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Trial record 27 of 66 for:    "Lung Disease" | "Bosentan"

Persistent Pulmonary Hypertension of the Newborn (FUTURE 4)

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ClinicalTrials.gov Identifier: NCT01389856
Recruitment Status : Terminated (To be compliant with the timelines as agreed with Paediatric Committee (PC) within the Paediatric Investigational Plan)
First Posted : July 8, 2011
Results First Posted : March 23, 2015
Last Update Posted : May 1, 2015
Sponsor:
Information provided by (Responsible Party):
Actelion

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Persistent Pulmonary Hypertension of the Newborn
Interventions Drug: Bosentan
Drug: Matching placebo
Enrollment 23
Recruitment Details First patient, first visit was 8 December 2011 and last patient, last visit was 5 December 2013. The investigational sites were tertiary care centers with neonatal intensive care unit facilities at which inhaled nitric oxide (iNO) was used as standard of care for persistent pulmonary hypertension of the newborn (PPHN).
Pre-assignment Details Term or near-term (gestational age > 34 weeks) hypoxic newborns with respiratory distress refractory to supplemental oxygen were considered, provided they had no significant structural cardiac anomalies documented in the pre-natal period and had no immediate need for extra corporeal membrane oxygenation (ECMO).
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Period Title: Overall Study
Started 13 [1] 8 [2]
Completed 13 8
Not Completed 0 0
[1]
Randomized and treated. An additional 2 patients were randomized but not treated.
[2]
Randomized and treated.
Arm/Group Title Bosentan Placebo Total
Hide Arm/Group Description

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Total of all reporting groups
Overall Number of Baseline Participants 13 8 21
Hide Baseline Analysis Population Description
Randomized and treated patients
Age, Continuous  
Median (Full Range)
Unit of measure:  Days
Number Analyzed 13 participants 8 participants 21 participants
1.4
(0.6 to 5.6)
1.7
(0.6 to 5.9)
1.4
(0.6 to 5.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 8 participants 21 participants
Female
9
  69.2%
6
  75.0%
15
  71.4%
Male
4
  30.8%
2
  25.0%
6
  28.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 8 participants 21 participants
Caucasian/white 11 6 17
Asian 1 0 1
Hispanic 1 1 2
Other 0 1 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 8 participants 21 participants
Czech Republic 1 1 2
France 1 0 1
Korea, Republic of 1 0 1
Poland 5 3 8
United Kingdom 4 2 6
United States 1 2 3
Gestational age  
Median (Full Range)
Unit of measure:  Weeks
Number Analyzed 13 participants 8 participants 21 participants
40.0
(36.0 to 41.0)
38.5
(36.0 to 42.0)
39.0
(36.0 to 42.0)
1.Primary Outcome
Title Percentage of Patients With Treatment Failure
Hide Description Treatment failure was defined as the need for extra corporeal membrane oxygenation or initiation of alternative pulmonary vasodilator treatment
Time Frame From baseline to up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 13 8
Measure Type: Number
Unit of Measure: percentage of participants
7.7 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Primary Outcome
Title Time to Complete Weaning From iNO
Hide Description Calculated from the time from first study drug administration to complete weaning from iNO. Weaning from iNO was considered complete if there was no requirement for the re-initiation of iNO within 24 h after stopping
Time Frame From baseline to up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 13 8
Median (95% Confidence Interval)
Unit of Measure: days
3.7
(1.17 to 6.95)
2.9
(1.26 to 4.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3407
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
3.Primary Outcome
Title Time to Complete Weaning From Mechanical Ventilation
Hide Description Calculated from the time from first study drug administration to complete weaning from mechanical ventilation
Time Frame From baseline to up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 13 8
Median (95% Confidence Interval)
Unit of Measure: days
10.8
(3.21 to 12.21)
8.6
(3.71 to 9.66)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2399
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Patients Requiring Re-initiation of iNO Therapy
Hide Description Re-initiation of iNO therapy following weaning from iNO therapy
Time Frame From baseline to up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 13 8
Measure Type: Number
Unit of Measure: percentage of participants
0 0
5.Secondary Outcome
Title Percentage of Patients With Pulmonary Hypertension (PH) at End of Treatment
Hide Description

The presence of PH was assessed by echocardiography. PH was reported as ‘present’ if at least one of the following criteria was met:

  • Shunt through ductus arteriosus was either ‘predominant right to left’ or ‘bidirectional’
  • Shunt through foramen ovale was either ‘predominant right to left’ or ‘bidirectional’
  • Marked right ventricular dilation was ticked ‘present’
  • Paradoxical shift of intraventricular septum was ticked ‘present’
  • Right ventricular systolic pressure (mmHg) was > 2/3 of the reported systemic blood pressure
Time Frame From baseline to up to 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 13 8
Measure Type: Number
Unit of Measure: percentage of participants
41.7 37.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Change in Oxygenation Index (OI) From Baseline to 3 Hours Following Study Drug Administration
Hide Description The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.
Time Frame 3 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 13 8
Median (95% Confidence Interval)
Unit of Measure: oxygenation index
Baseline
18.3
(8.2 to 35.4)
13.2
(7.9 to 39.4)
3 hours
17.3
(6.9 to 33.3)
13.0
(8.5 to 42.9)
Change from baseline
-1.6
(-5.1 to 3.3)
1.1
(-6.1 to 6.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2235
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
7.Secondary Outcome
Title Change in Oxygenation Index (OI) From Baseline to 5 Hours Following Study Drug Administration
Hide Description The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.
Time Frame 5 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 13 8
Median (95% Confidence Interval)
Unit of Measure: oxygenation index
Baseline
18.3
(8.2 to 35.4)
13.2
(7.9 to 39.4)
5 hours
16.7
(7.9 to 36.7)
13.3
(6.7 to 28.6)
Change from baseline
-0.9
(-4.7 to 4.5)
-5.6
(-7.5 to 15.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1468
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
8.Secondary Outcome
Title Change in Oxygenation Index (OI) From Baseline to 12 Hours Following Study Drug Administration
Hide Description The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 13 8
Median (95% Confidence Interval)
Unit of Measure: oxygenation index
Baseline
18.3
(8.2 to 35.4)
13.2
(7.9 to 39.4)
12 hours
14.3
(8.3 to 26.7)
11.1
(4.9 to 19.6)
Change from baseline
-0.8
(-12.9 to 2.8)
-3.9
(-14.6 to 12.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0789
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
9.Secondary Outcome
Title Change in Oxygenation Index (OI) From Baseline to 24 Hours Following Study Drug Administration
Hide Description The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 13 8
Median (95% Confidence Interval)
Unit of Measure: oxygenation index
Baseline
18.3
(8.2 to 35.4)
13.2
(7.9 to 39.4)
24 hours
13.1
(6.5 to 32.9)
11.8
(5.2 to 26.4)
Change from baseline
-4.9
(-17.0 to 1.1)
-6.9
(-9.9 to 19.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3723
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
10.Secondary Outcome
Title Change in Oxygenation Index (OI) From Baseline to 48 Hours Following Study Drug Administration
Hide Description The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients with available data
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 12 8
Median (95% Confidence Interval)
Unit of Measure: oxygenation index
Baseline
19.4
(8.2 to 35.4)
13.2
(7.9 to 39.4)
48 hours
11.5
(4.7 to 21.0)
3.8
(2.5 to 10.8)
Change from baseline
-4.9
(-15.5 to -2.1)
-9.9
(-18.0 to 3.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0569
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
11.Secondary Outcome
Title Change in Oxygenation Index (OI) From Baseline to 72 Hours Following Study Drug Administration
Hide Description The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.
Time Frame 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients with available data
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 12 8
Median (95% Confidence Interval)
Unit of Measure: oxygenation index
Baseline
19.4
(8.2 to 35.4)
13.2
(7.9 to 39.4)
72 hours
6.7
(4.2 to 17.0)
3.9
(3.7 to 10.8)
Change from baseline
-8.9
(-23.1 to -1.8)
-9.4
(-17.7 to 2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1015
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
12.Secondary Outcome
Title Change in Arterial Blood Gas (ABG) pH From Baseline to 72 Hours Following Study Drug Administration
Hide Description pH was determined in arterial blood samples at baseline and 72 h after the first study drug administration
Time Frame 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients with available data
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 12 8
Median (95% Confidence Interval)
Unit of Measure: pH
Baseline
7.37
(7.30 to 7.43)
7.31
(7.21 to 7.49)
72 hours
7.37
(7.36 to 7.43)
7.36
(7.30 to 7.39)
Change from baseline
0.04
(-0.06 to 0.07)
0.02
(-0.09 to 0.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0824
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
13.Secondary Outcome
Title Change in Arterial Blood Oxygen Saturation (SaO2) From Baseline to 72 Hours Following Study Drug Administration
Hide Description SaO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration
Time Frame 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients with available data
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 11 8
Median (95% Confidence Interval)
Unit of Measure: percentage saturation
Baseline
95.0
(92.0 to 99.0)
95.5
(89.0 to 99.0)
72 hours
98.0
(95.0 to 100.0)
97.0
(93.0 to 100.0)
Change from baseline
1.0
(0.0 to 8.0)
0.0
(-4.0 to 21.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3863
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
14.Secondary Outcome
Title Change in Partial Pressure of Oxygen (PaO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration
Hide Description PaO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration
Time Frame 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients with available data
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 12 8
Median (95% Confidence Interval)
Unit of Measure: mm Hg
Baseline
61.0
(53.0 to 132.0)
69.5
(46.0 to 111.0)
72 hours
81.0
(61.0 to 104.0)
81.5
(56.0 to 187.0)
Change from baseline
18.0
(-13.0 to 32.0)
6.0
(-12.0 to 115.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3936
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
15.Secondary Outcome
Title Change in Partial Pressure of Carbon Dioxide (PaCO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration
Hide Description PaCO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration
Time Frame 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients with available data
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 12 8
Median (95% Confidence Interval)
Unit of Measure: mm Hg
Baseline
40.5
(31.0 to 47.0)
46.0
(35.0 to 57.0)
72 hours
45.5
(36.0 to 49.0)
46.0
(41.0 to 64.0)
Change from baseline
6.0
(-1.0 to 12.0)
8.0
(-8.0 to 21.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2436
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
16.Secondary Outcome
Title Change in Pre-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration
Hide Description Simultaneous pre- (right hand) and post-ductal (lower extremities) SpO2 were measured using pulse oximetry device at baseline and 72 h after the first study drug administration
Time Frame 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients with available data
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 12 7
Median (95% Confidence Interval)
Unit of Measure: percentage saturation
Baseline
95.00
(91.00 to 99.00)
97.00
(91.00 to 99.00)
72 hours
96.00
(93.00 to 100.00)
96.00
(85.00 to 100.00)
Change from baseline
0.50
(-2.00 to 2.00)
-1.00
(-10.00 to 2.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1756
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
17.Secondary Outcome
Title Change in Post-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration
Hide Description Simultaneous pre- (right hand) and post-ductal (lower extremities) SpO2 were measured using pulse oximetry device at baseline and 72 h after the first study drug administration
Time Frame 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients with available data
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 12 8
Median (95% Confidence Interval)
Unit of Measure: percentage saturation
Baseline
96.5
(92.0 to 99.0)
96.0
(89.0 to 98.0)
72 hours
95.5
(94.0 to 99.0)
97.5
(95.0 to 100.0)
Change from baseline
0.0
(-2.0 to 3.0)
2.0
(1.0 to 12.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1155
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
18.Secondary Outcome
Title Change in Fraction of Inspired Oxygen (FiO2) From Baseline to 72 Hours Following Study Drug Administration
Hide Description FiO2 was determined according to each study centers’ standard procedure at baseline and 72 h after the first study drug administration
Time Frame 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and treated patients with available data
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 12 8
Median (95% Confidence Interval)
Unit of Measure: percentage of oxygen
Baseline
90.0
(62.0 to 97.0)
78.0
(60.0 to 100.0)
72 hours
51.5
(28.0 to 60.0)
40.0
(25.0 to 60.0)
Change from baseline
-33.5
(-50.0 to -15.0)
-35.5
(-60.0 to 0.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1400
Comments [Not Specified]
Method Non-parametric ANCOVA
Comments [Not Specified]
19.Secondary Outcome
Title Maximum Whole Blood Concentration (Cmax) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 1
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Cmax was obtained directly from the measured concentrations. Cmax was corrected to a dose of 2 mg/kg bosentan (Cmaxc). The target dose was 2 mg/kg. However, as the smallest dose unit was 8 mg (quarter of a tablet), it was not possible to achieve the exact target dose in all patients. Therefore, Cmax was divided by the actual dose (in mg/kg) and multiplied by 2 mg/kg.
Time Frame up to 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 11
Geometric Mean (95% Confidence Interval)
Unit of Measure: ng/mL
Bosentan
30.1
(2.4 to 372.2)
Ro 47-8634
0.1
(0.0 to 1.1)
Ro 48-5033
0.6
(0.0 to 18.3)
Ro 64-1056
0.9
(0.0 to 16.2)
20.Secondary Outcome
Title Cmax for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 5
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Cmax obtained directly from the measured concentrations . Cmax was corrected to a dose of 2 mg/kg bosentan (Cmaxc). The target dose was 2 mg/kg. However, as the smallest dose unit was 8 mg (quarter of a tablet), it was not possible to achieve the exact target dose in all patients. Therefore, Cmax was divided by the actual dose (in mg/kg) and multiplied by 2 mg/kg.
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 7
Geometric Mean (95% Confidence Interval)
Unit of Measure: ng/mL
Bosentan
880.0
(339.2 to 2282.7)
Ro 47-8634
24.9
(9.0 to 69.1)
Ro 48-5033
292.3
(115.8 to 738.1)
Ro 64-1056
136.0
(77.4 to 238.8)
21.Secondary Outcome
Title Time to Maximum Whole Blood Concentration (Tmax) for Bosentan on Day 1
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.
Time Frame up to 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: hours
12.0
(7.5 to 12.0)
22.Secondary Outcome
Title Tmax for Ro 47-8634 on Day 1
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.
Time Frame up to 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 5
Median (Full Range)
Unit of Measure: hours
12.0
(7.5 to 12.0)
23.Secondary Outcome
Title Tmax for Ro 48-5033 on Day 1
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.
Time Frame up to 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 7
Median (Full Range)
Unit of Measure: hours
12.0
(12.0 to 12.0)
24.Secondary Outcome
Title Tmax for Ro 64-1056 on Day 1
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.
Time Frame up to 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 8
Median (Full Range)
Unit of Measure: hours
12
(0.5 to 12.0)
25.Secondary Outcome
Title Tmax for Bosentan on Day 5
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 7
Median (Full Range)
Unit of Measure: hours
7.5
(0.8 to 12.0)
26.Secondary Outcome
Title Tmax for Ro 47-8634 on Day 5
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 7
Median (Full Range)
Unit of Measure: hours
6.5
(0.8 to 12.0)
27.Secondary Outcome
Title Tmax for Ro 48-5033 on Day 5
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 7
Median (Full Range)
Unit of Measure: hours
7.5
(0.8 to 12.0)
28.Secondary Outcome
Title Tmax for Ro 64-1056 on Day 5
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 7
Median (Full Range)
Unit of Measure: hours
12.0
(7.5 to 12.0)
29.Secondary Outcome
Title Area Under the Concentration-time Curve Over a Period of 12 h (AUC0-12 Day 1)) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 1
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUC0-12 Day 1 was calculated according to the trapezoidal rule using the measured concentration-time values above the limit of quantification.
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 11
Geometric Mean (95% Confidence Interval)
Unit of Measure: h*ng/mL
Bosentan
163.9
(9.6 to 2795.4)
Ro 47-8634
0.1
(0.0 to 3.7)
Ro 48-5033
1.4
(0.0 to 69.9)
Ro 64-1056
2.2
(0.1 to 64.1)
30.Secondary Outcome
Title Area Under the Concentration-time Curve Over a Dosing Interval at Steady State on Day 5 (AUCtau) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUCtau Day 5 was calculated according to the trapezoidal rule using the measured concentration-time values above the limit of quantification.
Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 7
Geometric Mean (95% Confidence Interval)
Unit of Measure: h*ng/mL
Bosentan
6165.4
(2429.6 to 15645.3)
Ro 47-8634
217.3
(75.3 to 626.8)
Ro 48-5033
2839.5
(1155.2 to 6979.2)
Ro 64-1056
1321.7
(729.5 to 2395.0)
31.Secondary Outcome
Title Area Under the Concentration-time Curve Over a Period of 24 h (Dose-corrected to 2 mg/kg) on Day 1 (AUC0-24C Day 1) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUC0-24C Day 1 was calculated as a multiple of AUC0-12, (2 × AUC0-12 for 2 times daily dosing) corrected to 2 mg/kg.
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 11
Geometric Mean (95% Confidence Interval)
Unit of Measure: h*ng/mL
Bosentan
287.5
(15.0 to 5504.7)
Ro 47-8634
0.1
(0.0 to 6.1)
Ro 48-5033
2.0
(0.0 to 125.8)
Ro 64-1056
3.4
(0.1 to 120.8)
32.Secondary Outcome
Title Area Under the Concentration-time Curve Over a Period of 24 h (Dose-corrected to 2 mg/kg) on Day 5 (AUC0-24C Day 5) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUC0-24C Day 5 was calculated as a multiple of AUCtau, (2 × AUCtau for 2 times daily dosing) corrected to 2 mg/kg.
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 7
Geometric Mean (95% Confidence Interval)
Unit of Measure: h*ng/mL
Bosentan
11530.2
(4507.0 to 29497.5)
Ro 47-8634
406.3
(139.8 to 1180.9)
Ro 48-5033
5310.3
(2184.4 to 12908.9)
Ro 64-1056
2471.9
(1386.1 to 4408.0)
33.Secondary Outcome
Title Accumulation Index (AI) for Bosentan
Hide Description Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Days 1 and 5. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AI was calculated as the ratio AUCtau /AUC0-12 for the subjects having PK samples collected on Day 1 and Day 5 and with AUC0-12 > 0 ng.h/mL.
Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.
Arm/Group Title Bosentan
Hide Arm/Group Description:

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Overall Number of Participants Analyzed 7
Geometric Mean (95% Confidence Interval)
Unit of Measure: accumulation index
61.6
(0.5 to 7813.9)
Time Frame Up to 21 Days, plus up to 60 days after end of treatment for serious adverse events
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bosentan Placebo
Hide Arm/Group Description

Bosentan

Bosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.

Matching placebo

Matching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

All-Cause Mortality
Bosentan Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bosentan Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   2/13 (15.38%)   3/8 (37.50%) 
Hepatobiliary disorders     
HEPATITIS  1  1/13 (7.69%)  0/8 (0.00%) 
Infections and infestations     
SEPSIS  1  0/13 (0.00%)  1/8 (12.50%) 
Metabolism and nutrition disorders     
METABOLIC ACIDOSIS  1  1/13 (7.69%)  0/8 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
HYPERCAPNIA  1  1/13 (7.69%)  0/8 (0.00%) 
PNEUMOTHORAX  1  0/13 (0.00%)  2/8 (25.00%) 
Vascular disorders     
CIRCULATORY COLLAPSE  1  1/13 (7.69%)  0/8 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bosentan Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   9/13 (69.23%)   2/8 (25.00%) 
Blood and lymphatic system disorders     
ANAEMIA  1  3/13 (23.08%)  1/8 (12.50%) 
COAGULOPATHY  1  1/13 (7.69%)  1/8 (12.50%) 
METHAEMOGLOBINAEMIA  1  1/13 (7.69%)  0/8 (0.00%) 
THROMBOCYTOPENIA  1  1/13 (7.69%)  0/8 (0.00%) 
Cardiac disorders     
MITRAL VALVE INCOMPETENCE  1  1/13 (7.69%)  0/8 (0.00%) 
Gastrointestinal disorders     
VOMITING  1  2/13 (15.38%)  0/8 (0.00%) 
GASTRIC HAEMORRHAGE  1  1/13 (7.69%)  0/8 (0.00%) 
General disorders     
GENERALISED OEDEMA  1  3/13 (23.08%)  0/8 (0.00%) 
Infections and infestations     
INFECTIOUS DISEASE CARRIER  1  1/13 (7.69%)  0/8 (0.00%) 
Injury, poisoning and procedural complications     
ENDOTRACHEAL INTUBATION COMPLICATION  1  1/13 (7.69%)  0/8 (0.00%) 
PROCEDURAL COMPLICATION  1  1/13 (7.69%)  0/8 (0.00%) 
Investigations     
BILIRUBIN CONJUGATED INCREASED  1  1/13 (7.69%)  0/8 (0.00%) 
BODY TEMPERATURE INCREASED  1  1/13 (7.69%)  0/8 (0.00%) 
C-REACTIVE PROTEIN INCREASED  1  1/13 (7.69%)  0/8 (0.00%) 
Metabolism and nutrition disorders     
HYPOGLYCAEMIA  1  0/13 (0.00%)  1/8 (12.50%) 
HYPOKALAEMIA  1  0/13 (0.00%)  1/8 (12.50%) 
HYPOPHOSPHATAEMIA  1  0/13 (0.00%)  1/8 (12.50%) 
METABOLIC ACIDOSIS  1  0/13 (0.00%)  1/8 (12.50%) 
Respiratory, thoracic and mediastinal disorders     
DYSPHONIA  1  1/13 (7.69%)  0/8 (0.00%) 
PNEUMOMEDIASTINUM  1  1/13 (7.69%)  0/8 (0.00%) 
PNEUMOTHORAX  1  1/13 (7.69%)  0/8 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pegah Nowbakht/Senior Clinical Trial Scientist
Organization: Actelion Pharmaceuticals Ltd
Phone: +41 61 565 68 41
EMail: pegah.nowbakht@actelion.com
Layout table for additonal information
Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01389856     History of Changes
Other Study ID Numbers: AC-052-391
First Submitted: June 30, 2011
First Posted: July 8, 2011
Results First Submitted: March 9, 2015
Results First Posted: March 23, 2015
Last Update Posted: May 1, 2015