Trial Outcomes & Findings for Riociguat in Children With Pulmonary Arterial Hypertension (PAH) (NCT NCT02562235)

NCT ID: NCT02562235

Last Updated: 2026-02-10

Results Overview

For each participant, one blood sample was collected at one given time point. Values below lower limit of quantification (LLOQ) were substituted by 1/2 LLOQ for the calculation in statistics. Means at any time were only calculated if at least 2/3 of the individual data were measured and were above the limit of quantification (LOQ). Geometric mean and percentage geometric coefficient of variation (%CV) are reported.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE3
• Target enrollment: 24 participants
• Primary outcome timeframe: Week 4 (pre-dose)
• Results posted on: 2026-02-10

Participant Flow

Study was conducted at multiple centers in 9 countries or regions between 29-Oct-2015 (first participant first visit) and 07-Mar-2020 (last participant last visit of main study part). The long-term extension part of the study is ongoing.

A total of 26 participants were screened. Of them, 2 participants were screening failures and 24 participants received study treatment.

Participant milestones

Measure	Riociguat >=6 to <18 Years Participants with age ≥6 to \<18 years received riociguat up to 2.5 mg three times a day (titration between 1.0 mg and 2.5 mg) for up to 8 weeks during the individual dose titration (IDT) phase, and followed with the last dose administered in the IDT phase for up to 16 weeks during the maintenance phase. Down-titration (up to 0.5 mg) of the dose for safety reasons was allowed at any time.
Overall Study STARTED	24
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure

Riociguat >=6 to <18 Years Participants with age ≥6 to \<18 years received riociguat up to 2.5 mg three times a day (titration between 1.0 mg and 2.5 mg) for up to 8 weeks during the individual dose titration (IDT) phase, and followed with the last dose administered in the IDT phase for up to 16 weeks during the maintenance phase. Down-titration (up to 0.5 mg) of the dose for safety reasons was allowed at any time.

Overall Study Adverse Event

3

Baseline Characteristics

Participants in SAF with evaluable data for this measurement

Baseline characteristics by cohort

Measure	Riociguat >=6 to <18 Years n=24 Participants Participants with age ≥6 to \<18 years received riociguat up to 2.5 mg three times a day (titration between 1.0 mg and 2.5 mg) for up to 8 weeks during the individual dose titration (IDT) phase, and followed with the last dose administered in the IDT phase for up to 16 weeks during the maintenance phase. Down-titration (up to 0.5 mg) of the dose for safety reasons was allowed at any time.
Age, Continuous	12.8 years STANDARD_DEVIATION 2.8 • n=24 Participants
Sex: Female, Male Female	11 Participants n=24 Participants
Sex: Female, Male Male	13 Participants n=24 Participants
Race/Ethnicity, Customized Not reported	24 Participants n=24 Participants
Bone age compared to chronological age Delayed	1 Participants n=24 Participants
Bone age compared to chronological age In accordance	12 Participants n=24 Participants
Bone age compared to chronological age Advanced	10 Participants n=24 Participants
Bone age compared to chronological age Missing	1 Participants n=24 Participants
WHO functional class Class I	1 Participants n=24 Participants
WHO functional class Class II	18 Participants n=24 Participants
WHO functional class Class III	5 Participants n=24 Participants
WHO functional class Class IV	0 Participants n=24 Participants
Heart rate	84.5 Beats per minute (BPM) STANDARD_DEVIATION 19.0 • n=24 Participants
Diastolic blood pressure	63.8 millimetre of mercury (mmHg) STANDARD_DEVIATION 7.9 • n=24 Participants
Systolic blood pressure	112.9 millimetre of mercury (mmHg) STANDARD_DEVIATION 10.9 • n=24 Participants
Respiratory Rate	19.6 Breath per minute STANDARD_DEVIATION 4.4 • n=21 Participants • Participants in SAF with evaluable data for this measurement
6-minute walking distance	442.12 Meter STANDARD_DEVIATION 109.67 • n=23 Participants • Participants in SAF with evaluable data for this measurement
N-terminal prohormone brain-type natriuretic peptide	982.68 Picograms per milliliter (pg/mL) STANDARD_DEVIATION 1595.77 • n=15 Participants • Participants in SAF with evaluable data for this measurement
Brain-type natriuretic peptide	10.46 Picograms per milliliter (pg/mL) STANDARD_DEVIATION 9.10 • n=7 Participants • Participants in SAF with evaluable data for this measurement
Quality of life evaluated by SF-10 questionnaire physical summary score	30.964 Scores on a scale STANDARD_DEVIATION 13.335 • n=24 Participants
Quality of life evaluated by SF-10 questionnaire psychosocial summary score	48.765 Scores on a scale STANDARD_DEVIATION 8.263 • n=24 Participants
Quality of life evaluated by PedsQL total scale score	69.77 Scores on a scale STANDARD_DEVIATION 16.29 • n=21 Participants • Participants in SAF with evaluable data for this measurement
Quality of life evaluated by PedsQL physical health summary score	64.43 Scores on a scale STANDARD_DEVIATION 15.80 • n=21 Participants • Participants in SAF with evaluable data for this measurement
Quality of life evaluated by PedsQL psychosocial health summary score	72.62 Scores on a scale STANDARD_DEVIATION 19.20 • n=21 Participants • Participants in SAF with evaluable data for this measurement
Estimate right atrial pressure	9.2 millimetre of mercury (mmHg) STANDARD_DEVIATION 2.9 • n=18 Participants • Participants in SAF with evaluable data for this measurement
Left ventricular eccentricity index	2.099 Ratio STANDARD_DEVIATION 1.275 • n=17 Participants • Participants in SAF with evaluable data for this measurement
Pulmonary artery acceleration time	91.568 Millisecond (msec) STANDARD_DEVIATION 36.853 • n=17 Participants • Participants in SAF with evaluable data for this measurement
Right ventricular cardiac index	4.343 Liter/minute/square meter (L/min/m^2) STANDARD_DEVIATION 1.599 • n=16 Participants • Participants in SAF with evaluable data for this measurement
Right ventricular cardiac output	5.511 Liter per minute (L/min) STANDARD_DEVIATION 2.093 • n=16 Participants • Participants in SAF with evaluable data for this measurement
Right atrial diastolic area	16.944 Square centimeter (cm^2) STANDARD_DEVIATION 11.071 • n=18 Participants • Participants in SAF with evaluable data for this measurement
Right atrial diastolic area index	12.788 Ratio STANDARD_DEVIATION 6.977 • n=18 Participants • Participants in SAF with evaluable data for this measurement
Right atrial systolic area	12.017 Square centimeter (cm^2) STANDARD_DEVIATION 9.391 • n=18 Participants • Participants in SAF with evaluable data for this measurement
Right atrial systolic area index	8.996 Ratio STANDARD_DEVIATION 6.021 • n=18 Participants • Participants in SAF with evaluable data for this measurement
Right ventricular fractional area change	25.7 Percentage (%) STANDARD_DEVIATION 8.5 • n=17 Participants • Participants in SAF with evaluable data for this measurement
Right ventricular diastolic area	27.155 Square centimeter (cm^2) STANDARD_DEVIATION 11.993 • n=17 Participants • Participants in SAF with evaluable data for this measurement
Right ventricular diastolic area index	20.722 Ratio STANDARD_DEVIATION 6.564 • n=17 Participants • Participants in SAF with evaluable data for this measurement
Right ventricular systolic area	20.235 Square centimeter (cm^2) STANDARD_DEVIATION 9.343 • n=17 Participants • Participants in SAF with evaluable data for this measurement
Right ventricular systolic area index	15.613 Ratio STANDARD_DEVIATION 5.745 • n=17 Participants • Participants in SAF with evaluable data for this measurement
Systolic pulmonary artery pressure	117.2 millimetre of mercury (mmHg) STANDARD_DEVIATION 51.6 • n=6 Participants • Participants in SAF with evaluable data for this measurement
Tricuspid annular plane systolic excursion	18.82 Millimeter (mm) STANDARD_DEVIATION 4.21 • n=17 Participants • Participants in SAF with evaluable data for this measurement
Tricuspid regurgitation peak velocity	4.915 Meter/second (m/s) STANDARD_DEVIATION 1.100 • n=11 Participants • Participants in SAF with evaluable data for this measurement
Pericardial effusion	1.280 Millimeter (mm) STANDARD_DEVIATION 0.212 • n=2 Participants • Participants in SAF with evaluable data for this measurement
Platelets	218.8 Giga platelets per liter STANDARD_DEVIATION 50.6 • n=24 Participants
Lymphocytes/leucocytes ratio	48.98 Percentage of leucocytes in blood STANDARD_DEVIATION 8.15 • n=24 Participants
Neutrophils/leucocytes ratio	18.71 Percentage of leucocytes in blood STANDARD_DEVIATION 10.37 • n=24 Participants
Alanine aminotransferase	18.71 Units per liter (U/L) STANDARD_DEVIATION 10.37 • n=24 Participants
Aspartate aminotransferase	23.76 Units per liter (U/L) STANDARD_DEVIATION 8.38 • n=24 Participants
Urea	25.17 microgram per deciliter (mg/dL) STANDARD_DEVIATION 7.23 • n=11 Participants • Participants in SAF with evaluable data for this measurement
Gamma glutamyl transferase	16.9 Units per liter (U/L) STANDARD_DEVIATION 14.5 • n=20 Participants • Participants in SAF with evaluable data for this measurement
Blood urea nitrogen	11.8 microgram per deciliter (mg/dL) STANDARD_DEVIATION 4.7 • n=17 Participants • Participants in SAF with evaluable data for this measurement
Estimated Glomerular Filtration Rate (eGFR)	117.877 milliliter/minute/1.73 square meter STANDARD_DEVIATION 30.649 • n=24 Participants
Sodium	140.5 millimole per Liter (mmol/L) STANDARD_DEVIATION 2.0 • n=22 Participants • Participants in SAF with evaluable data for this measurement

PRIMARY outcome

Timeframe: From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.

Population: Safety analysis set (SAF)

An adverse event (AE), including AE in relation to a medical device (i.e. Raumedic dosing pipette), is any untoward medical occurrence in a participant administered with a pharmaceutical product and does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is any untoward medical occurrence that at any dose is resulting in death, is lifethreatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity. AEs occurring between start of study drug and up to 2 days after the last dose were defined as treatment-emergent AEs (TEAEs).

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=24 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Number of Participants With Any Treatment-emergent Adverse Events Any TEAE	—	20 Participants	—	—
Number of Participants With Any Treatment-emergent Adverse Events Any serious TEAE	—	4 Participants	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Mean change in heart rate from baseline is reported.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=21 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Heart Rate From Baseline	—	4.1 Beats per minute (BPM) Standard Deviation 10.1 • Interval 10.1 to	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Mean changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline are reported.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=21 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Blood Pressure From Baseline SBP	—	-3.1 millimetre of mercury (mmHg) Standard Deviation 10.5 • Interval 10.5 to	—	—
Change in Blood Pressure From Baseline DBP	—	-2.4 millimetre of mercury (mmHg) Standard Deviation 10.0 • Interval 10.0 to	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Mean change in respiratory rate from baseline is reported.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=18 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Respiratory Rate From Baseline	—	0.3 Breath per minute Standard Deviation 3.3 • Interval 3.3 to	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

X-ray of left hand was performed for each participant and bone age was determined centrally by a specialist. For each participant, the bone age was compared to the chronological age and assigned to one of the categories - "delayed", "in accordance" or "advanced", indicating the advancement or delay in the growth of the bone. Number of participants who transitioned to another category different from baseline was calculated and is reported.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=21 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age Transitioned from Delayed to In Accordance	—	0 Participants	—	—
Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age Transitioned from Delayed to Advanced	—	0 Participants	—	—
Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age Transitioned from In Accordance to Delayed	—	1 Participants	—	—
Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age Transitioned from In Accordance to Advanced	—	3 Participants	—	—
Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age Transitioned from In Accordance to Missing	—	1 Participants	—	—
Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age Transitioned from Advanced to Delayed	—	1 Participants	—	—
Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age Transitioned from Advanced to In Accordance	—	0 Participants	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Hematology parameters were collected. Parameters with a decrease or increase in the mean value compared to baseline are reported in this data set.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=20 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Hematology Parameters (Platelets) From Baseline	—	-4.4 Giga platelets per Liter Standard Deviation 51.1 • Interval 51.1 to	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Hematology parameters were collected. Parameters with a decrease or increase in the mean value compared to baseline are reported in this data set.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=20 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Hematology Parameters (Lymphocytes/Leucocytes Ratio) From Baseline	—	-4.77 Percentage of leucocytes in blood Standard Deviation 11.08 • Interval 11.08 to	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Hematology parameters were collected. Parameters with a decrease or increase in the mean value compared to baseline are reported in this data set.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=20 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Hematology Parameter (Neutrophils/Leucocytes Ratio) From Baseline	—	5.71 Percentage of leucocytes in blood Standard Deviation 11.73 • Interval 11.73 to	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Clinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=21 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Clinical Chemistry (Alanine Aminotransferase) From Baseline	—	-1.01 Units per liter (U/L) Standard Deviation 9.86 • Interval 9.86 to	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Clinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=21 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Clinical Chemistry (Aspartate Aminotransferase) From Baseline	—	-1.94 Units per liter (U/L) Standard Deviation 6.52 • Interval 6.52 to	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Clinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=19 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Clinical Chemistry (Sodium) From Baseline	—	-1.0 millimole per Liter (mmol/L) Standard Deviation 1.9 • Interval 1.9 to	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Clinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=14 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Clinical Chemistry (Blood Urea Nitrogen) From Baseline	—	1.3 microgram per deciliter (mg/dL) Standard Deviation 4.3 • Interval 4.3 to	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Clinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set. eGFR = estimated glomerular filtration rate

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=21 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Clinical Chemistry (eGFR) From Baseline	—	-4.459 milliliter/minute/1.73 square meter Standard Deviation 25.686 • Interval 25.686 to	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Clinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=9 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Clinical Chemistry (Urea) From Baseline	—	4.06 microgram per deciliter (mg/dL) Standard Deviation 10.52 • Interval 10.52 to	—	—

PRIMARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Clinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=18 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Clinical Chemistry (Gamma Glutamyl Transferase) From Baseline	—	1.7 Units per liter (U/L) Standard Deviation 4.0 • Interval 4.0 to	—	—

PRIMARY outcome

Timeframe: Week 0 (30-90 minutes post-dose; 2.5-4 hours post-dose)

Population: Participants in safety analysis set (SAF) with evaluable data

For each participant, one blood sample was collected at one given time point. Values below lower limit of quantification (LLOQ) were substituted by 1/2 LLOQ for the calculation in statistics. Means at any time were only calculated if at least 2/3 of the individual data were measured and were above the limit of quantification (LOQ). Geometric mean and percentage geometric coefficient of variation (%CV) are reported. W = Week.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=22 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Plasma Concentration of Riociguat at Week 0 W0 (30-90 min post-dose)	—	15.340 microgram per liter (mcg/L) Geometric Coefficient of Variation 90.536	—	—
Plasma Concentration of Riociguat at Week 0 W0 (2.5-4 h post-dose)	—	17.791 microgram per liter (mcg/L) Geometric Coefficient of Variation 55.690	—	—

PRIMARY outcome

Timeframe: Week 4 (pre-dose)

Population: Participants in safety analysis set (SAF) with evaluable data

For each participant, one blood sample was collected at one given time point. Values below lower limit of quantification (LLOQ) were substituted by 1/2 LLOQ for the calculation in statistics. Means at any time were only calculated if at least 2/3 of the individual data were measured and were above the limit of quantification (LOQ). Geometric mean and percentage geometric coefficient of variation (%CV) are reported.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK n=17 Participants Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=1 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK n=2 Participants Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Plasma Concentration of Riociguat at Week 4	31.126 microgram per liter (mcg/L) Geometric Coefficient of Variation 89.790	4.510 microgram per liter (mcg/L) Geometric Coefficient of Variation NA Value was not calculated due to very low number of participants.	65.585 microgram per liter (mcg/L) Geometric Coefficient of Variation 47.727	—

PRIMARY outcome

Timeframe: Week 8 (pre-dose)

Population: Participants in safety analysis set (SAF) with evaluable data

For each participant, one blood sample was collected at one given time point. Values below lower limit of quantification (LLOQ) were substituted by 1/2 LLOQ for the calculation in statistics. Means at any time were only calculated if at least 2/3 of the individual data were measured and were above the limit of quantification (LOQ). Geometric mean and percentage geometric coefficient of variation (%CV) are reported.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK n=1 Participants Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=2 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK n=1 Participants Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK n=15 Participants Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Plasma Concentration of Riociguat at Week 8	14.000 microgram per liter (mcg/L) Geometric Coefficient of Variation NA Value was not calculated due to very low number of participants.	11.650 microgram per liter (mcg/L) Geometric Coefficient of Variation 244.238	27.100 microgram per liter (mcg/L) Geometric Coefficient of Variation NA Value was not calculated due to very low number of participants.	32.381 microgram per liter (mcg/L) Geometric Coefficient of Variation 137.719

PRIMARY outcome

Timeframe: Week 0 (30-90 minutes post-dose; 2.5-4 hours post-dose)

Population: Participants in safety analysis set (SAF) with evaluable data

BAY60-4552 is riociguat's active metabolite. For each participant, one blood sample was collected at one given time point and in that sample both riociguat and BAY60-4552 were measured. Values below lower limit of quantification (LLOQ) were substituted by 1/2 LLOQ for the calculation in statistics. Means at any time were only calculated if at least 2/3 of the individual data were measured and were above the limit of quantification (LOQ). Geometric mean and percentage geometric coefficient of variation (%CV) are reported. W = Week

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=22 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Plasma Concentration of BAY60-4552 at Week 0 W0 (30-90 min post-dose)	—	NA microgram per liter (mcg/L) Geometric Coefficient of Variation NA Value was not calculated due to very low number of participants.	—	—
Plasma Concentration of BAY60-4552 at Week 0 W0 (2.5-4 h post-dose)	—	3.922 microgram per liter (mcg/L) Geometric Coefficient of Variation 94.399	—	—

PRIMARY outcome

Timeframe: Week 4 (pre-dose)

Population: Participants in safety analysis set (SAF) with evaluable data

BAY60-4552 is riociguat's active metabolite. For each participant, one blood sample was collected at one given time point and in that sample both riociguat and BAY60-4552 were measured. Values below lower limit of quantification (LLOQ) were substituted by 1/2 LLOQ for the calculation in statistics. Means at any time were only calculated if at least 2/3 of the individual data were measured and were above the limit of quantification (LOQ). Geometric mean and percentage geometric coefficient of variation (%CV) are reported.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK n=17 Participants Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=1 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK n=2 Participants Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Plasma Concentration of BAY60-4552 at Week 4	38.579 microgram per liter (mcg/L) Geometric Coefficient of Variation 27.242	12.700 microgram per liter (mcg/L) Geometric Coefficient of Variation NA Value was not calculated due to very low number of participants.	48.822 microgram per liter (mcg/L) Geometric Coefficient of Variation 193.584	—

PRIMARY outcome

Timeframe: Week 8 (pre-dose)

Population: Participants in safety analysis set (SAF) with evaluable data

BAY60-4552 is riociguat's active metabolite. For each participant, one blood sample was collected at one given time point and in that sample both riociguat and BAY60-4552 were measured. Values below lower limit of quantification (LLOQ) were substituted by 1/2 LLOQ for the calculation in statistics. Means at any time were only calculated if at least 2/3 of the individual data were measured and were above the limit of quantification (LOQ). Geometric mean and percentage geometric coefficient of variation (%CV) are reported.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK n=1 Participants Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=2 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK n=1 Participants Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK n=15 Participants Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Plasma Concentration of BAY60-4552 at Week 8	49.600 microgram per liter (mcg/L) Geometric Coefficient of Variation NA Value was not calculated due to very low number of participants.	23.065 microgram per liter (mcg/L) Geometric Coefficient of Variation 91.296	13.200 microgram per liter (mcg/L) Geometric Coefficient of Variation NA Value was not calculated due to very low number of participants.	65.849 microgram per liter (mcg/L) Geometric Coefficient of Variation 26.864

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

6-minute walking distance (6MWD) is a exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. An increase in the distance walked indicates improvement in basic mobility.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=19 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in 6-minute Walking Distance From Baseline	—	23.01 Meter Standard Deviation 68.80 • Interval 68.8 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

The World Health Organization (WHO) functional class describes how severe a patient's pulmonary hypertension (PH) symptoms are. There are four different classes - I is the mildest and IV the most severe form of PH. Number of participants per change in number of classes is reported.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=21 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Number of Subjects With Change in WHO Functional Class From Baseline 1 classes	—	0 Participants	—	—
Number of Subjects With Change in WHO Functional Class From Baseline -3 classes	—	0 Participants	—	—
Number of Subjects With Change in WHO Functional Class From Baseline -2 classes	—	0 Participants	—	—
Number of Subjects With Change in WHO Functional Class From Baseline -1 classes	—	0 Participants	—	—
Number of Subjects With Change in WHO Functional Class From Baseline 0 classes	—	21 Participants	—	—
Number of Subjects With Change in WHO Functional Class From Baseline 2 classes	—	0 Participants	—	—
Number of Subjects With Change in WHO Functional Class From Baseline 3 classes	—	0 Participants	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Laboratory biomarkers N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) or brain-type natriuretic peptide (BNP) were tested for the participants. When both tests were available, NT-proBNP was chosen over BNP and the same test was performed at every required visit.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=14 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in NT-proBNP From Baseline	—	-65.77 picograms per milliliter (pg/mL) Standard Deviation 585.41 • Interval 585.41 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Laboratory biomarkers N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) or brain-type natriuretic peptide (BNP) were tested for the participants. When both tests were available, NT-proBNP was chosen over BNP and the same test was performed at every required visit.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=6 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in BNP From Baseline	—	7.45 Picograms per milliliter (pg/mL) Standard Deviation 10.65 • Interval 10.65 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

SF-10 is a parent-completed health survey for children that contains 10 questions adapted from the Child Health Questionnaire. It is scored using nom-based scoring to produce physical and psychosocial health summary measures. The possible range for the physical measure is -10.9 to 57.2 scores and the possible range for the psychosocial measure is 8.8 to 62.3 scores. Higher scores indicate more favorable functioning.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=21 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Quality of Life Evaluated by SF-10 Questionnaire From Baseline Physical summary score	—	5.79 Scores on a scale Standard Deviation 12.46 • Interval 12.46 to	—	—
Change in Quality of Life Evaluated by SF-10 Questionnaire From Baseline Psychosocial summary score	—	1.10 Scores on a scale Standard Deviation 6.85 • Interval 6.85 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

The PedsQL Generic Core Scales were designed to measure health-related quality of life in children and adolescents. It has 4 dimensions: physical functioning, emotional functioning, social functioning and school functioning. 3 Summary Scores of PedsQL were calculated from the scales including total scale score (23 questions), physical health summary score (physical functioning, 8 questions) and psychosocial health summary score (emotional, social and school functioning, 15 questions). Responses of the questions are transformed to a 0-100 scale. Higher scores indicate better quality of life.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=19 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Quality of Life Evaluated by PedsQL Scale Total scale score	—	3.49 Scores on a scale Standard Deviation 10.81 • Interval 10.81 to	—	—
Change in Quality of Life Evaluated by PedsQL Scale Physical health summary score	—	4.28 Scores on a scale Standard Deviation 13.51 • Interval 13.51 to	—	—
Change in Quality of Life Evaluated by PedsQL Scale Psychosocial health summary score	—	3.07 Scores on a scale Standard Deviation 11.21 • Interval 11.21 to	—	—

SECONDARY outcome

Timeframe: Up to Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Clinical worsening was defined as: hospitalization for right heart failure, death, lung transplantation, Pott's anastomosis and atrioseptostomy, worsening of pulmonary arterial hypertension (PAH) symptoms, which must include either an increase in World Health Organization (WHO) functional class or appearance/worsening symptoms of right heart failure and need for additional PAH therapy.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=24 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Number of Subjects With Clinical Worsening	—	2 Participants	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Estimated right atrial pressure was measured by echocardiography.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=16 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Estimated Right Atrial Pressure From Baseline	—	-0.6 millimetre of mercury (mmHg) Standard Deviation 3.6 • Interval 3.6 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Left ventricular (LV) eccentricity index (EI) was measured by echocardiography and defined as the ratio of the LV anteroposterior dimension to the septolateral dimension in the parasternal short-axis window by echocardiography. The value of EI greater than 1.0 is abnormal and suggests right ventricle (RV) overload.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=15 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Left Ventricular Eccentricity Index From Baseline	—	0.002 Ratio Standard Deviation 0.907 • Interval 0.907 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Pericardial effusion was measured by echocardiography.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=1 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Pericardial Effusion From Baseline	—	1.040 Millimeter (mm) Standard Deviation NA Value was not calculated due to very low number of participants.	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Pulmonary artery acceleration time was measured by echocardiography.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=15 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Pulmonary Artery Acceleration Time From Baseline	—	-7.777 Millisecond (msec) Standard Deviation 35.898 • Interval 35.898 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Right ventricle (RV) cardiac index (CI) was measured by echocardiography and calculated by dividing the cardiac output (stroke volume × heart rate) by the body surface area. The change in RV CI should not be understood solely but associated with other conditions of the participants.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=13 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Right Ventricular Cardiac Index From Baseline	—	0.188 Liter/minute/square meter (L/min/m^2) Standard Deviation 2.094 • Interval 2.094 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Right ventricular cardiac output was measured by echocardiography.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=13 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Right Ventricular Cardiac Output From Baseline	—	0.457 Liter per minute (L/min) Standard Deviation 3.066 • Interval 3.066 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Right atrial diastolic area was measured by echocardiography.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=16 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Right Atrial Diastolic Area From Baseline	—	1.078 Square centimeter (cm^2) Standard Deviation 3.330 • Interval 3.33 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Right atrial (RA) diastolic area index was measured by echocardiography and calculated by dividing the RA area at end-diastole by the body surface area. The RA area index is a reflection of RA volume at end-diastole. The change in the index should not be understood solely but associated with other conditions of the participants.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=16 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Right Atrial Diastolic Area Index From Baseline	—	0.643 Ratio Standard Deviation 2.314 • Interval 2.314 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Right atrial systolic area was measured by echocardiography.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=16 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Right Atrial Systolic Area From Baseline	—	0.424 Square centimeter (cm^2) Standard Deviation 3.758 • Interval 3.758 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Right atrial (RA) systolic area index was measured by echocardiography and calculated by dividing the RA area at end-systole by the body surface area. The RA area index is a reflection of RA volume at end-systole. The change in the index should not be understood solely but associated with other conditions of the participants.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=16 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Right Atrial Systolic Area Index From Baseline	—	0.329 Ratio Standard Deviation 2.417 • Interval 2.417 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Right ventricular fractional area change was measured by echocardiography.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=15 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Right Ventricular Fractional Area Change From Baseline	—	-4.3 Percentage (%) of area Standard Deviation 7.3 • Interval 7.3 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Right ventricular diastolic area was measured by echocardiography.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=15 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Right Ventricular Diastolic Area From Baseline	—	0.618 Square centimeter (cm^2) Standard Deviation 4.519 • Interval 4.519 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Right ventricular (RV) diastolic area index was measured by echocardiography and calculated by dividing the RV area at end-diastole by the body surface area. The RV area index is a reflection of RV volume at end-diastole. The change in the index should not be understood solely but associated with other conditions of the participants.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=15 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Right Ventricular Diastolic Area Index From Baseline	—	0.451 Ratio Standard Deviation 3.562 • Interval 3.562 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Right ventricular systolic area was measured by echocardiography.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=15 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Right Ventricular Systolic Area From Baseline	—	1.725 Square centimeter (cm^2) Standard Deviation 3.847 • Interval 3.847 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Right ventricular (RV) systolic area index was measured by echocardiography and calculated by dividing the RV area at end-systole by the body surface area. The RV area index is a reflection of RV volume at end-systole. The change in the index should not be understood solely but associated with other conditions of the participants.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=15 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Right Ventricular Systolic Area Index From Baseline	—	1.244 Ratio Standard Deviation 3.277 • Interval 3.277 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Systolic pulmonary artery pressure was measured by echocardiography.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=3 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Systolic Pulmonary Artery Pressure From Baseline	—	5.7 millimetre of mercury (mmHg) Standard Deviation 49.0 • Interval 49.0 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Tricuspid annular plane systolic excursion (TAPSE) was measured by echocardiography.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=15 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Tricuspid Annular Plane Systolic Excursion From Baseline	—	-1.27 Millimeter (mm) Standard Deviation 3.87 • Interval 3.87 to	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

Tricuspid regurgitation peak velocity was measured by echocardiography.

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=10 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Change in Tricuspid Regurgitation Peak Velocity From Baseline	—	-0.085 Meter/second (m/s) Standard Deviation 0.726 • Interval 0.726 to	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: At the beginning of the treatment (Week 0)

Population: Participants in safety analysis set (SAF) with evaluable data

To assess the taste and texture of oral suspension of Riociguat, a questionnaire including 7 questions was used. Responses to Questions 1 to 4 are reported in this endpoint. Questions 1 and 2 were asked before the participants received the suspension; whereas questions 3 and 4 were asked right after administration of the suspension. Participants were asked to respond to the 4 questions as "yes" (= positive answer), "I do not know/unsure"(= indifferent answer) or "No" (= negative answer).

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=16 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like the look of the drink · Yes	—	4 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like the look of the drink · No	—	2 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like the look of the drink · Unsure	—	9 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like the look of the drink · Missing	—	1 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like the smell of the drink · Yes	—	4 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like the smell of the drink · No	—	2 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like the smell of the drink · Unsure	—	9 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like the smell of the drink · Missing	—	1 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like the drink · Yes	—	9 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like the drink · No	—	1 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like the drink · Unsure	—	5 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like the drink · Missing	—	1 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like to drink again · Yes	—	12 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like to drink again · No	—	0 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like to drink again · Unsure	—	3 Participants	—	—
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 Like to drink again · Missing	—	1 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

To assess the taste and texture of oral suspension of Riociguat, a questionnaire including 7 questions was used. Responses to Questions 1 to 4 are reported in this endpoint. Questions 1 and 2 were asked before the participants received the suspension; whereas questions 3 and 4 were asked right after administration of the suspension. Participants were asked to respond to the 4 questions as "yes" (= positive answer), "I do not know/unsure"(= indifferent answer) or "No" (= negative answer).

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=14 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like the look of the drink · Yes	—	6 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like the look of the drink · No	—	1 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like the look of the drink · Unsure	—	6 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like the look of the drink · Missing	—	1 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like the smell of the drink · Yes	—	7 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like the smell of the drink · No	—	2 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like the smell of the drink · Unsure	—	4 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like the smell of the drink · Missing	—	1 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like the drink · Yes	—	6 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like the drink · No	—	4 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like the drink · Unsure	—	3 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like the drink · Missing	—	1 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like to drink again · Yes	—	6 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like to drink again · No	—	3 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like to drink again · Unsure	—	4 Participants	—	—
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 Like to drink again · Missing	—	1 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: At the beginning of the treatment (Week 0)

Population: Participants in safety analysis set (SAF) with evaluable data

To assess the taste and texture of oral suspension of Riociguat, a questionnaire including 7 questions was used. Number of participants per responses to Questions 5 "Taste of the drink" is reported in this endpoint. Question 5 was only asked to participants who answered "No" to Question 3 "Did you like the drink" or Question 4 "Would you like to drink this again". Participants were asked to answer "yes", "I do not know/unsure" or "No" to each taste including "sweet, sour, bitter, salty, disgusting and fruity".

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=1 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Sweet · Yes	—	1 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Sweet · No	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Sweet · Unsure	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Sour · Yes	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Sour · No	—	1 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Sour · Unsure	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Bitter · Yes	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Bitter · No	—	1 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Bitter · Unsure	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Salty · Yes	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Salty · No	—	1 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Salty · Unsure	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Disgusting · Yes	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Disgusting · No	—	1 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Disgusting · Unsure	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Fruity · Yes	—	1 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Fruity · No	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 Fruity · Unsure	—	0 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with evaluable data

To assess the taste and texture of oral suspension of Riociguat, a questionnaire including 7 questions was used. Number of participants per responses to Questions 5 "Taste of the drink" is reported in this endpoint. Question 5 was only asked to participants who answered "No" to Question 3 "Did you like the drink" or Question 4 "Would you like to drink this again". Participants were asked to answer "yes", "I do not know/unsure" or "No" to each taste including "sweet, sour, bitter, salty, disgusting and fruity".

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=4 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Sweet · Yes	—	2 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Sweet · No	—	1 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Sweet · Unsure	—	1 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Sour · Yes	—	1 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Sour · No	—	3 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Sour · Unsure	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Bitter · Yes	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Bitter · No	—	3 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Bitter · Unsure	—	1 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Salty · Yes	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Salty · No	—	4 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Salty · Unsure	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Disgusting · Yes	—	4 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Disgusting · No	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Disgusting · Unsure	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Fruity · Yes	—	0 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Fruity · No	—	2 Participants	—	—
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 Fruity · Unsure	—	2 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: At the beginning of the treatment (Week 0)

Population: Participants in safety analysis set (SAF) with evaluable data

To assess the taste and texture of oral suspension of Riociguat, a questionnaire including 7 questions was used. Number of participants per responses to Questions 6 "Drink feels in mouth" is reported in this endpoint. Question 6 was only asked to participants who answered "No" to Question 3 "Did you like the drink" or Question 4 "Would you like to drink this again". Participants were asked to answer "yes", "I do not know/unsure" or "No" to each feeling including "like sand, sticky, gooey, slimy, creamy".

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=1 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Like Sand · Yes	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Like Sand · No	—	1 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Like Sand · Unsure	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Sticky · Yes	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Sticky · No	—	1 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Sticky · Unsure	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Gooey · Yes	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Gooey · No	—	1 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Gooey · Unsure	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Slimy · Yes	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Slimy · No	—	1 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Slimy · Unsure	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Creamy · Yes	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Creamy · No	—	1 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 Creamy · Unsure	—	0 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with assessment

To assess the taste and texture of oral suspension of Riociguat, a questionnaire including 7 questions was used. Number of participants per responses to Questions 6 "Drink feels in mouth" is reported in this endpoint. Question 6 was only asked to participants who answered "No" to Question 3 "Did you like the drink" or Question 4 "Would you like to drink this again". Participants were asked to answer "yes", "I do not know/unsure" or "No" to each feeling including "like sand, sticky, gooey, slimy, creamy".

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=4 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Like sand · Yes	—	3 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Like sand · No	—	1 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Like sand · Unsure	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Sticky · Yes	—	1 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Sticky · No	—	3 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Sticky · Unsure	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Gooey · Yes	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Gooey · No	—	3 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Gooey · Unsure	—	1 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Slimy · Yes	—	2 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Slimy · No	—	1 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Slimy · Unsure	—	1 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Creamy · Yes	—	0 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Creamy · No	—	2 Participants	—	—
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 Creamy · Unsure	—	2 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: At the beginning of the treatment (Week 0)

Population: Participants in safety analysis set (SAF) with assessment

To assess the taste and texture of oral suspension of Riociguat, a questionnaire including 7 questions was used. Number of participants per responses to Questions 7 "Did you like the taste after swallowing" is reported in this endpoint. Question 7 was only asked to participants who answered "No" to Question 3 "Did you like the drink" or Question 4 "Would you like to drink this again". Participants were asked to respond as "yes" (= positive answer), "I do not know/unsure"(= indifferent answer) or "No" (= negative answer).

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=1 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 0 Like the taste after swallowing - Yes	—	1 Participants	—	—
Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 0 Like the taste after swallowing - No	—	0 Participants	—	—
Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 0 Like the taste after swallowing - Unsure	—	0 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with assessment

To assess the taste and texture of oral suspension of Riociguat, a questionnaire including 7 questions was used. Number of participants per responses to Questions 7 "Did you like the taste after swallowing" is reported in this endpoint. Question 7 was only asked to participants who answered "No" to Question 3 "Did you like the drink" or Question 4 "Would you like to drink this again". Participants were asked to respond as "yes" (= positive answer), "I do not know/unsure"(= indifferent answer) or "No" (= negative answer).

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=4 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 24 Like the taste after swallowing - Yes	—	0 Participants	—	—
Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 24 Like the taste after swallowing - No	—	3 Participants	—	—
Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 24 Like the taste after swallowing - Unsure	—	1 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: At the beginning of the treatment (Week 0)

Population: Participants in safety analysis set (SAF) with assessment

The facial expression of the subjects concerning appearance, smell and taste of the suspension of Riociguat was captured by the investigators as "comfortable", "indifferent" and "displeased".

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=16 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 0 Comfortable	—	7 Participants	—	—
Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 0 Indifferent	—	8 Participants	—	—
Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 0 Displeased	—	0 Participants	—	—
Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 0 Missing	—	1 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 24 (plus/minus 5 days)

Population: Participants in safety analysis set (SAF) with assessment

The facial expression of the subjects concerning appearance, smell and taste of the suspension of Riociguat was captured by the investigators as "comfortable", "indifferent" and "displeased".

Outcome measures

Measure	Riociguat 2.0 mg or Equivalent - PK Participants who received riociguat at 2.0 mg or body weight-adjusted dose equivalent to the exposure of 2.0 mg dose in adults at the day of PK measurement	Riociguat 0.5 mg or Equivalent - PK n=14 Participants Participants who received riociguat at 0.5 mg or body weight-adjusted dose equivalent to the exposure of 0.5 mg dose in adults at the day of PK measurement	Riociguat 1.0 mg or Equivalent - PK Participants who received riociguat at 1.0 mg or body weight-adjusted dose equivalent to the exposure of 1.0 mg dose in adults at the day of PK measurement	Riociguat 2.5 mg or Equivalent - PK Participants who received riociguat at 2.5 mg or body weight-adjusted dose equivalent to the exposure of 2.5 mg dose in adults at the day of PK measurement
Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 24 Comfortable	—	6 Participants	—	—
Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 24 Indifferent	—	5 Participants	—	—
Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 24 Displeased	—	2 Participants	—	—
Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 24 Missing	—	1 Participants	—	—

Adverse Events

Riociguat >=6 to <18 Years

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Riociguat >=6 to <18 Years n=24 participants at risk Participants with age ≥6 to \<18 years received riociguat up to 2.5 mg three times a day (titration between 1.0 mg and 2.5 mg) for up to 8 weeks during the individual dose titration (IDT) phase, and followed with the last dose administered in the IDT phase for up to 16 weeks during the maintenance phase. Down-titration (up to 0.5 mg) of the dose for safety reasons was allowed at any time.
Skin and subcutaneous tissue disorders Pain of skin	4.2% 1/24 • Number of events 1 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.
Skin and subcutaneous tissue disorders Skin swelling	4.2% 1/24 • Number of events 1 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.
Vascular disorders Hypotension	4.2% 1/24 • Number of events 1 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.
Cardiac disorders Right ventricular failure	8.3% 2/24 • Number of events 2 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.
Infections and infestations Vascular device infection	4.2% 1/24 • Number of events 1 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.
Respiratory, thoracic and mediastinal disorders Asthma	4.2% 1/24 • Number of events 2 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.

Other adverse events

Measure	Riociguat >=6 to <18 Years n=24 participants at risk Participants with age ≥6 to \<18 years received riociguat up to 2.5 mg three times a day (titration between 1.0 mg and 2.5 mg) for up to 8 weeks during the individual dose titration (IDT) phase, and followed with the last dose administered in the IDT phase for up to 16 weeks during the maintenance phase. Down-titration (up to 0.5 mg) of the dose for safety reasons was allowed at any time.
Infections and infestations Upper respiratory tract infection	16.7% 4/24 • Number of events 4 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.
Nervous system disorders Dizziness	8.3% 2/24 • Number of events 2 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.
Nervous system disorders Headache	29.2% 7/24 • Number of events 11 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.
Vascular disorders Hypotension	8.3% 2/24 • Number of events 4 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.
Gastrointestinal disorders Abdominal pain	16.7% 4/24 • Number of events 5 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.
General disorders Pyrexia	12.5% 3/24 • Number of events 3 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.
Infections and infestations Gastroenteritis	8.3% 2/24 • Number of events 2 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.
Infections and infestations Nasopharyngitis	16.7% 4/24 • Number of events 7 • From start of study drug up to 2 days after the last dose of study drug in the main study part, up to 24 weeks plus/minus 5 days.

Additional Information

Therapeutic Area Head

Bayer

Phone: 1-888-8422937

Email: clinical-trials-contact@bayer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Most restricted agreement: CTA Japan; Embargo time mentioned. Hospital shall obtain prior written consent of Sponsor if PI intends to publish the information obtained from study externally such as in a professional society or association.
• Publication restrictions are in place

Restriction type: OTHER