Pulmonary Hypertension, Familial Persistent, of the Newborn
Conditions
Keywords
persistent pulmonary hypertension, newborn, neonates, iv sildenafil, hypoxic respiratory failure and at risk of persistent pulmonary hypertension of the newborn
Brief summary
This study will evaluate whether IV sildenafil can reduce the time on inhaled nitric oxide treatment and reduce the failure rate of available treatments for persistent pulmonary hypertension of the newborn.
Interventions
DRUGplacebo
IV placebo or 0.9% sodium chloride or 10% dextrose. Infusion rate based on weight.
DRUGiv sildenafil
loading dose of 0.1 mg/kg over 30 minutes followed by maintenance dose of 0.03 mg/kg/h. To infuse minimum 48 hours and maximum of 14 days.
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
0 Days to 4 Days
Healthy volunteers
No
Inclusion criteria
* Neonates with persistent pulmonary hypertension of the newborn * Age \<=96 hours and \>=34 weeks gestational age * Oxygenation Index \>15 and \<60 * Concurrent treatment with inhaled nitric oxide and \>=50% oxygen
Exclusion criteria
* Prior or immediate need for extracorporeal membrane oxygenation or cardiopulmonary resuscitation * Expected duration of mechanical ventilation \<48 hours * Profound hypoxemia * Life-threatening or lethal congenital anomaly
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Participants Without Treatment Failure | 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days) | Time in days, on iNO treatment, for participants 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. |
| Treatment Failure Rate | 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days) | Treatment failure rate was defined as percentage of participants who needed additional treatment targeting PPHN, needed ECMO, or died during the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Individual Components of Treatment Failure | 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days) | Percentage of participants with individual components of treatment failure (need to start additional treatment targeting PPHN, need to start ECMO, or death) were evaluated. Some participants could have had multiple qualifying events for treatment failure. |
| Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion | Baseline, Hours 6, 12 and 24 after start of infusion | 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. |
| Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion | Baseline, Hours 6, 12 and 24 after start of infusion | 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. |
| Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hours 6, 12 and 24 | Baseline, Hours 6, 12 and 24 after start of infusion | 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. |
| Maximum Plasma Concentration (Cmax) of Sildenafil and Its Metabolite | Loading dose, Day 1: prior to the start of infusion, 5, 30 minutes after end of loading infusion; Maintenance dose: 48 to 72, 96 to 120 hours during infusion and immediately prior to end of maintenance infusion (up to maximum on Day 14) | Cmax was obtained for Sildenafil and its major metabolite UK-103,320. |
| Total Plasma Clearance (CL) of Sildenafil and Its Metabolite | Loading dose: prior to the start of infusion, 5, 30 minutes after end of loading infusion on Day 1; Maintenance dose: between 48 to 72, 96 to 120 hours during infusion and immediately prior to end of infusion on Day 1 | CL is volume of the body fluid/ plasma from which the drug or the metabolite is completely removed per unit time. CL was obtained for Sildenafil and its major metabolite UK-103,320. |
| Central Volume of Distribution (Vc) of Sildenafil and Its Metabolite | Loading dose: prior to the start of infusion, 5, 30 minutes after end of loading infusion on Day 1; Maintenance dose: between 48 to 72, 96 to 120 hours during infusion and immediately prior to end of infusion on Day 1 | Vc is the hypothetical volume into which a drug or a metabolite initially distributes upon administration. It was determined by using a population-based analysis, non-linear mixed-effects modeling (NONMEM), version 7.4.0. Vc was calculated for Sildenafil and its major metabolite, UK-103,320. |
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 31 days after end of study drug infusion (up to 45 days) | 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. |
| Number of Treatment-Emergent Adverse Events (AEs) According to Severity | Baseline up to 31 days after end of study drug infusion (up to 45 days) | AE: untoward medical occurrence in a participant 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 participant's usual function and severe=interfered significantly with participant's usual function. Missing baseline severities were imputed as mild. |
| Number of Participants With Laboratory Abnormalities | Up to 14 days from initiation of study drug infusion | 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. |
| Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | 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. In this outcome measure composite scores for infants and toddlers were reported at month 12 and 24. |
| Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Month 24 after end of study treatment in Part A (Day 1 to 14) | 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. In this outcome measure composite scores for parent/caregiver were reported at month 24. |
| Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | Standard age-appropriate ophthalmological examinations were used to assess eye movement disorders (presence of amblyopia, strabismus, and nystagmus) at month 12 and 24. In this outcome measure, 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 outcome measure, only when there was a non-zero data for at least 1 reporting arm. |
| Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | 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 outcome measure, data have been reported for right and left eye separately. Rows according to visual acuity categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm. |
| Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation | 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days) | Time in days, from initiation of IV study drug to final weaning of mechanical ventilation among participants achieving final weaning of mechanical ventilation for PPHN was evaluated. Kaplan-Meier method was used for estimation. For participants with mechanical ventilation beyond 336 hours (14 days) from initiation of IV study drug, data was censored at 14 days. |
| Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | 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. Participants 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 participant, divided by distance at which participant was able to see/read chart without impairment; expressed as decimal, logMAR = log10 (1/decimal VA). In this outcome measure, data have been reported for right and left eye separately. |
| Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | 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 and eye movements at month 12 and 24. In this outcome measure, data have been reported for right and left eye separately. Rows according to visual status categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm. |
| Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | Audiological evaluations of participants were recorded and reported using behavior hearing assessment through pure tone audiometry test which includes participants with normal, abnormal, incomplete/inconclusive behavior at month 12 and 24. |
| Part B: Audiological Status of Participants as Assessed by Bone Conduction Through Pure Tone Audiometry Test | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | Audiological evaluations of participants were recorded and reported by bone conduction assessment through pure tone audiometry test which included participants with sensorineural hearing loss, conductive hearing loss, mixed hearing loss, neural, and unspecified at month 12 and 24. Rows according to bone conduction categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm. |
| Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | Audiological evaluations of participants were recorded and reported by air conduction via phones/headphones through pure tone audiometry test which included participants 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 outcome measure, data have been reported for right and left ear separately. Rows according to air conduction categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm. |
| Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | Audiological evaluations of participants were recorded and reported by air conduction via soundfield through pure tone audiometry test which included participants 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 outcome measure, only when there was a non-zero data for at least 1 reporting arm. |
| Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | Audiological evaluations of participants were recorded and reported by tympanometry assessment through immittance audiometry test which included participants with peak pressure signs (+) and (-) at month 12 and 24. In this outcome measure, data have been reported for right and left ear separately. |
| Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | Audiological evaluations of participants were recorded and reported by tympanometry assessment through immittance audiometry test which included participants with static acoustic admittance at month 12 and 24. In this outcome measure, data have been reported for right and left ear separately. |
| Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | Audiological evaluations of participants were recorded and reported by ipsilateral stapedial reflex through immittance audiometry test which included participants 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 outcome measure, data have been reported for right and left ear separately. |
| Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | Audiological evaluations of participants were recorded and reported by transient evoked emission through otoacoustic emissions assessment which included participants with presence of transient evoked emissions from frequencies 1000 Hz to 4000 Hz at month 12 and 24. In this outcome measure, data have been reported for right and left ear separately. |
| Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | Audiological evaluations of participants were recorded and reported by distort product through otoacoustic emissions assessment which included participants 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 outcome measure, data have been reported for right and left ear separately. |
| Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths | up to 24 months after end of study treatment in Part A (maximum up to 26 months) | An AE was any untoward medical occurrence in a participant 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: Neurological Progress of Participants as Assessed by the Neurology Optimality Score | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | 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: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Month 12 and 24 after end of study treatment in Part A (Day 1 to 14) | Standard age-appropriate ophthalmological examinations were used to assess visual acuity (performed differently for children unable of verbal interaction) through fixates and follows (included central, steady and maintained), light perception (wince to light), no light perception, and missing at month 12 and 24. In this outcome measure, data have been reported for right and left eye separately. Rows according to visual acuity categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm. |
| Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure | 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days) | 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 participants with treatment failure was evaluated. Kaplan-Meier method was used for estimation. For participants without treatment failure by the endpoint assessment date, data was censored at the endpoint assessment date. |
Countries
Belgium, Canada, Denmark, France, Germany, Italy, Netherlands, Norway, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
This study was planned in two parts Part A (double-blind phase) and Part B (long-term, non-intervention phase).
Pre-assignment details
Neonates with persistent pulmonary hypertension of the newborn (PPHN) or hypoxic respiratory failure (HRF) and at risk of PPHN who were receiving inhaled nitric oxide (iNO) treatment were evaluated in this study.
Participants by arm
| Arm | Count |
|---|---|
| IV Sildenafil Part A: Participants 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 participants' safety and well-being. Part B: Participants 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. | 29 |
| Placebo Participants received placebo (0.9 % normal saline or dextrose 10%) at a rate matched to sildenafil infusion, intravenously, based on participant's weight, for a minimum of 2 days and maximum of 14 days. Infusion continuation was upon investigator discretion in view of participants' safety and well-being. Part B: Participants 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. | 30 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part A | Adverse Event | 2 | 2 |
| Part A | Death | 2 | 1 |
| Part A | Insufficient Clinical Response | 2 | 4 |
| Part A | Lost to Follow-up | 0 | 1 |
| Part A | Missed 28 day follow-up visit | 1 | 1 |
| Part A | Other | 0 | 1 |
| Part A | Withdrawal by Subject | 0 | 1 |
| Part B | Death | 0 | 2 |
| Part B | Lost to Follow-up | 2 | 3 |
| Part B | No longer willing to participate in study | 1 | 4 |
| Part B | Other | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | IV Sildenafil |
|---|---|---|---|
| Age, Continuous | 1.9 days STANDARD_DEVIATION 0.75 | 1.8 days STANDARD_DEVIATION 0.83 | 1.7 days STANDARD_DEVIATION 0.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 52 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 8 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) White | 16 Participants | 35 Participants | 19 Participants |
| Sex: Female, Male Female | 13 Participants | 26 Participants | 13 Participants |
| Sex: Female, Male Male | 17 Participants | 33 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 29 | 1 / 30 | 0 / 27 | 2 / 26 |
| other Total, other adverse events | 20 / 29 | 19 / 30 | 14 / 27 | 15 / 26 |
| serious Total, serious adverse events | 7 / 29 | 2 / 30 | 9 / 27 | 6 / 26 |
Outcome results
Primary
Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Participants Without Treatment Failure
Time in days, on iNO treatment, for participants 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.
Time frame: 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
Population: The intent-to-treat population (ITT) included all randomized participants treated with study treatment. Here Overall number of participants analyzed signifies number of participants without iNO treatment failure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| IV Sildenafil | Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Participants Without Treatment Failure | 4.1 days |
| Placebo | Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Participants Without Treatment Failure | 4.1 days |
p-value: 0.98595% CI: [-2.08, 2.04]ANCOVA
Primary
Treatment Failure Rate
Treatment failure rate was defined as percentage of participants who needed additional treatment targeting PPHN, needed ECMO, or died during the study.
Time frame: 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
Population: The ITT population included all randomized participants treated with study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Sildenafil | Treatment Failure Rate | 27.6 percentage of participants |
| Placebo | Treatment Failure Rate | 20.0 percentage of participants |
p-value: 0.493595% CI: [-14.1, 29.3]Chi-squared
Secondary
Central Volume of Distribution (Vc) of Sildenafil and Its Metabolite
Vc is the hypothetical volume into which a drug or a metabolite initially distributes upon administration. It was determined by using a population-based analysis, non-linear mixed-effects modeling (NONMEM), version 7.4.0. Vc was calculated for Sildenafil and its major metabolite, UK-103,320.
Time frame: Loading dose: prior to the start of infusion, 5, 30 minutes after end of loading infusion on Day 1; Maintenance dose: between 48 to 72, 96 to 120 hours during infusion and immediately prior to end of infusion on Day 1
Population: PK analysis set included all participants randomized and treated who had at least 1 concentration during whole treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Sildenafil | Central Volume of Distribution (Vc) of Sildenafil and Its Metabolite | Sildenafil | 8.76 Liters | Standard Deviation 1.8 |
| IV Sildenafil | Central Volume of Distribution (Vc) of Sildenafil and Its Metabolite | UK-103,320 | 15.96 Liters | Standard Deviation 11.2 |
Secondary
Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion
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.
Time frame: Baseline, Hours 6, 12 and 24 after start of infusion
Population: The ITT population included all randomized participants treated with study treatment. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified rows.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| IV Sildenafil | Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion | Change at Hour 6 | 1.5 percentage of hemoglobin |
| IV Sildenafil | Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion | Change at Hour 12 | -1.2 percentage of hemoglobin |
| IV Sildenafil | Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion | Change at Hour 24 | 1.2 percentage of hemoglobin |
| Placebo | Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion | Change at Hour 6 | 0.8 percentage of hemoglobin |
| Placebo | Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion | Change at Hour 12 | 6.7 percentage of hemoglobin |
| Placebo | Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion | Change at Hour 24 | 9.3 percentage of hemoglobin |
Comparison: Hour 6p-value: 0.768695% CI: [-4.3, 5.8]ANCOVA
Comparison: Hour 12p-value: 0.111295% CI: [-17.8, 1.9]ANCOVA
Comparison: Hour 24p-value: 0.208995% CI: [-21.2, 4.8]ANCOVA
Secondary
Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion
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.
Time frame: Baseline, Hours 6, 12 and 24 after start of infusion
Population: The ITT population included all randomized participants treated with study treatment. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified rows.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| IV Sildenafil | Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion | Change at Hour 12 | -4.1 cmH2O/mmHg |
| IV Sildenafil | Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion | Change at Hour 24 | -11.6 cmH2O/mmHg |
| IV Sildenafil | Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion | Change at Hour 6 | -4.2 cmH2O/mmHg |
| Placebo | Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion | Change at Hour 6 | -8.0 cmH2O/mmHg |
| Placebo | Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion | Change at Hour 12 | -8.2 cmH2O/mmHg |
| Placebo | Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion | Change at Hour 24 | -9.5 cmH2O/mmHg |
Comparison: Hour 6p-value: 0.498495% CI: [-7.5, 15.3]ANCOVA
Comparison: Hour 12p-value: 0.395695% CI: [-5.5, 13.7]ANCOVA
Comparison: Hour 24p-value: 0.424995% CI: [-7.6, 3.3]ANCOVA
Secondary
Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hours 6, 12 and 24
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.
Time frame: Baseline, Hours 6, 12 and 24 after start of infusion
Population: The ITT population included all randomized participants treated with study treatment. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified rows.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| IV Sildenafil | Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hours 6, 12 and 24 | Change at Hour 6 | 45.3 ratio |
| IV Sildenafil | Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hours 6, 12 and 24 | Change at Hour 12 | 43.4 ratio |
| IV Sildenafil | Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hours 6, 12 and 24 | Change at Hour 24 | 94.6 ratio |
| Placebo | Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hours 6, 12 and 24 | Change at Hour 6 | 8.1 ratio |
| Placebo | Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hours 6, 12 and 24 | Change at Hour 12 | 16.9 ratio |
| Placebo | Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hours 6, 12 and 24 | Change at Hour 24 | 14.7 ratio |
Comparison: Hour 6p-value: 0.082995% CI: [-5, 79.5]ANCOVA
Comparison: Hour 12p-value: 0.180295% CI: [-12.7, 65.9]ANCOVA
Comparison: Hour 24p-value: 0.157695% CI: [-32.5, 192.2]ANCOVA
Secondary
Maximum Plasma Concentration (Cmax) of Sildenafil and Its Metabolite
Cmax was obtained for Sildenafil and its major metabolite UK-103,320.
Time frame: Loading dose, Day 1: prior to the start of infusion, 5, 30 minutes after end of loading infusion; Maintenance dose: 48 to 72, 96 to 120 hours during infusion and immediately prior to end of maintenance infusion (up to maximum on Day 14)
Population: Pharmacokinetic (PK) analysis set included all participants randomized and treated who had at least 1 concentration during whole treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Sildenafil | Maximum Plasma Concentration (Cmax) of Sildenafil and Its Metabolite | Maintenance dose: Sildenafil | 78.12 nanogram per milliliter | Standard Deviation 48.63 |
| IV Sildenafil | Maximum Plasma Concentration (Cmax) of Sildenafil and Its Metabolite | Maintenance dose: UK-103320 | 21.65 nanogram per milliliter | Standard Deviation 11.57 |
| IV Sildenafil | Maximum Plasma Concentration (Cmax) of Sildenafil and Its Metabolite | Loading dose: Sildenafil | 52.64 nanogram per milliliter | Standard Deviation 27.91 |
| IV Sildenafil | Maximum Plasma Concentration (Cmax) of Sildenafil and Its Metabolite | Loading dose: UK-103320 | 1.04 nanogram per milliliter | Standard Deviation 1.68 |
Secondary
Number of Participants With Laboratory Abnormalities
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.
Time frame: Up to 14 days from initiation of study drug infusion
Population: The safety population included all participants treated with study treatment. Here Overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Sildenafil | Number of Participants With Laboratory Abnormalities | 27 Participants |
| Placebo | Number of Participants With Laboratory Abnormalities | 22 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: Baseline up to 31 days after end of study drug infusion (up to 45 days)
Population: The safety population included all participants treated with study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 22 Participants |
| IV Sildenafil | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 7 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 19 Participants |
Secondary
Number of Treatment-Emergent Adverse Events (AEs) According to Severity
AE: untoward medical occurrence in a participant 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 participant's usual function and severe=interfered significantly with participant's usual function. Missing baseline severities were imputed as mild.
Time frame: Baseline up to 31 days after end of study drug infusion (up to 45 days)
Population: The safety population included all participants treated with study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IV Sildenafil | Number of Treatment-Emergent Adverse Events (AEs) According to Severity | Moderate | 29 events |
| IV Sildenafil | Number of Treatment-Emergent Adverse Events (AEs) According to Severity | Mild | 49 events |
| IV Sildenafil | Number of Treatment-Emergent Adverse Events (AEs) According to Severity | Severe | 12 events |
| Placebo | Number of Treatment-Emergent Adverse Events (AEs) According to Severity | Mild | 42 events |
| Placebo | Number of Treatment-Emergent Adverse Events (AEs) According to Severity | Moderate | 24 events |
| Placebo | Number of Treatment-Emergent Adverse Events (AEs) According to Severity | Severe | 17 events |
Secondary
Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test
Audiological evaluations of participants were recorded and reported by air conduction via phones/headphones through pure tone audiometry test which included participants 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 outcome measure, data have been reported for right and left ear separately. Rows according to air conduction categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 500 Hz, <=20 DB HL: Month 12 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 500 Hz, 21 - 40 DB HL: Month 12 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 1000 Hz, <=20 DB HL: Month 12 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 1000 Hz, 21 - 40 DB HL: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 2000 Hz, <=20 DB HL: Month 12 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 2000 Hz, 21 - 40 DB HL: Month 12 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 4000 Hz, <=20 DB HL: Month 12 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 4000 Hz, 21 - 40 DB HL: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 8000 Hz, <=20 DB HL: Month 12 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 8000 Hz, Missing: Month 12 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 500 Hz, <=20 DB HL: Month 12 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 500 Hz, 21 - 40 DB HL: Month 12 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 1000 Hz, <=20 DB HL: Month 12 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 1000 Hz, 21 - 40 DB HL: Month 12 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 2000 Hz, <=20 DB HL: Month 12 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 2000 Hz, 21 - 40 DB HL: Month 12 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 4000 Hz, <=20 DB HL: Month 12 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 4000 Hz, 21 - 40 DB HL: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 8000 Hz, <=20 DB HL: Month 12 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 8000 Hz, Missing: Month 12 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 500 Hz, <=20 DB HL: Month 24 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 500 Hz, 21-40 DB HL: Month 24 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 1000 Hz, <=20 DB HL: Month 24 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 1000 Hz, 21-40 DB HL: Month 24 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 2000 Hz, <=20 DB HL: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 2000 Hz, 21-40 DB HL: Month 24 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 4000 Hz, <=20 DB HL: Month 24 | 7 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 8000 Hz, <=20 DB HL: Month 24 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 8000 Hz, 21-40 DB HL: Month 24 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 8000 Hz, Missing: Month 24 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 500 Hz, <=20 DB HL: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 500 Hz, 21-40 DB HL: Month 24 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 1000 Hz, <=20 DB HL: Month 24 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 1000 Hz, 21-40 DB HL: Month 24 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 2000 Hz, <=20 DB HL: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 2000 Hz, 21-40 DB HL: Month 24 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 4000 Hz, <=20 DB HL: Month 24 | 7 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 8000 Hz, <=20 DB HL: Month 24 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 8000 Hz, 21-40 DB HL: Month 24 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 8000 Hz, Missing: Month 24 | 1 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 8000 Hz, <=20 DB HL: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 500 Hz, <=20 DB HL: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 500 Hz, <=20 DB HL: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 500 Hz, 21 - 40 DB HL: Month 12 | 1 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 500 Hz, <=20 DB HL: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 1000 Hz, <=20 DB HL: Month 12 | 5 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 500 Hz, 21-40 DB HL: Month 24 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 1000 Hz, 21 - 40 DB HL: Month 12 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 2000 Hz, 21-40 DB HL: Month 24 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 2000 Hz, <=20 DB HL: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 1000 Hz, <=20 DB HL: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 2000 Hz, 21 - 40 DB HL: Month 12 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 500 Hz, 21-40 DB HL: Month 24 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 4000 Hz, <=20 DB HL: Month 12 | 5 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 1000 Hz, 21-40 DB HL: Month 24 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 4000 Hz, 21 - 40 DB HL: Month 12 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 8000 Hz, Missing: Month 24 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 8000 Hz, <=20 DB HL: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 2000 Hz, <=20 DB HL: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 8000 Hz, Missing: Month 12 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 1000 Hz, <=20 DB HL: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 500 Hz, <=20 DB HL: Month 12 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 2000 Hz, 21-40 DB HL: Month 24 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 500 Hz, 21 - 40 DB HL: Month 12 | 1 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 4000 Hz, <=20 DB HL: Month 24 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 1000 Hz, <=20 DB HL: Month 12 | 5 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 4000 Hz, <=20 DB HL: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 1000 Hz, 21 - 40 DB HL: Month 12 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 1000 Hz, 21-40 DB HL: Month 24 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 2000 Hz, <=20 DB HL: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 8000 Hz, <=20 DB HL: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 2000 Hz, 21 - 40 DB HL: Month 12 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 8000 Hz, 21-40 DB HL: Month 24 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 4000 Hz, <=20 DB HL: Month 12 | 5 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 8000 Hz, 21-40 DB HL: Month 24 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 4000 Hz, 21 - 40 DB HL: Month 12 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 2000 Hz, <=20 DB HL: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 8000 Hz, <=20 DB HL: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Right Ear, 8000 Hz, Missing: Month 24 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test | Left Ear, 8000 Hz, Missing: Month 12 | 1 Participants |
Secondary
Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test
Audiological evaluations of participants were recorded and reported by air conduction via soundfield through pure tone audiometry test which included participants 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 outcome measure, only when there was a non-zero data for at least 1 reporting arm.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 500 Hz, <=20 DB HL: Month 12 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 500 Hz, 21-40 DB HL: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 500 Hz, 71-90 DB HL: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 1000 Hz, <=20 DB HL: Month 12 | 9 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 1000 Hz, 21-40 DB HL: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 1000 Hz, 71-90 DB HL: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 2000 Hz, <=20 DB HL: Month 12 | 7 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 2000 Hz, 21-40 DB HL: Month 12 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 2000 Hz, Missing: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 4000 Hz, <=20 DB HL: Month 12 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 4000 Hz, 21-40 DB HL: Month 12 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 4000 Hz, 71-90 DB HL: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 500 Hz, <=20 DB HL: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 500 Hz, 21-40 DB HL: Month 24 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 1000 Hz, <=20 DB HL: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 1000 Hz, 21-40 DB HL: Month 24 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 2000 Hz, <=20 DB HL: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 2000 Hz, 21-40 DB HL: Month 24 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 4000 Hz, <=20 DB HL: Month 24 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 4000 Hz, 21-40 DB HL: Month 24 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 2000 Hz, 21-40 DB HL: Month 24 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 500 Hz, <=20 DB HL: Month 12 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 4000 Hz, 21-40 DB HL: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 500 Hz, 21-40 DB HL: Month 12 | 6 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 1000 Hz, 21-40 DB HL: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 500 Hz, 71-90 DB HL: Month 12 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 4000 Hz, 71-90 DB HL: Month 12 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 1000 Hz, <=20 DB HL: Month 12 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 4000 Hz, 21-40 DB HL: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 1000 Hz, 21-40 DB HL: Month 12 | 5 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 500 Hz, <=20 DB HL: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 1000 Hz, 71-90 DB HL: Month 12 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 2000 Hz, <=20 DB HL: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 2000 Hz, <=20 DB HL: Month 12 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 500 Hz, 21-40 DB HL: Month 24 | 5 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 2000 Hz, 21-40 DB HL: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 4000 Hz, <=20 DB HL: Month 24 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 2000 Hz, Missing: Month 12 | 0 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 1000 Hz, <=20 DB HL: Month 24 | 6 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test | 4000 Hz, <=20 DB HL: Month 12 | 4 Participants |
Secondary
Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test
Audiological evaluations of participants were recorded and reported using behavior hearing assessment through pure tone audiometry test which includes participants with normal, abnormal, incomplete/inconclusive behavior at month 12 and 24.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Normal Behavioral Assessment: Month 12 | 11 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Abnormal Behavioral Assessment: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Incomplete/Inconclusive Behavioral Assessment: Month 12 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Normal Behavioral Assessment: Month 24 | 13 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Abnormal Behavioral Assessment: Month 24 | 0 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Incomplete/Inconclusive Behavioral Assessment: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Abnormal Behavioral Assessment: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Normal Behavioral Assessment: Month 12 | 8 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Normal Behavioral Assessment: Month 24 | 8 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Abnormal Behavioral Assessment: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Incomplete/Inconclusive Behavioral Assessment: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test | Incomplete/Inconclusive Behavioral Assessment: Month 12 | 0 Participants |
Secondary
Part B: Audiological Status of Participants as Assessed by Bone Conduction Through Pure Tone Audiometry Test
Audiological evaluations of participants were recorded and reported by bone conduction assessment through pure tone audiometry test which included participants with sensorineural hearing loss, conductive hearing loss, mixed hearing loss, neural, and unspecified at month 12 and 24. Rows according to bone conduction categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Bone Conduction Through Pure Tone Audiometry Test | Conductive Hearing Loss: Month 12 | 0 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Bone Conduction Through Pure Tone Audiometry Test | Unspecified: Month 12 | 1 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Bone Conduction Through Pure Tone Audiometry Test | Unspecified: Month 12 | 1 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Bone Conduction Through Pure Tone Audiometry Test | Conductive Hearing Loss: Month 12 | 1 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Bone Conduction Through Pure Tone Audiometry Test | Conductive Hearing Loss: Month 24 | 1 Participants |
Secondary
Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment
Audiological evaluations of participants were recorded and reported by distort product through otoacoustic emissions assessment which included participants 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 outcome measure, data have been reported for right and left ear separately.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 2000 Hz, Right Ear: Month 12 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 2000 Hz, Left Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 3000 Hz, Right Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 3000 Hz, Left Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 4000 Hz, Right Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 4000 Hz, Left Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 6000 Hz, Right Ear: Month 12 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 6000 Hz, Left Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 8000 Hz, Right Ear: Month 12 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 8000 Hz, Left Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 2000 Hz, Right Ear: Month 24 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 2000 Hz, Left Ear: Month 24 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 3000 Hz, Right Ear: Month 24 | 7 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 3000 Hz, Left Ear: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 4000 Hz, Right Ear: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 4000 Hz, Left Ear: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 6000 Hz, Right Ear: Month 24 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 6000 Hz, Left Ear: Month 24 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 8000 Hz, Right Ear: Month 24 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 8000 Hz, Left Ear: Month 24 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 6000 Hz, Left Ear: Month 24 | 6 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 2000 Hz, Right Ear: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 2000 Hz, Right Ear: Month 24 | 7 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 2000 Hz, Left Ear: Month 12 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 4000 Hz, Left Ear: Month 24 | 5 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 3000 Hz, Right Ear: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 2000 Hz, Left Ear: Month 24 | 6 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 3000 Hz, Left Ear: Month 12 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 8000 Hz, Left Ear: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 4000 Hz, Right Ear: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 3000 Hz, Right Ear: Month 24 | 5 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 4000 Hz, Left Ear: Month 12 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 6000 Hz, Right Ear: Month 24 | 6 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 6000 Hz, Right Ear: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 3000 Hz, Left Ear: Month 24 | 5 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 6000 Hz, Left Ear: Month 12 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 8000 Hz, Right Ear: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 8000 Hz, Right Ear: Month 12 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 4000 Hz, Right Ear: Month 24 | 5 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment | 8000 Hz, Left Ear: Month 12 | 2 Participants |
Secondary
Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test
Audiological evaluations of participants were recorded and reported by ipsilateral stapedial reflex through immittance audiometry test which included participants 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 outcome measure, data have been reported for right and left ear separately.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 500 Hz, Right Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 500 Hz, Left Ear: Month 12 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 1000 Hz, Right Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 1000 Hz, Left Ear: Month 12 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 2000 Hz, Right Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 2000 Hz, Left Ear: Month 12 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 500 Hz, Right Ear: Month 24 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 500 Hz, Left Ear: Month 24 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 1000 Hz, Right Ear: Month 24 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 1000 Hz, Left Ear: Month 24 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 2000 Hz, Right Ear: Month 24 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 2000 Hz, Left Ear: Month 24 | 4 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 2000 Hz, Right Ear: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 500 Hz, Right Ear: Month 12 | 1 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 500 Hz, Right Ear: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 500 Hz, Left Ear: Month 12 | 1 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 1000 Hz, Left Ear: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 1000 Hz, Right Ear: Month 12 | 1 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 500 Hz, Left Ear: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 1000 Hz, Left Ear: Month 12 | 1 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 2000 Hz, Left Ear: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 2000 Hz, Right Ear: Month 12 | 1 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 1000 Hz, Right Ear: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test | 2000 Hz, Left Ear: Month 12 | 1 Participants |
Secondary
Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment
Audiological evaluations of participants were recorded and reported by transient evoked emission through otoacoustic emissions assessment which included participants with presence of transient evoked emissions from frequencies 1000 Hz to 4000 Hz at month 12 and 24. In this outcome measure, data have been reported for right and left ear separately.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1000 Hz, Right Ear: Month 12 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1000 Hz, Left Ear: Month 12 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1500 Hz, Right Ear: Month 12 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1500 Hz, Left Ear: Month 12 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 2000 Hz, Right Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 2000 Hz, Left Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 3000 Hz, Right Ear: Month 12 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 3000 Hz, Left Ear: Month 12 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 4000 Hz, Right Ear: Month 12 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 4000 Hz, Left Ear: Month 12 | 5 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1000 Hz, Right Ear: Month 24 | 3 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1000 Hz, Left Ear: Month 24 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1500 Hz, Right Ear: Month 24 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1500 Hz, Left Ear: Month 24 | 2 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 2000 Hz, Right Ear: Month 24 | 7 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 2000 Hz, Left Ear: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 3000 Hz, Right Ear: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 3000 Hz, Left Ear: Month 24 | 4 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 4000 Hz, Right Ear: Month 24 | 7 Participants |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 4000 Hz, Left Ear: Month 24 | 5 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 3000 Hz, Left Ear: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1000 Hz, Right Ear: Month 12 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1000 Hz, Right Ear: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1000 Hz, Left Ear: Month 12 | 1 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 2000 Hz, Left Ear: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1500 Hz, Right Ear: Month 12 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1000 Hz, Left Ear: Month 24 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1500 Hz, Left Ear: Month 12 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 4000 Hz, Left Ear: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 2000 Hz, Right Ear: Month 12 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1500 Hz, Right Ear: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 2000 Hz, Left Ear: Month 12 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 3000 Hz, Right Ear: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 3000 Hz, Right Ear: Month 12 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 1500 Hz, Left Ear: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 3000 Hz, Left Ear: Month 12 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 4000 Hz, Right Ear: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 4000 Hz, Right Ear: Month 12 | 2 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 2000 Hz, Right Ear: Month 24 | 3 Participants |
| Placebo | Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment | 4000 Hz, Left Ear: Month 12 | 3 Participants |
Secondary
Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test
Audiological evaluations of participants were recorded and reported by tympanometry assessment through immittance audiometry test which included participants with peak pressure signs (+) and (-) at month 12 and 24. In this outcome measure, data have been reported for right and left ear separately.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (+), Right Ear: Month 12 | 51.89 decapascals | Standard Deviation 63.024 |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (+), Left Ear: Month 12 | 5.07 decapascals | Standard Deviation 4.9 |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (+), Right Ear: Month 24 | 44.00 decapascals | Standard Deviation 46.13 |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (+), Left Ear: Month 24 | 42.71 decapascals | Standard Deviation 50.112 |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (-), Right Ear: Month 12 | 149.3 decapascals | Standard Deviation 144.34 |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (-), Left Ear: Month 12 | 79.89 decapascals | Standard Deviation 64.367 |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (-), Right Ear: Month 24 | 98.00 decapascals | Standard Deviation 55.685 |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (-), Left Ear: Month 24 | 102.2 decapascals | Standard Deviation 84.781 |
| Placebo | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (-), Left Ear: Month 24 | 135.0 decapascals | Standard Deviation 70.711 |
| Placebo | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (+), Right Ear: Month 12 | 27.33 decapascals | Standard Deviation 26.539 |
| Placebo | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (-), Right Ear: Month 12 | 67.75 decapascals | Standard Deviation 57.35 |
| Placebo | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (+), Left Ear: Month 12 | 73.75 decapascals | Standard Deviation 28.987 |
| Placebo | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (-), Right Ear: Month 24 | 83.67 decapascals | Standard Deviation 107.38 |
| Placebo | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (+), Right Ear: Month 24 | 33.50 decapascals | Standard Deviation 44.125 |
| Placebo | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (-), Left Ear: Month 12 | 46.80 decapascals | Standard Deviation 46.912 |
| Placebo | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test | Peak Pressure for Sign (+), Left Ear: Month 24 | 35.00 decapascals | Standard Deviation 46.578 |
Secondary
Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test
Audiological evaluations of participants were recorded and reported by tympanometry assessment through immittance audiometry test which included participants with static acoustic admittance at month 12 and 24. In this outcome measure, data have been reported for right and left ear separately.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test | Right Ear: Month 12 | 0.241 millimho | Standard Deviation 0.1403 |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test | Left Ear: Month 12 | 0.364 millimho | Standard Deviation 0.1513 |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test | Right Ear: Month 24 | 0.273 millimho | Standard Deviation 0.0784 |
| IV Sildenafil | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test | Left Ear: Month 24 | 0.295 millimho | Standard Deviation 0.0691 |
| Placebo | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test | Left Ear: Month 24 | 0.585 millimho | Standard Deviation 0.5558 |
| Placebo | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test | Right Ear: Month 12 | 0.403 millimho | Standard Deviation 0.1691 |
| Placebo | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test | Right Ear: Month 24 | 0.400 millimho | Standard Deviation 0.1321 |
| Placebo | Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test | Left Ear: Month 12 | 0.330 millimho | Standard Deviation 0.1595 |
Secondary
Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)
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. In this outcome measure composite scores for infants and toddlers were reported at month 12 and 24.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Sildenafil | Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Cognitive Development: Month 24 | 97.4 units on a scale | Standard Deviation 18.12 |
| IV Sildenafil | Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Language Development: Month 12 | 99.5 units on a scale | Standard Deviation 16.86 |
| IV Sildenafil | Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Cognitive Development: Month 12 | 97.5 units on a scale | Standard Deviation 16.14 |
| IV Sildenafil | Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Language Development: Month 24 | 96.7 units on a scale | Standard Deviation 21.91 |
| IV Sildenafil | Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Motor Development: Month 12 | 93.1 units on a scale | Standard Deviation 16.1 |
| IV Sildenafil | Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Motor Development: Month 24 | 99.0 units on a scale | Standard Deviation 19.59 |
| Placebo | Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Motor Development: Month 12 | 88.2 units on a scale | Standard Deviation 14.61 |
| Placebo | Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Cognitive Development: Month 24 | 97.3 units on a scale | Standard Deviation 14.95 |
| Placebo | Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Language Development: Month 24 | 95.8 units on a scale | Standard Deviation 17.7 |
| Placebo | Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Language Development: Month 12 | 94.7 units on a scale | Standard Deviation 10.25 |
| Placebo | Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Motor Development: Month 24 | 105.3 units on a scale | Standard Deviation 24 |
| Placebo | Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Cognitive Development: Month 12 | 94.5 units on a scale | Standard Deviation 14.18 |
Secondary
Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)
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. In this outcome measure composite scores for parent/caregiver were reported at month 24.
Time frame: Month 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Sildenafil | Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Social-Emotional Development | 104.5 units on a scale | Standard Deviation 21.4 |
| IV Sildenafil | Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Adaptive Behavior Development | 91.6 units on a scale | Standard Deviation 15.66 |
| Placebo | Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Social-Emotional Development | 112.5 units on a scale | Standard Deviation 18.13 |
| Placebo | Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) | Adaptive Behavior Development | 98.3 units on a scale | Standard Deviation 12.44 |
Secondary
Part B: Neurological Progress of Participants as Assessed by the Neurology Optimality Score
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.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Sildenafil | Part B: Neurological Progress of Participants as Assessed by the Neurology Optimality Score | Neurological Exam Global Score: Month 12 | 69.9 units on a scale | Standard Deviation 14.97 |
| IV Sildenafil | Part B: Neurological Progress of Participants as Assessed by the Neurology Optimality Score | Neurological Exam Global Score: Month 24 | 65.6 units on a scale | Standard Deviation 19.71 |
| Placebo | Part B: Neurological Progress of Participants as Assessed by the Neurology Optimality Score | Neurological Exam Global Score: Month 12 | 75.6 units on a scale | Standard Deviation 3.45 |
| Placebo | Part B: Neurological Progress of Participants as Assessed by the Neurology Optimality Score | Neurological Exam Global Score: Month 24 | 76.5 units on a scale | Standard Deviation 2.42 |
Secondary
Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths
An AE was any untoward medical occurrence in a participant 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.
Time frame: up to 24 months after end of study treatment in Part A (maximum up to 26 months)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths | AEs | 17 Participants |
| IV Sildenafil | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths | SAEs | 9 Participants |
| IV Sildenafil | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths | Deaths | 0 Participants |
| Placebo | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths | AEs | 17 Participants |
| Placebo | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths | SAEs | 6 Participants |
| Placebo | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths | Deaths | 2 Participants |
Secondary
Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination
Standard age-appropriate ophthalmological examinations were used to assess eye movement disorders (presence of amblyopia, strabismus, and nystagmus) at month 12 and 24. In this outcome measure, 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 outcome measure, only when there was a non-zero data for at least 1 reporting arm.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination | Strabismus Present, Right Eye: Month 24 | 1 Participants |
| IV Sildenafil | Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination | Strabismus Present, Left Eye: Month 12 | 0 Participants |
| IV Sildenafil | Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination | Strabismus Present, Left Eye: Month 24 | 1 Participants |
| IV Sildenafil | Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination | Nystagmus Present, Left Eye: Month 24 | 0 Participants |
| IV Sildenafil | Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination | Strabismus Present, Right Eye: Month 12 | 0 Participants |
| Placebo | Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination | Nystagmus Present, Left Eye: Month 24 | 1 Participants |
| Placebo | Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination | Strabismus Present, Right Eye: Month 12 | 1 Participants |
| Placebo | Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination | Strabismus Present, Left Eye: Month 12 | 1 Participants |
| Placebo | Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination | Strabismus Present, Right Eye: Month 24 | 0 Participants |
| Placebo | Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination | Strabismus Present, Left Eye: Month 24 | 0 Participants |
Secondary
Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment
Standard age-appropriate ophthalmological examinations were used to assess visual acuity (performed differently for children unable of verbal interaction) through fixates and follows (included central, steady and maintained), light perception (wince to light), no light perception, and missing at month 12 and 24. In this outcome measure, data have been reported for right and left eye separately. Rows according to visual acuity categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Fixates and Follows, Right Eye: Month 12 | 15 Participants |
| IV Sildenafil | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Light Perception, Right Eye: Month 12 | 0 Participants |
| IV Sildenafil | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Right Eye: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Fixates and Follows, Left Eye: Month 12 | 15 Participants |
| IV Sildenafil | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Light Perception, Left Eye: Month 12 | 0 Participants |
| IV Sildenafil | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Left Eye: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Fixates and Follows, Right Eye: Month 24 | 5 Participants |
| IV Sildenafil | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Right Eye: Month 24 | 7 Participants |
| IV Sildenafil | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Fixates and Follows, Left Eye: Month 24 | 5 Participants |
| IV Sildenafil | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Left Eye: Month 24 | 7 Participants |
| Placebo | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Right Eye: Month 24 | 3 Participants |
| Placebo | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Fixates and Follows, Right Eye: Month 12 | 13 Participants |
| Placebo | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Left Eye: Month 12 | 0 Participants |
| Placebo | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Light Perception, Right Eye: Month 12 | 1 Participants |
| Placebo | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Left Eye: Month 24 | 3 Participants |
| Placebo | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Right Eye: Month 12 | 0 Participants |
| Placebo | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Fixates and Follows, Right Eye: Month 24 | 9 Participants |
| Placebo | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Fixates and Follows, Left Eye: Month 12 | 13 Participants |
| Placebo | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Fixates and Follows, Left Eye: Month 24 | 9 Participants |
| Placebo | Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment | Light Perception, Left Eye: Month 12 | 1 Participants |
Secondary
Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart
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. Participants 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 participant, divided by distance at which participant was able to see/read chart without impairment; expressed as decimal, logMAR = log10 (1/decimal VA). In this outcome measure, data have been reported for right and left eye separately.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart | Right Eye: Month 12 | 0.45 LogMAR | Standard Deviation 0.394 |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart | Left Eye: Month 12 | 0.47 LogMAR | Standard Deviation 0.372 |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart | Right Eye: Month 24 | 0.20 LogMAR | Standard Deviation 0.155 |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart | Left Eye: Month 24 | 0.20 LogMAR | Standard Deviation 0.155 |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart | Left Eye: Month 24 | 0.35 LogMAR | Standard Deviation 0.409 |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart | Right Eye: Month 12 | 0.57 LogMAR | Standard Deviation 0.513 |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart | Right Eye: Month 24 | 0.28 LogMAR | Standard Deviation 0.299 |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart | Left Eye: Month 12 | 0.57 LogMAR | Standard Deviation 0.513 |
Secondary
Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment
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 outcome measure, data have been reported for right and left eye separately. Rows according to visual acuity categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | LP, Right Eye: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Left Eye: Month 12 | 13 Participants |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | VAC Quantitative, Left Eye: Month 12 | 2 Participants |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | VAC Quantitative, Right Eye: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | HM, Right Eye: Month 12 | 0 Participants |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | HM, Right Eye: Month 24 | 1 Participants |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | HM, Left Eye: Month 12 | 0 Participants |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Right Eye: Month 24 | 5 Participants |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Right Eye: Month 12 | 13 Participants |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | VAC Quantitative, Left Eye: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | LP, Left Eye: Month 12 | 1 Participants |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Left Eye: Month 24 | 6 Participants |
| IV Sildenafil | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | VAC Quantitative, Right Eye: Month 12 | 2 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Left Eye: Month 24 | 7 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | VAC Quantitative, Right Eye: Month 12 | 1 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | HM, Right Eye: Month 12 | 2 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | LP, Right Eye: Month 12 | 0 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Right Eye: Month 12 | 11 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | VAC Quantitative, Left Eye: Month 12 | 1 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | HM, Left Eye: Month 12 | 2 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | LP, Left Eye: Month 12 | 0 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Left Eye: Month 12 | 11 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | VAC Quantitative, Right Eye: Month 24 | 5 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | HM, Right Eye: Month 24 | 0 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | Missing, Right Eye: Month 24 | 7 Participants |
| Placebo | Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment | VAC Quantitative, Left Eye: Month 24 | 5 Participants |
Secondary
Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments
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 and eye movements at month 12 and 24. In this outcome measure, data have been reported for right and left eye separately. Rows according to visual status categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm.
Time frame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Population: Part B safety analysis set included all participants enrolled in Part B of the study for data analyses on developmental progress, audiological, neurological and ophthalmological assessment, and safety. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Sildenafil | Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments | Anterior Segment (Lids), Right Eye: Month 12 | 0 Participants |
| IV Sildenafil | Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments | Anterior Segment (Lids), Left Eye: Month 12 | 0 Participants |
| IV Sildenafil | Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments | Anterior Segment (Extraocular muscle movements), Right Eye: Month 24 | 1 Participants |
| IV Sildenafil | Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments | Anterior Segment (Extraocular muscle movements), Left Eye: Month 24 | 1 Participants |
| Placebo | Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments | Anterior Segment (Extraocular muscle movements), Left Eye: Month 24 | 0 Participants |
| Placebo | Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments | Anterior Segment (Lids), Right Eye: Month 12 | 1 Participants |
| Placebo | Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments | Anterior Segment (Extraocular muscle movements), Right Eye: Month 24 | 0 Participants |
| Placebo | Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments | Anterior Segment (Lids), Left Eye: Month 12 | 1 Participants |
Secondary
Percentage of Participants With Individual Components of Treatment Failure
Percentage of participants with individual components of treatment failure (need to start additional treatment targeting PPHN, need to start ECMO, or death) were evaluated. Some participants could have had multiple qualifying events for treatment failure.
Time frame: 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
Population: The ITT population included all randomized participants treated with study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IV Sildenafil | Percentage of Participants With Individual Components of Treatment Failure | Death | 6.9 percentage of participants |
| IV Sildenafil | Percentage of Participants With Individual Components of Treatment Failure | Additional Treatment Targeting PPHN | 13.8 percentage of participants |
| IV Sildenafil | Percentage of Participants With Individual Components of Treatment Failure | ECMO | 10.3 percentage of participants |
| Placebo | Percentage of Participants With Individual Components of Treatment Failure | Death | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Individual Components of Treatment Failure | Additional Treatment Targeting PPHN | 10.0 percentage of participants |
| Placebo | Percentage of Participants With Individual Components of Treatment Failure | ECMO | 10.0 percentage of participants |
Comparison: Additional Treatmentp-value: 0.706595% CI: [-15.2, 22.9]Fisher Exact
Comparison: ECMOp-value: >0.99995% CI: [-18.5, 18.5]Fisher Exact
Comparison: Deathp-value: 0.237395% CI: [-5.5, 22.8]Fisher Exact
Secondary
Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation
Time in days, from initiation of IV study drug to final weaning of mechanical ventilation among participants achieving final weaning of mechanical ventilation for PPHN was evaluated. Kaplan-Meier method was used for estimation. For participants with mechanical ventilation beyond 336 hours (14 days) from initiation of IV study drug, data was censored at 14 days.
Time frame: 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
Population: The ITT population included all randomized participants treated with study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IV Sildenafil | Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation | 8.3 days |
| Placebo | Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation | 7.3 days |
p-value: 0.9885Log Rank
Secondary
Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure
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 participants with treatment failure was evaluated. Kaplan-Meier method was used for estimation. For participants without treatment failure by the endpoint assessment date, data was censored at the endpoint assessment date.
Time frame: 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
Population: The ITT population included all randomized participants treated with study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IV Sildenafil | Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure | NA days |
| Placebo | Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure | NA days |
p-value: 0.491Log Rank
Secondary
Total Plasma Clearance (CL) of Sildenafil and Its Metabolite
CL is volume of the body fluid/ plasma from which the drug or the metabolite is completely removed per unit time. CL was obtained for Sildenafil and its major metabolite UK-103,320.
Time frame: Loading dose: prior to the start of infusion, 5, 30 minutes after end of loading infusion on Day 1; Maintenance dose: between 48 to 72, 96 to 120 hours during infusion and immediately prior to end of infusion on Day 1
Population: PK analysis set included all participants randomized and treated who had at least 1 concentration during whole treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Sildenafil | Total Plasma Clearance (CL) of Sildenafil and Its Metabolite | Sildenafil | 1.78 Liters/hour | Standard Deviation 0.89 |
| IV Sildenafil | Total Plasma Clearance (CL) of Sildenafil and Its Metabolite | UK-103,320 | 5.05 Liters/hour | Standard Deviation 2.25 |