point title

Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation

End point description

Time in days, from initiation of IV study drug to final weaning of mechanical ventilation among subjects achieving final weaning of mechanical ventilation for PPHN was evaluated. Kaplan-Meier method was used for estimation. For subjects with mechanical ventilation beyond 336 hours (14 days) from initiation of IV study drug, data is censored at 14 days. The ITT population included all randomized subjects treated with study treatment.

End point type

Secondary

End point timeframe

14 days from the initiation of IV study drug or hospital discharge, whichever occurs first

End point values	IV Sildenafil	Placebo
Number of subjects analysed	29	30
Units: days
median (confidence interval 95%)	8.3 (5.46 to 11.75)	7.3 (5.46 to 10.78)

IV Sildenafil vs. Placebo

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9885

Method

Logrank

Confidence interval

Secondary: Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure

Top of page

End point title

Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure

End point description

Time in days, from initiation of IV study drug to first treatment failure (defined as need for additional treatment targeting PPHN, need for ECMO, or death) for subjects with treatment failure was evaluated. Kaplan-Meier method was used for estimation. For subjects without treatment failure by the endpoint assessment date, data is censored at the endpoint assessment date. The ITT population included all randomized subjects treated with study treatment. Due to low number of subjects with events, Kaplan-Meier estimates of median, upper and lower limit of CI could not be estimated/calculated and has been denoted by “99999”, signifying data not available.

End point type

Secondary

End point timeframe

14 days from the initiation of IV study drug or hospital discharge, whichever occurs first

End point values	IV Sildenafil	Placebo
Number of subjects analysed	29	30
Units: days
median (confidence interval 95%)	99999 (-99999 to 99999)	99999 (-99999 to 99999)

IV Sildenafil vs. Placebo

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.491

Method

Logrank

Confidence interval

Secondary: Percentage of Subjects With Individual Components of Treatment Failure

Top of page

End point title

Percentage of Subjects With Individual Components of Treatment Failure

End point description

Percentage of subjects with individual components of treatment failure (need to start additional treatment targeting PPHN, need to start ECMO, or death) were evaluated. Some subjects could have had multiple qualifying events for treatment failure. The ITT population included all randomized subjects treated with study treatment.

End point type

Secondary

End point timeframe

14 days from the initiation of IV study drug or hospital discharge, whichever occurs first

End point values	IV Sildenafil	Placebo
Number of subjects analysed	29	30
Units: percentage of subjects
number (confidence interval 95%)
Additional Treatment Targeting PPHN	13.8 (3.9 to 31.7)	10.0 (2.1 to 26.5)
ECMO	10.3 (2.2 to 27.4)	10.0 (2.1 to 26.5)
Death	6.9 (0.8 to 22.8)	0.0 (0.0 to 11.6)

IV Sildenafil vs. Placebo: Additional Treatment

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7065

Method

Fisher exact

Parameter type

Difference in Percentage

Point estimate

3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-15.2

upper limit

22.9

IV Sildenafil vs. Placebo: ECMO

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

> 0.999

Method

Fisher exact

Parameter type

Difference in Percentage

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-18.5

upper limit

18.5

IV Sildenafil vs. Placebo: Death

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2373

Method

Fisher exact

Parameter type

Difference in Percentage

Point estimate

6.9

Confidence interval

level

95%

sides

2-sided

lower limit

-5.5

upper limit

22.8

Secondary: Change From Baseline in Oxygenation Index (OI) at Hour 6, 12 and 24

Top of page

End point title

Change From Baseline in Oxygenation Index (OI) at Hour 6, 12 and 24

End point description

Oxygenation index was calculated as the product of fraction of inspired oxygen (FiO2) and mean airway pressure divided by partial pressure of oxygen dissolved in arterial blood (PaO2) [(FiO2*mean airway pressure)/PaO2] measured in centimeter of water per millimeter of mercury (cmH2O/mmHg). FiO2 is the measure of oxygen concentration that is breathed. Mean airway pressure is defined as an average of the airway pressure throughout the respiratory cycle. PaO2 is the measure of oxygen level dissolved in the arterial blood. Here, ‘n’ = subjects evaluable for this endpoint at specified time points. The ITT population included all randomized subjects treated with study treatment.

End point type

Secondary

End point timeframe

Baseline, Hour 6, 12 and 24 after start of infusion

End point values	IV Sildenafil	Placebo
Number of subjects analysed	29	30
Units: cmH2O/mmHg
least squares mean (confidence interval 95%)
Change at Hour 6 (n=29,22)	-4.2 (-11.64 to 3.34)	-8.0 (-16.63 to 0.57)
Change at Hour 12 (n=28,22)	-4.1 (-10.51 to 2.23)	-8.2 (-15.42 to -1.04)
Change at Hour 24 (n=18,17)	-11.6 (-15.40 to -7.83)	-9.5 (-13.36 to -5.57)

IV Sildenafil vs. Placebo: Hour 6

Statistical analysis description

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4984

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-7.5

upper limit

15.3

IV Sildenafil vs. Placebo: Hour 12

Statistical analysis description

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3956

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.5

upper limit

13.7

IV Sildenafil vs. Placebo: Hour 24

Statistical analysis description

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4249

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-7.6

upper limit

3.3

Secondary: Change From Baseline in Differential Saturation at Hour 6, 12 and 24

Top of page

End point title

Change From Baseline in Differential Saturation at Hour 6, 12 and 24

End point description

Differential oxygenation saturation is a simple way to detect the right-to-left shunting at ductus arteriosus using 2 pulse oximeters. It is the difference between pre-ductal and post-ductal sites pulse oxygen saturation (SpO2). Where, pre-duct refers to right upper extremity and post-duct refers to lower limb. Oxygenation saturation is measured as percentage of hemoglobin binding sites occupied by oxygen in the blood. Here, ‘n’ = subjects evaluable for this endpoint at specified time points. The ITT population included all randomized subjects treated with study treatment.

End point type

Secondary

End point timeframe

Baseline, Hour 6, 12 and 24 after start of infusion

End point values	IV Sildenafil	Placebo
Number of subjects analysed	29	30
Units: percentage of hemoglobin
least squares mean (confidence interval 95%)
Change at Hour 6 (n=26,19)	1.5 (-1.79 to 4.80)	0.8 (-3.10 to 4.62)
Change at Hour 12 (n=25,19)	-1.2 (-7.65 to 5.21)	6.7 (-0.65 to 14.12)
Change at Hour 24 (n=19,14)	1.2 (-7.15 to 9.49)	9.3 (-0.40 to 19.08)

IV Sildenafil vs. Placebo: Hour 6

Statistical analysis description

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7686

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.3

upper limit

5.8

IV Sildenafil vs. Placebo: Hour 12

Statistical analysis description

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1112

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-8

Confidence interval

level

95%

sides

2-sided

lower limit

-17.8

upper limit

1.9

IV Sildenafil vs. Placebo: Hour 24

Statistical analysis description

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2089

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-8.2

Confidence interval

level

95%

sides

2-sided

lower limit

-21.2

upper limit

4.8

Secondary: Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hour 6, 12 and 24

Top of page

End point title

Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hour 6, 12 and 24

End point description

The ratio of partial pressure of arterial oxygen to fraction of inspired oxygen is a ratio between the oxygen level in the arterial blood and the oxygen concentration that is breathed. It helps to determine the degree of any problems with how the lungs transfer oxygen to the blood. Here, ‘n’ = subjects evaluable for this endpoint at specified time points. The ITT population consisted of all randomized subjects treated with study treatment.

End point type

Secondary

End point timeframe

Baseline, Hour 6, 12 and 24 after start of infusion

End point values	IV Sildenafil	Placebo
Number of subjects analysed	29	30
Units: ratio
least squares mean (confidence interval 95%)
Change at Hour 6 (n=29,23)	45.3 (17.21 to 73.37)	8.1 (-23.48 to 39.60)
Change at Hour 12 (n=28,24)	43.4 (16.76 to 70.13)	16.9 (-11.97 to 45.68)
Change at Hour 24 (n=20,17)	94.6 (18.52 to 170.69)	14.7 (-67.83 to 97.25)

IV Sildenafil vs. Placebo: Hour 6

Statistical analysis description

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0829

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

37.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5

upper limit

79.5

IV Sildenafil vs. Placebo: Hour 12

Statistical analysis description

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1802

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

26.6

Confidence interval

level

95%

sides

2-sided

lower limit

-12.7

upper limit

65.9

IV Sildenafil vs. Placebo: Hour 24

Statistical analysis description

Comparison groups

IV Sildenafil v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1576

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

79.9

Confidence interval

level

95%

sides

2-sided

lower limit

-32.5

upper limit

192.2

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Top of page

End point title

Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

End point description

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent are events between first infusion of study drug and up to 31 days after end of study drug infusion (up to 45 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. The safety population included all subjects treated with study treatment.

End point type

Secondary

End point timeframe

Baseline up to 31 days after end of study drug infusion (up to 45 days)

End point values	IV Sildenafil	Placebo
Number of subjects analysed	29	30
Units: subjects
AEs	22	19
SAEs	7	2

No statistical analyses for this end point

Secondary: Number of Treatment-Emergent Adverse Events (AEs) According to Severity

Top of page

End point title

Number of Treatment-Emergent Adverse Events (AEs) According to Severity

End point description

AE: untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. SAE: AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent are events between first infusion of study drug and up to 31 days after end of study drug infusion (up to 45 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Severity criteria: mild=did not interfere with subject's usual function; moderate=interfered to some extent with subject's usual function and severe=interfered significantly with subject's usual function. Missing baseline severities were imputed as mild. The safety population included all subjects treated with study treatment.

End point type

Secondary

End point timeframe

Baseline up to 31 days after end of study drug infusion (up to 45 days)

End point values	IV Sildenafil	Placebo
Number of subjects analysed	29	30
Units: events
Mild	49	42
Moderate	29	24
Severe	12	17

No statistical analyses for this end point

Secondary: Number of Subjects With Laboratory Abnormalities

Top of page

End point title

Number of Subjects With Laboratory Abnormalities

End point description

Criteria for laboratory values: Hematology: hemoglobin, hematocrit, red blood cell count <0.8*lower limit of normal (LLN), platelets<0.5*LLN, >1.75*upper limit of normal (ULN), white blood cells count <0.6*LLN, >1.5*ULN; Liver function: total and direct bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase >3.0*ULN, total protein <0.8*LLN, >1.2*ULN; Renal function: blood urea nitrogen, creatinine >1.3*ULN; Electrolytes: sodium <0.95*LLN, >1.05*ULN, potassium, chloride, calcium, bicarbonate (venous) <0.9*LLN, >1.1*ULN. Here, “number of subjects analyzed” signifies those subjects who were evaluable for this endpoint. The safety population included all subjects treated with study treatment.

End point type

Secondary

End point timeframe

Up to 14 days from initiation of study drug infusion

End point values	IV Sildenafil	Placebo
Number of subjects analysed	29	28
Units: subjects	27	22

No statistical analyses for this end point

Secondary: Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Subjects as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)

Top of page

End point title

Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Subjects as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)

End point description

Bayley-III assesses infant and toddler development across five domains: cognitive, language, motor, social-emotional (SE), and adaptive behavior (AB). Assessments of the cognitive, language, and motor domains conducted using items administered to the child; assessments of the SE and AB domains conducted using the primary caregiver’s responses to a questionnaire. Score ranges: cognitive scale 0-91, language scale 0-97 and motor scale 0-132, where higher scores indicated better cognitive function, communication and motor skills respectively. Raw scores of cognitive, language and motor domains were converted to composite scores. Composite scores of cognitive, language and motor developmental scales ranged from a scale of 40 to 160, where higher score indicated stronger skills and abilities. Part-B safety analysis set. Number Analysed =subjects evaluable for this end point, n =subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	19	13
Units: units on a scale
arithmetic mean (standard deviation)
Cognitive Development: Month 12 (n =19, 12)	97.5 ± 16.14	94.5 ± 14.18
Cognitive Development: Month 24 (n =17, 13)	97.4 ± 18.12	97.3 ± 14.95
Language Development: Month 12 (n =18, 12)	99.5 ± 16.86	94.7 ± 10.25
Language Development: Month 24 (n =16, 11)	96.7 ± 21.91	95.8 ± 17.70
Motor Development: Month 12 (n =19, 12)	93.1 ± 16.10	88.2 ± 14.61
Motor Development: Month 24 (n =17, 12)	99.0 ± 19.59	105.3 ± 24.00

No statistical analyses for this end point

Secondary: Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire of Subjects as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)

Top of page

End point title

Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire of Subjects as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)

End point description

The Bayley-III assesses infant and toddler development across five domains: cognitive, language, motor, social-emotional (SE), and adaptive behavior (AB). Assessments of the cognitive, language, and motor domains conducted using items administered to the child; assessments of the SE and AB domains conducted using the primary caregiver’s responses to a questionnaire. The questionnaire comprises the SE scale (35 items) and the AB scale (241 items). Raw scores of SE and AB were converted to composite scores. Composite scores for SE and AB scale ranged from 40 to 160, where higher scores indicated better social-emotional skills and adaptive behavior in child. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. 'Number Analysed' = subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Month 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	15	8
Units: units on a scale
arithmetic mean (standard deviation)
Social-Emotional Development	104.5 ± 21.40	112.5 ± 18.13
Adaptive Behavior Development	91.6 ± 15.66	98.3 ± 12.44

No statistical analyses for this end point

Secondary: Part B: Number of Subjects With Eye Movement Disorders as Assessed by Eye Examination

Top of page

End point title

Part B: Number of Subjects With Eye Movement Disorders as Assessed by Eye Examination

End point description

Standard age-appropriate ophthalmological examinations of subjects were used to assess eye movement disorders (presence of amblyopia, strabismus, and nystagmus) at month 12 and 24. In this end point, data have been reported for right and left eye separately. Rows according to eye movement disorder categories at specified time points are reported in this end point, only when there was a non-zero data for at least 1 reporting arm. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Number of Subjects Analysed' signifies number of subjects evaluable for this end point and ‘n’ signifies number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	16	14
Units: subjects
Strabismus Present,Right Eye: Month 12 (n =16, 14)	0	1
Strabismus Present,Left Eye: Month 12 (n =16, 14)	0	1
Strabismus Present,Right Eye: Month 24 (n =12, 12)	1	0
Strabismus Present,Left Eye: Month 24 (n =12, 12)	1	0
Nystagmus Present,Left Eye: Month 24 (n =12, 12)	0	1

No statistical analyses for this end point

Secondary: Part B: Visual Acuity of Verbal Subjects as Assessed by Ophthalmological Assessment

Top of page

End point title

Part B: Visual Acuity of Verbal Subjects as Assessed by Ophthalmological Assessment

End point description

Standard age-appropriate ophthalmological examinations were used to assess visual acuity (performed differently for children able of verbal interaction) through visual acuity chart (VAC) quantitative, counting finger (CF), hand motion (HM), light perception (LP), no light perception (NLP) and missing at month 12 and 24. In this end point, data have been reported for right and left eye separately. Rows according to visual acuity categories at specified time points are reported in this end point, only when there was a non-zero data for at least 1 reporting arm. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Number of Subjects Analysed' signifies number of subjects evaluable for this end point and ‘n’ signifies number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	16	14
Units: subjects
VAC Quantitative, Right Eye: Month 12 (n =16, 14)	2	1
HM, Right Eye: Month 12 (n =16, 14)	0	2
LP, Right Eye: Month 12 (n =16, 14)	1	0
Missing, Right Eye: Month 12 (n =16, 14)	13	11
VAC Quantitative, Left Eye: Month 12 (n =16, 14)	2	1
HM, Left Eye: Month 12 (n =16, 14)	0	2
LP, Left Eye: Month 12 (n =16, 14)	1	0
Missing, Left Eye: Month 12 (n =16, 14)	13	11
VAC Quantitative, Right Eye: Month 24 (n =12, 12)	6	5
HM, Right Eye: Month 24 (n =12, 12)	1	0
Missing, Right Eye: Month 24 (n =12, 12)	5	7
VAC Quantitative, Left Eye: Month 24 (n =12, 12)	6	5
Missing, Left Eye: Month 24 (n =12, 12)	6	7

No statistical analyses for this end point

Secondary: Part B: Visual Acuity of Non-Verbal Subjects as Assessed by Ophthalmological Assessment

Top of page

End point title

Part B: Visual Acuity of Non-Verbal Subjects as Assessed by Ophthalmological Assessment

End point description

Standard age-appropriate ophthalmological examinations were used to assess visual acuity (performed differently for children unable of verbal interaction) through fixates and follows [F&F] (included central, steady and maintained), light perception [LP] (wince to light), no light perception [NLP], and missing at month 12 and 24. In this end point, data have been reported for right and left eye separately. Rows according to visual acuity categories at specified time points are reported in this end point, only when there was a non-zero data for at least 1 reporting arm. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Number of Subjects Analysed' signifies number of subjects evaluable for this end point and ‘n’ signifies number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	16	14
Units: subjects
F&F, Right Eye: Month 12 (n =16, 14)	15	13
LP, Right Eye: Month 12 (n =16, 14)	0	1
Missing, Right Eye: Month 12 (n =16, 14)	1	0
F&F, Left Eye: Month 12 (n =16, 14)	15	13
LP, Left Eye: Month 12 (n =16, 14)	0	1
Missing, Left Eye: Month 12 (n =16, 14)	1	0
F&F, Right Eye: Month 24 (n =12, 12)	5	9
Missing, Right Eye: Month 24 (n =12, 12)	7	3
F&F, Left Eye: Month 24 (n =12, 12)	5	9
Missing, Left Eye: Month 24 (n =12, 12)	7	3

No statistical analyses for this end point

Secondary: Part B: Visual Acuity of Verbal Subjects as Assessed by LogMAR Through Visual Acuity Chart

Top of page

End point title

Part B: Visual Acuity of Verbal Subjects as Assessed by LogMAR Through Visual Acuity Chart

End point description

Standard age-appropriate ophthalmological examinations were used to assess visual acuity (performed differently for children able of verbal interaction) at month 12 and 24. Visual acuity (VA) of verbal children was assessed for each eye using the Snellen method, where logarithm of minimum angle of resolution (logMAR) units were derived from the Snellen ratios. Subjects had to read letters from the chart at a distance of 20 feet/6 meter or 4 meter. VA (Snellen ratio) = distance between the chart and subject, divided by distance at which subject was able to see/read chart without impairment; expressed as decimal, logMAR = log10 (1/decimal VA). In this end point, data have been reported for right and left eye separately. Part B safety analysis. Here 'Number of Subjects Analysed' signifies number of subjects evaluable for this end point and ‘n’ signifies number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	6	6
Units: LogMAR
arithmetic mean (standard deviation)
Right Eye: Month 12 (n =6, 3)	0.45 ± 0.394	0.57 ± 0.513
Left Eye: Month 12 (n =6, 3)	0.47 ± 0.372	0.57 ± 0.513
Right Eye: Month 24 (n =6, 4)	0.20 ± 0.155	0.28 ± 0.299
Left Eye: Month 24 (n =6, 6)	0.20 ± 0.155	0.35 ± 0.409

No statistical analyses for this end point

Secondary: Part B: Visual Status of Subjects With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments

Top of page

End point title

Part B: Visual Status of Subjects With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments

End point description

Standard age-appropriate ophthalmological examinations were used to assess examination of anterior and posterior chamber for abnormality in lids, conjunctiva, cornea, anterior chamber, lens, iris, pupil, extraocular muscle movement (EMM) and eye movements at month 12 and 24. In this end point, data have been reported for right and left eye separately. Rows according to visual status categories at specified time points are reported in this end point, only when there was a non-zero data for at least 1 reporting arm. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Number of Subjects Analysed' signifies number of subjects evaluable for this end point and ‘n’ signifies number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	17	15
Units: subjects
Anterior (Lids), Right Eye: Month 12 (n =17, 15)	0	1
Anterior (Lids), Left Eye: Month 12 (n =17, 15)	0	1
Anterior (EMM), Right Eye: Month 24 (n =13, 11)	1	0
Anterior (EMM), Left Eye: Month 24 (n =13, 11)	1	0

No statistical analyses for this end point

Secondary: Part B: Audiological Status of Subjects as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test

Top of page

End point title

Part B: Audiological Status of Subjects as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test

End point description

Audiological evaluations of subjects were recorded and reported using behavior hearing assessment through pure tone audiometry test which included subjects with normal, abnormal, incomplete/inconclusive behavior at month 12 and 24. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here ‘Number of Subjects Analysed’ signifies number of subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	16	12
Units: subjects
Normal Behavior: Month12	11	8
Abnormal Behavior: Month 12	1	4
Incomplete/Inconclusive Behavior: Month 12	4	0
Normal Behavior: Month 24	13	8
Abnormal Behavior: Month 24	0	2
Incomplete/Inconclusive Behavior: Month 24	3	2

No statistical analyses for this end point

Secondary: Part B: Audiological Status of Subjects as Assessed by Bone Conduction Through Pure Tone Audiometry Test

Top of page

End point title

Part B: Audiological Status of Subjects as Assessed by Bone Conduction Through Pure Tone Audiometry Test

End point description

Audiological evaluations of subjects were recorded and reported by bone conduction assessment through pure tone audiometry test which included subjects with sensorineural hearing loss, conductive hearing loss, mixed hearing loss, neural, and unspecified. Rows according to bone conduction categories at specified time points are reported in this end point, only when there was a non-zero data for at least 1 reporting arm. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Number of Subjects Analysed' signifies number of subjects evaluable for this end point and ‘n’ signifies number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	1	2
Units: subjects
Conductive Hearing Loss: Month 12 (n =1, 2)	0	1
Unspecified: Month 12 (n =1, 2)	1	1
Conductive Hearing Loss: Month 24 (n =0, 1)	0	1

No statistical analyses for this end point

Secondary: Part B: Audiological Status of Subjects as Assessed by Air Conduction via Phones/Headphones Through Pure Tone Audiometry Test

Top of page

End point title

Part B: Audiological Status of Subjects as Assessed by Air Conduction via Phones/Headphones Through Pure Tone Audiometry Test

End point description

Audiological evaluations of subjects were recorded and reported by air conduction via phones/headphones through pure tone audiometry test which included subjects with hearing loss ranged from less than or equal to (<=) 20 decibel hearing loss (DB HL), 21-40 DB HL, 41-70 DB HL, 71-90 DB HL, greater than (>) 90 DB HL or no response, and missing at frequencies ranged from 500 Hertz (Hz) to 8000 Hz at month 12 and 24. In this end point, data have been reported for right and left ear separately. Rows according to air conduction categories at specified time points are reported in this end point, only when there was a non-zero data for at least 1 reporting arm. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. 'Number of Subjects Analysed = subjects evaluable for this end point and ‘n’ = number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	8	5
Units: subjects
Right Ear,500 Hz,<=20 DB HL: Month 12 (n =5, 5)	3	4
Right Ear,500 Hz, 21-40 DB HL: Month 12 (n =5, 5)	2	1
Right Ear,1000 Hz,<=20 DB HL: Month 12 (n =5, 5)	4	5
Right Ear,1000 Hz,21-40 DB HL: Month 12 (n =5, 5)	1	0
Right Ear,2000 Hz,<=20 DB HL: Month 12 (n =5, 5)	3	4
Right Ear,2000 Hz,21-40 DB HL: Month 12 (n =5, 5)	2	0
Right Ear,4000 Hz,<=20 DB HL: Month 12 (n =5, 5)	4	5
Right Ear,4000 Hz,21-40 DB HL: Month 12 (n =5, 5)	1	0
Right Ear,8000 Hz,<=20 DB HL: Month 12 (n =5, 5)	3	4
Right Ear,8000 Hz, Missing: Month 12 (n =5, 5)	2	0
Left Ear,500 Hz, <=20 DB HL: Month 12 (n =5, 5)	3	3
Left Ear,500 Hz, 21-40 DB HL: Month 12 (n =5, 5)	2	1
Left Ear,1000 Hz, <=20 DB HL: Month 12 (n =5, 5)	3	5
Left Ear,1000 Hz, 21-40 DB HL: Month 12 (n =5, 5)	2	0
Left Ear,2000 Hz, <=20 DB HL: Month 12 (n =5, 5)	3	4
Left Ear,2000 Hz, 21-40 DB HL: Month 12 (n =5, 5)	2	0
Left Ear,4000 Hz, <=20 DB HL: Month 12 (n =5, 5)	4	5
Left Ear,4000 Hz, 21-40 DB HL: Month 12 (n =5, 5)	1	0
Left Ear,8000 Hz, <=20 DB HL: Month 12 (n =5, 5)	3	4
Left Ear,8000 Hz, Missing: Month 24 (n =5, 5)	2	1
Right Ear,500 Hz, <=20 DB HL: Month 24 (n =8, 4)	5	3
Right Ear,500 Hz, 21-40 DB HL: Month 24 (n =8, 4)	2	0
Right Ear,1000 Hz, <=20 DB HL: Month 24 (n =8, 4)	5	2
Right Ear,1000 Hz, 21-40 DB HL: Month 24 (n =8, 4)	1	0
Right Ear,2000 Hz, <=20 DB HL: Month 24 (n =8, 4)	6	3
Right Ear,2000 Hz, 21-40 DB HL: Month 24 (n =8, 4)	1	0
Right Ear,4000 Hz, <=20 DB HL: Month 24 (n =8, 4)	7	3
Right Ear,8000 Hz, <=20 DB HL: Month 24 (n =8, 4)	4	3
Right Ear,8000 Hz, 21-40 DB HL: Month 24 (n =8, 4)	1	0
Right Ear,8000 Hz, Missing: Month 24 (n =8, 4)	1	0
Left Ear,500 Hz, <=20 DB HL: Month 24 (n =8, 4)	6	3
Left Ear,500 Hz, 21-40 DB HL: Month 24 (n =8, 4)	1	0
Left Ear,1000 Hz, <=20 DB HL: Month 24 (n =8, 4)	4	3
Left Ear,1000 Hz, 21-40 DB HL: Month 24 (n =8, 4)	1	0
Left Ear,2000 Hz, <=20 DB HL: Month 24 (n =8, 4)	6	2
Left Ear,2000 Hz, 21-40 DB HL: Month 24 (n =8, 4)	1	0
Left Ear,4000 Hz, <=20 DB HL: Month 24 (n =8, 4)	7	4
Left Ear,8000 Hz, <=20 DB HL: Month 24 (n =8, 4)	3	3
Left Ear,8000 Hz, 21-40 DB HL: Month 24 (n =8, 4)	1	0
Left Ear,8000 Hz, Missing: Month 24 (n =8, 4)	1	0

No statistical analyses for this end point

Secondary: Part B: Audiological Status of Subjects as Assessed by Air Conduction via Soundfield Through Pure Tone Audiometry Test

Top of page

End point title

Part B: Audiological Status of Subjects as Assessed by Air Conduction via Soundfield Through Pure Tone Audiometry Test

End point description

Audiological evaluations of subjects were recorded and reported by air conduction via soundfield through pure tone audiometry test which included subjects with hearing loss ranged from <=20 DB HL, 21-40 DB HL, 41-70 DB HL, 71-90 DB HL, >90 DB HL or no response, and missing at frequencies ranged from 500 Hz to 4000 Hz at month 12 and 24. Rows according to air conduction categories at specified time points are reported in this end point, only when there was a non-zero data for at least 1 reporting arm. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Number of Subjects Analysed' = number of subjects evaluable for this end point and ‘n’ = number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	13	9
Units: subjects
500 Hz, <=20 DB HL: Month 12 (n =13, 9)	6	2
500 Hz, 21-40 DB HL: Month 12 (n =13, 9)	5	6
500 Hz, 71-90 DB HL: Month 12 (n =13, 9)	1	0
1000 Hz, <=20 DB HL: Month 12 (n =13, 9)	9	3
1000 Hz, 21-40 DB HL: Month 12 (n =13, 9)	1	5
1000 Hz, 71-90 DB HL: Month 12 (n =13, 9)	1	0
2000 Hz, <=20 DB HL: Month 12 (n =13, 9)	7	2
2000 Hz, 21-40 DB HL: Month 12 (n =13, 9)	3	4
2000 Hz, Missing: Month 12 (n =13, 9)	1	0
4000 Hz, <=20 DB HL: Month 12 (n =13, 9)	6	4
4000 Hz, 21-40 DB HL: Month 12 (n =13, 9)	4	4
4000 Hz, 71-90 DB HL: Month 12 (n =13, 9)	1	0
500 Hz, <=20 DB HL: Month 24 (n =11, 9)	6	2
500 Hz, 21-40 DB HL: Month 24 (n =11, 9)	2	5
1000 Hz, <=20 DB HL: Month 24 (n =11, 9)	6	6
1000 Hz, 21-40 DB HL: Month 24 (n =11, 9)	4	3
2000 Hz, <=20 DB HL: Month 24 (n =11, 9)	6	3
2000 Hz, 21-40 DB HL: Month 24 (n =11, 9)	2	4
4000 Hz, <=20 DB HL: Month 24 (n =11, 9)	5	4
4000 Hz, 21-40 DB HL: Month 24 (n =11, 9)	4	3

No statistical analyses for this end point

Secondary: Part B: Audiological Status of Subjects as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test

Top of page

End point title

Part B: Audiological Status of Subjects as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test

End point description

Audiological evaluations of subjects were recorded and reported by tympanometry assessment through immittance audiometry test which included subjects with peak pressure (PP) signs (+) and (-) at month 12 and 24. In this end point, data have been reported for right and left ear separately. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Number of Subjects Analysed' signifies number of subjects evaluable for this end point and ‘n’ signifies number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	9	8
Units: decapascals
arithmetic mean (standard deviation)
PP for Sign (+), Right Ear: Month 12 (n =7, 3)	51.89 ± 63.024	27.33 ± 26.539
PP for Sign (+), Left Ear: Month 12 (n =3, 4)	5.07 ± 4.900	73.75 ± 28.987
PP for Sign (+), Right Ear: Month 24 (n =3, 4)	44.00 ± 46.130	33.50 ± 44.125
PP for Sign (+), Left Ear: Month 24 (n =7, 5)	42.71 ± 50.112	35.00 ± 46.578
PP for Sign (-), Right Ear: Month 12 (n =6, 8)	149.3 ± 144.34	67.75 ± 57.350
PP for Sign (-), Left Ear: Month 12 (n =9, 5)	79.89 ± 64.367	46.80 ± 46.912
PP for Sign (-), Right Ear: Month 24 (n =8, 3)	98.00 ± 55.685	83.67 ± 107.38
PP for Sign (-), Left Ear: Month 24 (n =6, 2)	102.2 ± 84.781	135.0 ± 70.711

No statistical analyses for this end point

Secondary: Part B: Audiological Status of Subjects as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test

Top of page

End point title

Part B: Audiological Status of Subjects as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test

End point description

Audiological evaluations of subjects were recorded and reported by tympanometry assessment through immittance audiometry test which included subjects with static acoustic admittance at month 12 and 24. In this end point, data have been reported for right and left ear separately. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Number of Subjects Analysed' signifies number of subjects evaluable for this end point and ‘n’ signifies number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	9	11
Units: millimho
arithmetic mean (standard deviation)
Right Ear: Month 12 (n =9, 11)	0.241 ± 0.1403	0.403 ± 0.1691
Left Ear: Month 12 (n =8, 9)	0.364 ± 0.1513	0.330 ± 0.1595
Right Ear: Month 24 (n =6, 6)	0.273 ± 0.0784	0.400 ± 0.1321
Left Ear: Month 24 (n =8, 6)	0.295 ± 0.0691	0.585 ± 0.5558

No statistical analyses for this end point

Secondary: Part B: Audiological Status of Subjects as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test

Top of page

End point title

Part B: Audiological Status of Subjects as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test

End point description

Audiological evaluations of subjects were recorded and reported by ipsilateral stapedial reflex through immittance audiometry test which included subjects with presence of ipsilateral stapedial reflex at frequencies ranged from 500 Hz to 2000 Hz at month 12 and 24. Ipsilateral stapedial reflex measures are used to assess the neural pathway surrounding the stapedial reflex, which occurs in response to a loud sound (70 to 90 decibel above threshold). In this end point, data have been reported for right and left ear separately. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Number of Subjects Analysed' signifies number of subjects evaluable for this end point and ‘n’ signifies number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	14	12
Units: subjects
500 Hz, Right Ear: Month 12 (n =14, 12)	5	1
500 Hz, Left Ear: Month 12 (n =14, 12)	6	1
1000 Hz, Right Ear: Month 12 (n =14, 12)	5	1
1000 Hz, Left Ear: Month 12 (n =14, 12)	6	1
2000 Hz, Right Ear: Month 12 (n =14, 12)	5	1
2000 Hz, Left Ear: Month 12 (n =14, 12)	6	1
500 Hz, Right Ear: Month 24 (n =13, 9)	4	2
500 Hz, Left Ear: Month 24 (n =13, 9)	4	2
1000 Hz, Right Ear: Month 24 (n =13, 9)	4	2
1000 Hz, Left Ear: Month 24 (n =13, 9)	5	2
2000 Hz, Right Ear: Month 24 (n =13, 9)	4	2
2000 Hz, Left Ear: Month 24 (n =13, 9)	4	2

No statistical analyses for this end point

Secondary: Part B: Audiological Status of Subjects as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment

Top of page

End point title

Part B: Audiological Status of Subjects as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment

End point description

Audiological evaluations of subjects were recorded and reported by transient evoked emission through otoacoustic emissions assessment which included subjects with presence of transient evoked emissions at frequencies ranged from 1000 Hz to 4000 Hz at month 12 and 24. In this end point, data have been reported for right and left ear separately. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Number of Subjects Analysed' signifies number of subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	7	3
Units: subjects
1000 Hz, Right Ear: Month 12	3	2
1000 Hz, Left Ear: Month 12	2	1
1500 Hz, Right Ear: Month 12	3	2
1500 Hz, Left Ear: Month 12	2	2
2000 Hz, Right Ear: Month 12	5	2
2000 Hz, Left Ear: Month 12	5	2
3000 Hz, Right Ear: Month 12	4	2
3000 Hz, Left Ear: Month 12	4	2
4000 Hz, Right Ear: Month 12	6	2
4000 Hz, Left Ear: Month 12	5	3
1000 Hz, Right Ear: Month 24	3	2
1000 Hz, Left Ear: Month 24	2	2
1500 Hz, Right Ear: Month 24	2	3
1500 Hz, Left Ear: Month 24	2	3
2000 Hz, Right Ear: Month 24	7	3
2000 Hz, Left Ear: Month 24	6	3
3000 Hz, Right Ear: Month 24	6	3
3000 Hz, Left Ear: Month 24	4	3
4000 Hz, Right Ear: Month 24	7	3
4000 Hz, Left Ear: Month 24	5	3

No statistical analyses for this end point

Secondary: Part B: Audiological Status of Subjects as Assessed by Distort Product Through Otoacoustic Emissions Assessment

Top of page

End point title

Part B: Audiological Status of Subjects as Assessed by Distort Product Through Otoacoustic Emissions Assessment

End point description

Audiological evaluations of subjects were recorded and reported by distort product through otoacoustic emissions assessment which included subjects with presence of distort product at frequencies ranged from 2000 Hz to 8000 Hz at month 12 and 24. Distortion-product otoacoustic emissions (DPOAEs) are generated in the cochlea in response to two tones of a given frequency and sound pressure level presented in the ear canal. Distort product otoacoustic emissions are an objective indicator of normally functioning cochlea outer hair cells. In this end point, data have been reported for right and left ear separately. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Number of Subjects Analysed' signifies number of subjects evaluable for this end point and ‘n’ signifies number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	7	7
Units: subjects
2000 Hz, Right Ear: Month 12 (n =6, 6)	4	4
2000 Hz, Left Ear: Month 12 (n =6, 6)	5	3
3000 Hz, Right Ear: Month 12 (n =6, 6)	5	4
3000 Hz, Left Ear: Month 12 (n =6, 6)	5	3
4000 Hz, Right Ear: Month 12 (n =6, 6)	5	4
4000 Hz, Left Ear: Month 12 (n =6, 6)	5	3
6000 Hz, Right Ear: Month 12 (n =6, 6)	4	4
6000 Hz, Left Ear: Month 12 (n =6, 6)	5	4
8000 Hz, Right Ear: Month 12 (n =6, 6)	4	2
8000 Hz, Left Ear: Month 12 (n =6, 6)	5	2
2000 Hz, Right Ear: Month 24 (n =7, 7)	4	7
2000 Hz, Left Ear: Month 24 (n =7, 7)	4	6
3000 Hz, Right Ear: Month 24 (n =7, 7)	7	5
3000 Hz, Left Ear: Month 24 (n =7, 7)	6	5
4000 Hz, Right Ear: Month 24 (n =7, 7)	6	5
4000 Hz, Left Ear: Month 24 (n =7, 7)	6	5
6000 Hz, Right Ear: Month 24 (n =7, 7)	4	6
6000 Hz, Left Ear: Month 24 (n =7, 7)	5	6
8000 Hz, Right Ear: Month 24 (n =7, 7)	3	2
8000 Hz, Left Ear: Month 24 (n =7, 7)	4	2

No statistical analyses for this end point

Secondary: Part B: Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths

Top of page

End point title

Part B: Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths

End point description

An AE was any untoward medical occurrence in a subject who received study medication without regard to possibility of causal relationship to it. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. AEs included both serious and all non-serious AEs. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	27	26
Units: subjects
AEs	17	17
SAEs	9	6
Deaths	0	2

No statistical analyses for this end point

Secondary: Part B: Neurological Progress of Subjects as Assessed by the Neurology Optimality Score

Top of page

End point title

Part B: Neurological Progress of Subjects as Assessed by the Neurology Optimality Score

End point description

The Hammersmith Infant Neurological Examination (HINE) was a standard scoring examination to assess development of cranial nerve; posture; movement; tone; and reflexes and reaction. HINE exam global score is a sum of subset (cranial nerve, posture, movement, tone, reflexes and reactions) scores, ranged from 0 to 78, where higher score represents better outcome. Here, the HINE global scores were reported at month 12 and 24. Part B safety analysis set included all subjects enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Number of Subjects Analysed' signifies number of subjects evaluable for this end point and ‘n’ signifies number of subjects evaluable for each specified rows.

End point type

Secondary

End point timeframe

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

End point values	Part B (Non-Interventional Phase): IV Sildenafil	Part B (Non-Interventional Phase): Placebo
Number of subjects analysed	21	12
Units: units on a scale
arithmetic mean (standard deviation)
Month 12 (n =21, 12)	69.9 ± 14.97	75.6 ± 3.45
Month 24 (n =17, 10)	65.6 ± 19.71	76.5 ± 2.42

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Part A: Baseline up to 31 days after end of study drug infusion (up to 45 days); Part B: up to 24 months after end of study treatment in Part A (maximum up to 26 months)

Adverse event reporting additional description

Same event may appear as both an AE and SAE. An event may be categorized as serious in one subject and as non-serious in another, or a subject may have experienced both a serious and non-serious event. Deaths (all causes) included only treatment emergent serious events. For Part-B (non-interventional) only SAEs and death data was collected.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

Part A: IV Sildenafil

Reporting group description

Reporting group title

Part A: Placebo

Reporting group description

Reporting group title

Part B: IV Sildenafil

Reporting group description

Subjects who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.

Reporting group title

Part B: Placebo

Reporting group description

Subjects who started Part A (not necessarily completed Part A) and who were eligible and consented, continued to be followed up in part B of the study.

Serious adverse events	Part A: IV Sildenafil	Part A: Placebo	Part B: IV Sildenafil	Part B: Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 29 (24.14%)	2 / 30 (6.67%)	9 / 27 (33.33%)	6 / 26 (23.08%)
number of deaths (all causes)	1	1	0	2
number of deaths resulting from adverse events
Investigations
Oxygen saturation decreased
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Skull fracture
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	1 / 27 (3.70%)	0 / 26 (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
Congenital, familial and genetic disorders
Pulmonary malformation
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Congenital heart disease
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertensive crisis
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (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
Hypotension
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiomyopathy
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (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
Congestive cardiomyopathy
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	1 / 27 (3.70%)	0 / 26 (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
Nervous system disorders
Myoclonus
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (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
Seizure
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Drug withdrawal syndrome
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	1 / 27 (3.70%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Food allergy
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	1 / 27 (3.70%)	0 / 26 (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
Gastrointestinal disorders
Gastroenteritis
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	1 / 27 (3.70%)	0 / 26 (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
Gastroesophageal Reflux
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	1 / 27 (3.70%)	0 / 26 (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
Respiratory, thoracic and mediastinal disorders
Respiratory failure
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Apnoea
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	1 / 27 (3.70%)	0 / 26 (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
Pulmonary hypertension crisis
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung disorder
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Urosepsis
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	2 / 27 (7.41%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	1 / 27 (3.70%)	0 / 26 (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
Respiratory syncytial virus infection
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	2 / 27 (7.41%)	3 / 26 (11.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	1 / 27 (3.70%)	0 / 26 (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
Viral upper respiratory tract infection
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	1 / 27 (3.70%)	0 / 26 (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
Urinary tract infection
subjects affected / exposed	0 / 29 (0.00%)	0 / 30 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyponatraemia
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (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

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Part A: IV Sildenafil	Part A: Placebo	Part B: IV Sildenafil	Part B: Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	20 / 29 (68.97%)	19 / 30 (63.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
Vascular disorders
Haemodynamic instability
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	2	0	0	0
Hypertension
subjects affected / exposed	2 / 29 (6.90%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	2	0	0	0
Hypotension
subjects affected / exposed	7 / 29 (24.14%)	3 / 30 (10.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	7	3	0	0
General disorders and administration site conditions
Disease progression
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Drug withdrawal syndrome
subjects affected / exposed	4 / 29 (13.79%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	4	0	0	0
Drug withdrawal syndrome neonatal
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Generalised oedema
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Infusion site extravasation
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0
Malaise
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Oedema
subjects affected / exposed	1 / 29 (3.45%)	3 / 30 (10.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	3	0	0
Secretion discharge
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Withdrawal syndrome
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Reproductive system and breast disorders
Oedema genital
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Atelectasis
subjects affected / exposed	2 / 29 (6.90%)	2 / 30 (6.67%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	2	2	0	0
Choking
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Hiccups
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Hypoxia
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Lung disorder
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	2	0	0
Neonatal asphyxia
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Pneumothorax
subjects affected / exposed	2 / 29 (6.90%)	4 / 30 (13.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	2	4	0	0
Productive cough
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Pulmonary air leakage
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Pulmonary interstitial emphysema syndrome
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Pulmonary oedema
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Respiratory distress
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Respiratory failure
subjects affected / exposed	0 / 29 (0.00%)	2 / 30 (6.67%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	2	0	0
Respiratory tract oedema
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Stridor
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Tachypnoea
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Psychiatric disorders
Selective eating disorder
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Blood albumin decreased
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Blood calcium decreased
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Blood magnesium decreased
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Blood methaemoglobin present
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	2	0	0	0
Blood urea increased
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
C-reactive protein increased
subjects affected / exposed	0 / 29 (0.00%)	3 / 30 (10.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	4	0	0
Haematocrit decreased
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Hepatic enzyme increased
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Oxygen saturation decreased
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
PCO2 decreased
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Staphylococcus test positive
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Thyroid function test abnormal
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Injury, poisoning and procedural complications
Procedural hypertension
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Procedural hypotension
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Transfusion reaction
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Underdose
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Congenital, familial and genetic disorders
Persistent foetal circulation
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Cardiac disorders
Bradycardia
subjects affected / exposed	3 / 29 (10.34%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	3	1	0	0
Bradycardia neonatal
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Junctional ectopic tachycardia
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Myocardial ischaemia
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Sinus bradycardia
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Supraventricular tachycardia
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Nervous system disorders
Brain injury
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Cerebral ischaemia
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Hypertonia
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Motor dysfunction
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Seizure
subjects affected / exposed	2 / 29 (6.90%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	2	1	0	0
Vocal cord paralysis
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	4 / 29 (13.79%)	3 / 30 (10.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	5	3	0	0
Leukocytosis
subjects affected / exposed	2 / 29 (6.90%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	2	1	0	0
Thrombocytopenia
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Eye disorders
Eye oedema
subjects affected / exposed	2 / 29 (6.90%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	2	0	0	0
Periorbital oedema
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Pupil fixed
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	1 / 29 (3.45%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	1	0	0
Diarrhoea
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Gastric haemorrhage
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	2	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 29 (6.90%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	2	1	0	0
Intestinal perforation
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Vomiting
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Hepatobiliary disorders
Cholestasis
subjects affected / exposed	2 / 29 (6.90%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	2	1	0	0
Hyperbilirubinaemia
subjects affected / exposed	1 / 29 (3.45%)	3 / 30 (10.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	3	0	0
Jaundice cholestatic
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Skin and subcutaneous tissue disorders
Dermatitis diaper
subjects affected / exposed	0 / 29 (0.00%)	2 / 30 (6.67%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	2	0	0
Rash
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Rash erythematous
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Skin irritation
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Renal and urinary disorders
Oliguria
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Renal failure
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Infections and infestations
Conjunctivitis
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Lung infection
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Nosocomial infection
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Pneumonia
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Sepsis
subjects affected / exposed	0 / 29 (0.00%)	2 / 30 (6.67%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	3	0	0
Tracheitis
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Metabolism and nutrition disorders
Acidosis
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Alkalosis hypochloraemic
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Feeding intolerance
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Fluid overload
subjects affected / exposed	2 / 29 (6.90%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	2	0	0	0
Fluid retention
subjects affected / exposed	1 / 29 (3.45%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	1	0	0
Hyperchloraemia
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Hyperkalaemia
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0
Hypernatraemia
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Hypoalbuminaemia
subjects affected / exposed	1 / 29 (3.45%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	1	0	0
Hypocalcaemia
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Hypochloraemia
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Hypoglycaemia
subjects affected / exposed	0 / 29 (0.00%)	1 / 30 (3.33%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0
Hypokalaemia
subjects affected / exposed	7 / 29 (24.14%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	8	0	0	0
Hypoproteinaemia
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0
Metabolic acidosis
subjects affected / exposed	1 / 29 (3.45%)	0 / 30 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0

More information

Top of page

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.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Subjects Without Treatment Failure

Primary: Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Subjects Without Treatment Failure

Primary: Treatment Failure Rate

Primary: Treatment Failure Rate

Secondary: Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation

Secondary: Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation

Secondary: Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure

Secondary: Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure

Secondary: Percentage of Subjects With Individual Components of Treatment Failure

Secondary: Percentage of Subjects With Individual Components of Treatment Failure

Secondary: Change From Baseline in Oxygenation Index (OI) at Hour 6, 12 and 24

Secondary: Change From Baseline in Oxygenation Index (OI) at Hour 6, 12 and 24

Secondary: Change From Baseline in Differential Saturation at Hour 6, 12 and 24

Secondary: Change From Baseline in Differential Saturation at Hour 6, 12 and 24

Secondary: Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hour 6, 12 and 24

Secondary: Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hour 6, 12 and 24

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Number of Treatment-Emergent Adverse Events (AEs) According to Severity

Secondary: Number of Treatment-Emergent Adverse Events (AEs) According to Severity

Secondary: Number of Subjects With Laboratory Abnormalities

Secondary: Number of Subjects With Laboratory Abnormalities

Secondary: Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Subjects as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)

Secondary: Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Subjects as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)

Secondary: Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire of Subjects as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)

Secondary: Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire of Subjects as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)

Secondary: Part B: Number of Subjects With Eye Movement Disorders as Assessed by Eye Examination

Secondary: Part B: Number of Subjects With Eye Movement Disorders as Assessed by Eye Examination

Secondary: Part B: Visual Acuity of Verbal Subjects as Assessed by Ophthalmological Assessment

Secondary: Part B: Visual Acuity of Verbal Subjects as Assessed by Ophthalmological Assessment

Secondary: Part B: Visual Acuity of Non-Verbal Subjects as Assessed by Ophthalmological Assessment

Secondary: Part B: Visual Acuity of Non-Verbal Subjects as Assessed by Ophthalmological Assessment

Secondary: Part B: Visual Acuity of Verbal Subjects as Assessed by LogMAR Through Visual Acuity Chart

Secondary: Part B: Visual Acuity of Verbal Subjects as Assessed by LogMAR Through Visual Acuity Chart

Secondary: Part B: Visual Status of Subjects With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments

Secondary: Part B: Visual Status of Subjects With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments

Secondary: Part B: Audiological Status of Subjects as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Bone Conduction Through Pure Tone Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Bone Conduction Through Pure Tone Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Air Conduction via Phones/Headphones Through Pure Tone Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Air Conduction via Phones/Headphones Through Pure Tone Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Air Conduction via Soundfield Through Pure Tone Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Air Conduction via Soundfield Through Pure Tone Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test

Secondary: Part B: Audiological Status of Subjects as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment

Secondary: Part B: Audiological Status of Subjects as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment

Secondary: Part B: Audiological Status of Subjects as Assessed by Distort Product Through Otoacoustic Emissions Assessment

Secondary: Part B: Audiological Status of Subjects as Assessed by Distort Product Through Otoacoustic Emissions Assessment

Secondary: Part B: Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths

Secondary: Part B: Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths

Secondary: Part B: Neurological Progress of Subjects as Assessed by the Neurology Optimality Score

Secondary: Part B: Neurological Progress of Subjects as Assessed by the Neurology Optimality Score

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information