Hypertension, Pulmonary
Conditions
Keywords
Pulmonary arterial hypertension
Brief summary
This study was designed to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of riociguat at age-, sex- and body-weight-adjusted doses of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID in children from ≥6 to less than 18 years with pulmonary arterial hypertension (PAH) group 1. The study design consisted of a main study part followed by an optional long-term extension part. The main treatment period consisted of two phases: titration phase up to 8 weeks and a maintenance phase up to 16 weeks.
Interventions
DRUGRiociguat (Adempas, BAY63-2521)
For children with body-weight \<50 kg at screening: body-weight adjusted dose equivalent to the exposure of (0.5 mg) 1.0 - 2.5 mg three times a day, IDT in adults treated for PAH; oral suspension. For children ≥50 kg at screening: 1.0 to 2.5 mg three times a day; oral tablet.
Sponsors
Bayer
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Children from 6 years to less than 18 years of age with pulmonary arterial hypertension (PAH) * Diagnosed with PAH : * Idiopathic (IPAH) * Hereditable (HPAH) * PAH associated with (APAH) * Connective tissue disease * Congenital heart disease with shunt closure more than 6 months ago (no open shunts, confirmed by RHC no less than 4 months after surgery) Regardless of the type of PAH, the following findings are not exclusionary: \--- Patent foramen ovale (PFO) and asymptomatic, isolated, ostium secundum atrial septal defect (OS-ASD) ≤ 1 cm (both confirmed by echocardiogram) and not associated with hemodynamic alterations indicative of significant shunt, e.g. Qp/Qs ratio less \<1.5:1 are not exclusionary * PAH diagnosed by right heart catheterization (RHC) at any time prior to enrolment (for patients with closed shunts - RHC no less than 4 months after surgery) * PAH confirmed by a RHC at any time prior to start of study, with mean pulmonary artery pressure (PAPmean) ≥25 mmHg at rest, pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) ≤15 mmHg, and pulmonary vascular resistance (PVR) \>240 dyn•sec•cm\^-5 (i.e., ≥3.0 wood units•m\^2) * Patients must be on standard of care PAH medications, allowing Endothelin Receptor Antagonists (ERA) and/or Prostacyclin Analogues (PCA), for at least 12 weeks prior to baseline visit. Two groups of patients will be included: * Prevalent: Patients currently on PAH medication (allowing ERA and/or PCA) who need additional treatment (discretion of the investigator) * Incident: Treatment naïve patients initiated on PAH medication (allowing ERA and /or PCA) and then riociguat added once patients are stable on standard of care * WHO functional class I-III * Adolescent females of childbearing potential can only be included in the study if a pregnancy test is negative. Adolescent females of childbearing potential must agree to receive sexual counseling and use effective contraception as applicable. 'Effective contraception' is defined as progestogen-only hormonal contraception associated with inhibition of ovulation (implant), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), or any combination of adequate methods of birth control (e.g. condoms with hormonal contraception). Agreement to use contraception is required from the signing of the informed consent form up until 4 weeks after the last study drug administration. * Young men must agree to use adequate contraception when sexually active. * Written inform consent provided and if applicable child assent provided
Exclusion criteria
* Concomitant use of the following medications: phosphodiesterase (PDE) 5 inhibitors (such as sildenafil, tadalafil, vardenafil) and non-specific phosphodiesterase (PDE) inhibitors (theophylline, dipyridamole), nitrates or NO donors (such as amyl nitrite) in any form \-- Pretreatment with NO donors (e.g. nitrates) within the last 2-weeks before visit 1. The use of any drug including NO acutely for testing during catheterization is not an exclusion criterion. * Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization or any history of bronchial artery embolization or massive hemoptysis within 3 months prior to screening * Systolic blood pressure (SBP) more than 5 mmHg lower than the age-, sex- and height-adapted level of the 50th SBP percentile (NHBPEP, 2004) * History of left-sided heart disease, including valvular disease or heart failure * Pulmonary hypertension related to conditions other than specified in the inclusion criteria * WHO functional class IV * Pulmonary veno-occlusive disease * Screening aspartate transaminase (AST) and/ or alanine transaminase (ALT) more than 3 times the upper limit of normal (ULN) * Severe restrictive lung disease * Severe congenital abnormalities of the lung, thorax, and diaphragm * Clinically relevant hepatic dysfunction (especially Child Pugh C) * Renal insufficiency (estimated glomerular filtration rate \<30 mL/min/1.73m\^2 e.g. calculated based on Schwartz formula) * PH associated with idiopathic interstitial pneumonia (PH-IIP)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration of BAY60-4552 at Week 4 | Week 4 (pre-dose) | 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. |
| Plasma Concentration of BAY60-4552 at Week 8 | Week 8 (pre-dose) | 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. |
| Number of Participants With Any Treatment-emergent Adverse Events | 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. | 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). |
| Change in Heart Rate From Baseline | Baseline and Week 24 (plus/minus 5 days) | Mean change in heart rate from baseline is reported. |
| Change in Blood Pressure From Baseline | Baseline and Week 24 (plus/minus 5 days) | Mean changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline are reported. |
| Change in Respiratory Rate From Baseline | Baseline and Week 24 (plus/minus 5 days) | Mean change in respiratory rate from baseline is reported. |
| Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in Hematology Parameters (Platelets) From Baseline | Baseline and Week 24 (plus/minus 5 days) | Hematology parameters were collected. Parameters with a decrease or increase in the mean value compared to baseline are reported in this data set. |
| Change in Hematology Parameters (Lymphocytes/Leucocytes Ratio) From Baseline | Baseline and Week 24 (plus/minus 5 days) | Hematology parameters were collected. Parameters with a decrease or increase in the mean value compared to baseline are reported in this data set. |
| Change in Hematology Parameter (Neutrophils/Leucocytes Ratio) From Baseline | Baseline and Week 24 (plus/minus 5 days) | Hematology parameters were collected. Parameters with a decrease or increase in the mean value compared to baseline are reported in this data set. |
| Change in Clinical Chemistry (Alanine Aminotransferase) From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in Clinical Chemistry (Aspartate Aminotransferase) From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in Clinical Chemistry (Sodium) From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in Clinical Chemistry (Blood Urea Nitrogen) From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in Clinical Chemistry (eGFR) From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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 |
| Change in Clinical Chemistry (Urea) From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in Clinical Chemistry (Gamma Glutamyl Transferase) From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Plasma Concentration of Riociguat at Week 0 | Week 0 (30-90 minutes post-dose; 2.5-4 hours post-dose) | 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. |
| Plasma Concentration of Riociguat at Week 4 | Week 4 (pre-dose) | 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. |
| Plasma Concentration of Riociguat at Week 8 | Week 8 (pre-dose) | 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. |
| Plasma Concentration of BAY60-4552 at Week 0 | Week 0 (30-90 minutes post-dose; 2.5-4 hours post-dose) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Right Ventricular Systolic Area From Baseline | Baseline and Week 24 (plus/minus 5 days) | Right ventricular systolic area was measured by echocardiography. |
| Change in Systolic Pulmonary Artery Pressure From Baseline | Baseline and Week 24 (plus/minus 5 days) | Systolic pulmonary artery pressure was measured by echocardiography. |
| Change in Tricuspid Annular Plane Systolic Excursion From Baseline | Baseline and Week 24 (plus/minus 5 days) | Tricuspid annular plane systolic excursion (TAPSE) was measured by echocardiography. |
| Change in Tricuspid Regurgitation Peak Velocity From Baseline | Baseline and Week 24 (plus/minus 5 days) | Tricuspid regurgitation peak velocity was measured by echocardiography. |
| Change in Right Ventricular Systolic Area Index From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in 6-minute Walking Distance From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Number of Subjects With Change in WHO Functional Class From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in NT-proBNP From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in BNP From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in Quality of Life Evaluated by SF-10 Questionnaire From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in Quality of Life Evaluated by PedsQL Scale | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Number of Subjects With Clinical Worsening | Up to Week 24 (plus/minus 5 days) | 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. |
| Change in Estimated Right Atrial Pressure From Baseline | Baseline and Week 24 (plus/minus 5 days) | Estimated right atrial pressure was measured by echocardiography. |
| Change in Left Ventricular Eccentricity Index From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in Pericardial Effusion From Baseline | Baseline and Week 24 (plus/minus 5 days) | Pericardial effusion was measured by echocardiography. |
| Change in Pulmonary Artery Acceleration Time From Baseline | Baseline and Week 24 (plus/minus 5 days) | Pulmonary artery acceleration time was measured by echocardiography. |
| Change in Right Ventricular Cardiac Index From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in Right Ventricular Cardiac Output From Baseline | Baseline and Week 24 (plus/minus 5 days) | Right ventricular cardiac output was measured by echocardiography. |
| Change in Right Atrial Diastolic Area From Baseline | Baseline and Week 24 (plus/minus 5 days) | Right atrial diastolic area was measured by echocardiography. |
| Change in Right Atrial Diastolic Area Index From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in Right Atrial Systolic Area From Baseline | Baseline and Week 24 (plus/minus 5 days) | Right atrial systolic area was measured by echocardiography. |
| Change in Right Atrial Systolic Area Index From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
| Change in Right Ventricular Fractional Area Change From Baseline | Baseline and Week 24 (plus/minus 5 days) | Right ventricular fractional area change was measured by echocardiography. |
| Change in Right Ventricular Diastolic Area From Baseline | Baseline and Week 24 (plus/minus 5 days) | Right ventricular diastolic area was measured by echocardiography. |
| Change in Right Ventricular Diastolic Area Index From Baseline | Baseline and Week 24 (plus/minus 5 days) | 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. |
Countries
Colombia, Germany, Hungary, Italy, Japan, Mexico, Poland, Taiwan, Turkey (Türkiye)
Contacts
STUDY_DIRECTORBayer Study Director
Bayer
Participant flow
Recruitment details
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.
Pre-assignment details
A total of 26 participants were screened. Of them, 2 participants were screening failures and 24 participants received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Riociguat >=6 to <18 Years |
|---|---|
| 6-minute walking distance | 442.12 Meter STANDARD_DEVIATION 109.67 |
| Age, Continuous | 12.8 years STANDARD_DEVIATION 2.8 |
| Alanine aminotransferase | 18.71 Units per liter (U/L) STANDARD_DEVIATION 10.37 |
| Aspartate aminotransferase | 23.76 Units per liter (U/L) STANDARD_DEVIATION 8.38 |
| Blood urea nitrogen | 11.8 microgram per deciliter (mg/dL) STANDARD_DEVIATION 4.7 |
| Bone age compared to chronological age Advanced | 10 Participants |
| Bone age compared to chronological age Delayed | 1 Participants |
| Bone age compared to chronological age In accordance | 12 Participants |
| Bone age compared to chronological age Missing | 1 Participants |
| Brain-type natriuretic peptide | 10.46 Picograms per milliliter (pg/mL) STANDARD_DEVIATION 9.1 |
| Diastolic blood pressure | 63.8 millimetre of mercury (mmHg) STANDARD_DEVIATION 7.9 |
| Estimated Glomerular Filtration Rate (eGFR) | 117.877 milliliter/minute/1.73 square meter STANDARD_DEVIATION 30.649 |
| Estimate right atrial pressure | 9.2 millimetre of mercury (mmHg) STANDARD_DEVIATION 2.9 |
| Gamma glutamyl transferase | 16.9 Units per liter (U/L) STANDARD_DEVIATION 14.5 |
| Heart rate | 84.5 Beats per minute (BPM) STANDARD_DEVIATION 19 |
| Left ventricular eccentricity index | 2.099 Ratio STANDARD_DEVIATION 1.275 |
| Lymphocytes/leucocytes ratio | 48.98 Percentage of leucocytes in blood STANDARD_DEVIATION 8.15 |
| Neutrophils/leucocytes ratio | 18.71 Percentage of leucocytes in blood STANDARD_DEVIATION 10.37 |
| N-terminal prohormone brain-type natriuretic peptide | 982.68 Picograms per milliliter (pg/mL) STANDARD_DEVIATION 1595.77 |
| Pericardial effusion | 1.280 Millimeter (mm) STANDARD_DEVIATION 0.212 |
| Platelets | 218.8 Giga platelets per liter STANDARD_DEVIATION 50.6 |
| Pulmonary artery acceleration time | 91.568 Millisecond (msec) STANDARD_DEVIATION 36.853 |
| Quality of life evaluated by PedsQL physical health summary score | 64.43 Scores on a scale STANDARD_DEVIATION 15.8 |
| Quality of life evaluated by PedsQL psychosocial health summary score | 72.62 Scores on a scale STANDARD_DEVIATION 19.2 |
| Quality of life evaluated by PedsQL total scale score | 69.77 Scores on a scale STANDARD_DEVIATION 16.29 |
| Quality of life evaluated by SF-10 questionnaire physical summary score | 30.964 Scores on a scale STANDARD_DEVIATION 13.335 |
| Quality of life evaluated by SF-10 questionnaire psychosocial summary score | 48.765 Scores on a scale STANDARD_DEVIATION 8.263 |
| Race/Ethnicity, Customized Not reported | 24 Participants |
| Respiratory Rate | 19.6 Breath per minute STANDARD_DEVIATION 4.4 |
| Right atrial diastolic area | 16.944 Square centimeter (cm^2) STANDARD_DEVIATION 11.071 |
| Right atrial diastolic area index | 12.788 Ratio STANDARD_DEVIATION 6.977 |
| Right atrial systolic area | 12.017 Square centimeter (cm^2) STANDARD_DEVIATION 9.391 |
| Right atrial systolic area index | 8.996 Ratio STANDARD_DEVIATION 6.021 |
| Right ventricular cardiac index | 4.343 Liter/minute/square meter (L/min/m^2) STANDARD_DEVIATION 1.599 |
| Right ventricular cardiac output | 5.511 Liter per minute (L/min) STANDARD_DEVIATION 2.093 |
| Right ventricular diastolic area | 27.155 Square centimeter (cm^2) STANDARD_DEVIATION 11.993 |
| Right ventricular diastolic area index | 20.722 Ratio STANDARD_DEVIATION 6.564 |
| Right ventricular fractional area change | 25.7 Percentage (%) STANDARD_DEVIATION 8.5 |
| Right ventricular systolic area | 20.235 Square centimeter (cm^2) STANDARD_DEVIATION 9.343 |
| Right ventricular systolic area index | 15.613 Ratio STANDARD_DEVIATION 5.745 |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 13 Participants |
| Sodium | 140.5 millimole per Liter (mmol/L) STANDARD_DEVIATION 2 |
| Systolic blood pressure | 112.9 millimetre of mercury (mmHg) STANDARD_DEVIATION 10.9 |
| Systolic pulmonary artery pressure | 117.2 millimetre of mercury (mmHg) STANDARD_DEVIATION 51.6 |
| Tricuspid annular plane systolic excursion | 18.82 Millimeter (mm) STANDARD_DEVIATION 4.21 |
| Tricuspid regurgitation peak velocity | 4.915 Meter/second (m/s) STANDARD_DEVIATION 1.1 |
| Urea | 25.17 microgram per deciliter (mg/dL) STANDARD_DEVIATION 7.23 |
| WHO functional class Class I | 1 Participants |
| WHO functional class Class II | 18 Participants |
| WHO functional class Class III | 5 Participants |
| WHO functional class Class IV | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 15 / 24 |
| serious Total, serious adverse events | 4 / 24 |
Outcome results
Primary
Change in Blood Pressure From Baseline
Mean changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline are reported.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Blood Pressure From Baseline | SBP | -3.1 millimetre of mercury (mmHg) | Standard Deviation 10.5 |
| Riociguat >=6 to <18 Years | Change in Blood Pressure From Baseline | DBP | -2.4 millimetre of mercury (mmHg) | Standard Deviation 10 |
Primary
Change in Clinical Chemistry (Alanine Aminotransferase) From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Clinical Chemistry (Alanine Aminotransferase) From Baseline | -1.01 Units per liter (U/L) | Standard Deviation 9.86 |
Primary
Change in Clinical Chemistry (Aspartate Aminotransferase) From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Clinical Chemistry (Aspartate Aminotransferase) From Baseline | -1.94 Units per liter (U/L) | Standard Deviation 6.52 |
Primary
Change in Clinical Chemistry (Blood Urea Nitrogen) From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Clinical Chemistry (Blood Urea Nitrogen) From Baseline | 1.3 microgram per deciliter (mg/dL) | Standard Deviation 4.3 |
Primary
Change in Clinical Chemistry (eGFR) From Baseline
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
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Clinical Chemistry (eGFR) From Baseline | -4.459 milliliter/minute/1.73 square meter | Standard Deviation 25.686 |
Primary
Change in Clinical Chemistry (Gamma Glutamyl Transferase) From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Clinical Chemistry (Gamma Glutamyl Transferase) From Baseline | 1.7 Units per liter (U/L) | Standard Deviation 4 |
Primary
Change in Clinical Chemistry (Sodium) From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Clinical Chemistry (Sodium) From Baseline | -1.0 millimole per Liter (mmol/L) | Standard Deviation 1.9 |
Primary
Change in Clinical Chemistry (Urea) From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Clinical Chemistry (Urea) From Baseline | 4.06 microgram per deciliter (mg/dL) | Standard Deviation 10.52 |
Primary
Change in Heart Rate From Baseline
Mean change in heart rate from baseline is reported.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Heart Rate From Baseline | 4.1 Beats per minute (BPM) | Standard Deviation 10.1 |
Primary
Change in Hematology Parameter (Neutrophils/Leucocytes Ratio) From Baseline
Hematology parameters were collected. Parameters with a decrease or increase in the mean value compared to baseline are reported in this data set.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Hematology Parameter (Neutrophils/Leucocytes Ratio) From Baseline | 5.71 Percentage of leucocytes in blood | Standard Deviation 11.73 |
Primary
Change in Hematology Parameters (Lymphocytes/Leucocytes Ratio) From Baseline
Hematology parameters were collected. Parameters with a decrease or increase in the mean value compared to baseline are reported in this data set.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Hematology Parameters (Lymphocytes/Leucocytes Ratio) From Baseline | -4.77 Percentage of leucocytes in blood | Standard Deviation 11.08 |
Primary
Change in Hematology Parameters (Platelets) From Baseline
Hematology parameters were collected. Parameters with a decrease or increase in the mean value compared to baseline are reported in this data set.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Hematology Parameters (Platelets) From Baseline | -4.4 Giga platelets per Liter | Standard Deviation 51.1 |
Primary
Change in Respiratory Rate From Baseline
Mean change in respiratory rate from baseline is reported.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Respiratory Rate From Baseline | 0.3 Breath per minute | Standard Deviation 3.3 |
Primary
Number of Participants With Any Treatment-emergent Adverse Events
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).
Time frame: 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)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Number of Participants With Any Treatment-emergent Adverse Events | Any TEAE | 20 Participants |
| Riociguat >=6 to <18 Years | Number of Participants With Any Treatment-emergent Adverse Events | Any serious TEAE | 4 Participants |
Primary
Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age | Transitioned from Delayed to Advanced | 0 Participants |
| Riociguat >=6 to <18 Years | Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age | Transitioned from Delayed to In Accordance | 0 Participants |
| Riociguat >=6 to <18 Years | Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age | Transitioned from In Accordance to Delayed | 1 Participants |
| Riociguat >=6 to <18 Years | Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age | Transitioned from In Accordance to Advanced | 3 Participants |
| Riociguat >=6 to <18 Years | Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age | Transitioned from In Accordance to Missing | 1 Participants |
| Riociguat >=6 to <18 Years | Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age | Transitioned from Advanced to Delayed | 1 Participants |
| Riociguat >=6 to <18 Years | Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age | Transitioned from Advanced to In Accordance | 0 Participants |
Primary
Plasma Concentration of BAY60-4552 at Week 0
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
Time frame: Week 0 (30-90 minutes post-dose; 2.5-4 hours post-dose)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat >=6 to <18 Years | Plasma Concentration of BAY60-4552 at Week 0 | W0 (30-90 min post-dose) | NA microgram per liter (mcg/L) | — |
| Riociguat >=6 to <18 Years | 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
Plasma Concentration of BAY60-4552 at Week 4
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.
Time frame: Week 4 (pre-dose)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Plasma Concentration of BAY60-4552 at Week 4 | 12.700 microgram per liter (mcg/L) | — |
| Riociguat 1.0 mg or Equivalent - PK | Plasma Concentration of BAY60-4552 at Week 4 | 48.822 microgram per liter (mcg/L) | Geometric Coefficient of Variation 193.584 |
| Riociguat 2.0 mg or Equivalent - PK | Plasma Concentration of BAY60-4552 at Week 4 | 38.579 microgram per liter (mcg/L) | Geometric Coefficient of Variation 27.242 |
Primary
Plasma Concentration of BAY60-4552 at Week 8
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.
Time frame: Week 8 (pre-dose)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Plasma Concentration of BAY60-4552 at Week 8 | 23.065 microgram per liter (mcg/L) | Geometric Coefficient of Variation 91.296 |
| Riociguat 1.0 mg or Equivalent - PK | Plasma Concentration of BAY60-4552 at Week 8 | 13.200 microgram per liter (mcg/L) | — |
| Riociguat 2.0 mg or Equivalent - PK | Plasma Concentration of BAY60-4552 at Week 8 | 49.600 microgram per liter (mcg/L) | — |
| Riociguat 2.5 mg or Equivalent - PK | Plasma Concentration of BAY60-4552 at Week 8 | 65.849 microgram per liter (mcg/L) | Geometric Coefficient of Variation 26.864 |
Primary
Plasma Concentration of Riociguat at Week 0
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.
Time frame: Week 0 (30-90 minutes post-dose; 2.5-4 hours post-dose)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat >=6 to <18 Years | 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 |
| Riociguat >=6 to <18 Years | 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 55.69 |
Primary
Plasma Concentration of Riociguat at Week 4
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.
Time frame: Week 4 (pre-dose)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Plasma Concentration of Riociguat at Week 4 | 4.510 microgram per liter (mcg/L) | — |
| Riociguat 1.0 mg or Equivalent - PK | Plasma Concentration of Riociguat at Week 4 | 65.585 microgram per liter (mcg/L) | Geometric Coefficient of Variation 47.727 |
| Riociguat 2.0 mg or Equivalent - PK | Plasma Concentration of Riociguat at Week 4 | 31.126 microgram per liter (mcg/L) | Geometric Coefficient of Variation 89.79 |
Primary
Plasma Concentration of Riociguat at Week 8
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.
Time frame: Week 8 (pre-dose)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Plasma Concentration of Riociguat at Week 8 | 11.650 microgram per liter (mcg/L) | Geometric Coefficient of Variation 244.238 |
| Riociguat 1.0 mg or Equivalent - PK | Plasma Concentration of Riociguat at Week 8 | 27.100 microgram per liter (mcg/L) | — |
| Riociguat 2.0 mg or Equivalent - PK | Plasma Concentration of Riociguat at Week 8 | 14.000 microgram per liter (mcg/L) | — |
| Riociguat 2.5 mg or Equivalent - PK | Plasma Concentration of Riociguat at Week 8 | 32.381 microgram per liter (mcg/L) | Geometric Coefficient of Variation 137.719 |
Secondary
Change in 6-minute Walking Distance From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in 6-minute Walking Distance From Baseline | 23.01 Meter | Standard Deviation 68.8 |
Secondary
Change in BNP From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in BNP From Baseline | 7.45 Picograms per milliliter (pg/mL) | Standard Deviation 10.65 |
Secondary
Change in Estimated Right Atrial Pressure From Baseline
Estimated right atrial pressure was measured by echocardiography.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Estimated Right Atrial Pressure From Baseline | -0.6 millimetre of mercury (mmHg) | Standard Deviation 3.6 |
Secondary
Change in Left Ventricular Eccentricity Index From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Left Ventricular Eccentricity Index From Baseline | 0.002 Ratio | Standard Deviation 0.907 |
Secondary
Change in NT-proBNP From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in NT-proBNP From Baseline | -65.77 picograms per milliliter (pg/mL) | Standard Deviation 585.41 |
Secondary
Change in Pericardial Effusion From Baseline
Pericardial effusion was measured by echocardiography.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Riociguat >=6 to <18 Years | Change in Pericardial Effusion From Baseline | 1.040 Millimeter (mm) |
Secondary
Change in Pulmonary Artery Acceleration Time From Baseline
Pulmonary artery acceleration time was measured by echocardiography.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Pulmonary Artery Acceleration Time From Baseline | -7.777 Millisecond (msec) | Standard Deviation 35.898 |
Secondary
Change in Quality of Life Evaluated by PedsQL Scale
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Quality of Life Evaluated by PedsQL Scale | Total scale score | 3.49 Scores on a scale | Standard Deviation 10.81 |
| Riociguat >=6 to <18 Years | Change in Quality of Life Evaluated by PedsQL Scale | Psychosocial health summary score | 3.07 Scores on a scale | Standard Deviation 11.21 |
| Riociguat >=6 to <18 Years | Change in Quality of Life Evaluated by PedsQL Scale | Physical health summary score | 4.28 Scores on a scale | Standard Deviation 13.51 |
Secondary
Change in Quality of Life Evaluated by SF-10 Questionnaire From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat >=6 to <18 Years | 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 |
| Riociguat >=6 to <18 Years | 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 |
Secondary
Change in Right Atrial Diastolic Area From Baseline
Right atrial diastolic area was measured by echocardiography.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Right Atrial Diastolic Area From Baseline | 1.078 Square centimeter (cm^2) | Standard Deviation 3.33 |
Secondary
Change in Right Atrial Diastolic Area Index From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Right Atrial Diastolic Area Index From Baseline | 0.643 Ratio | Standard Deviation 2.314 |
Secondary
Change in Right Atrial Systolic Area From Baseline
Right atrial systolic area was measured by echocardiography.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Right Atrial Systolic Area From Baseline | 0.424 Square centimeter (cm^2) | Standard Deviation 3.758 |
Secondary
Change in Right Atrial Systolic Area Index From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Right Atrial Systolic Area Index From Baseline | 0.329 Ratio | Standard Deviation 2.417 |
Secondary
Change in Right Ventricular Cardiac Index From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Right Ventricular Cardiac Index From Baseline | 0.188 Liter/minute/square meter (L/min/m^2) | Standard Deviation 2.094 |
Secondary
Change in Right Ventricular Cardiac Output From Baseline
Right ventricular cardiac output was measured by echocardiography.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Right Ventricular Cardiac Output From Baseline | 0.457 Liter per minute (L/min) | Standard Deviation 3.066 |
Secondary
Change in Right Ventricular Diastolic Area From Baseline
Right ventricular diastolic area was measured by echocardiography.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Right Ventricular Diastolic Area From Baseline | 0.618 Square centimeter (cm^2) | Standard Deviation 4.519 |
Secondary
Change in Right Ventricular Diastolic Area Index From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Right Ventricular Diastolic Area Index From Baseline | 0.451 Ratio | Standard Deviation 3.562 |
Secondary
Change in Right Ventricular Fractional Area Change From Baseline
Right ventricular fractional area change was measured by echocardiography.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Right Ventricular Fractional Area Change From Baseline | -4.3 Percentage (%) of area | Standard Deviation 7.3 |
Secondary
Change in Right Ventricular Systolic Area From Baseline
Right ventricular systolic area was measured by echocardiography.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Right Ventricular Systolic Area From Baseline | 1.725 Square centimeter (cm^2) | Standard Deviation 3.847 |
Secondary
Change in Right Ventricular Systolic Area Index From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Right Ventricular Systolic Area Index From Baseline | 1.244 Ratio | Standard Deviation 3.277 |
Secondary
Change in Systolic Pulmonary Artery Pressure From Baseline
Systolic pulmonary artery pressure was measured by echocardiography.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Systolic Pulmonary Artery Pressure From Baseline | 5.7 millimetre of mercury (mmHg) | Standard Deviation 49 |
Secondary
Change in Tricuspid Annular Plane Systolic Excursion From Baseline
Tricuspid annular plane systolic excursion (TAPSE) was measured by echocardiography.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Tricuspid Annular Plane Systolic Excursion From Baseline | -1.27 Millimeter (mm) | Standard Deviation 3.87 |
Secondary
Change in Tricuspid Regurgitation Peak Velocity From Baseline
Tricuspid regurgitation peak velocity was measured by echocardiography.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Change in Tricuspid Regurgitation Peak Velocity From Baseline | -0.085 Meter/second (m/s) | Standard Deviation 0.726 |
Secondary
Number of Subjects With Change in WHO Functional Class From Baseline
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.
Time frame: Baseline and Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Number of Subjects With Change in WHO Functional Class From Baseline | -2 classes | 0 Participants |
| Riociguat >=6 to <18 Years | Number of Subjects With Change in WHO Functional Class From Baseline | -1 classes | 0 Participants |
| Riociguat >=6 to <18 Years | Number of Subjects With Change in WHO Functional Class From Baseline | 0 classes | 21 Participants |
| Riociguat >=6 to <18 Years | Number of Subjects With Change in WHO Functional Class From Baseline | 1 classes | 0 Participants |
| Riociguat >=6 to <18 Years | Number of Subjects With Change in WHO Functional Class From Baseline | 2 classes | 0 Participants |
| Riociguat >=6 to <18 Years | Number of Subjects With Change in WHO Functional Class From Baseline | 3 classes | 0 Participants |
| Riociguat >=6 to <18 Years | Number of Subjects With Change in WHO Functional Class From Baseline | -3 classes | 0 Participants |
Secondary
Number of Subjects With Clinical Worsening
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.
Time frame: Up to Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Riociguat >=6 to <18 Years | Number of Subjects With Clinical Worsening | 2 Participants |
Other Pre-specified
Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 0
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.
Time frame: At the beginning of the treatment (Week 0)
Population: Participants in safety analysis set (SAF) with assessment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 0 | Comfortable | 7 Participants |
| Riociguat >=6 to <18 Years | Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 0 | Indifferent | 8 Participants |
| Riociguat >=6 to <18 Years | Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 0 | Displeased | 0 Participants |
| Riociguat >=6 to <18 Years | Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 0 | Missing | 1 Participants |
Other Pre-specified
Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 24
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.
Time frame: Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with assessment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 24 | Indifferent | 5 Participants |
| Riociguat >=6 to <18 Years | Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 24 | Comfortable | 6 Participants |
| Riociguat >=6 to <18 Years | Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 24 | Displeased | 2 Participants |
| Riociguat >=6 to <18 Years | Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 24 | Missing | 1 Participants |
Other Pre-specified
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0
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.
Time frame: At the beginning of the treatment (Week 0)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Disgusting | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Fruity | Yes | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Sweet | Yes | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Sweet | No | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Sweet | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Sour | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Sour | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Sour | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Bitter | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Bitter | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Bitter | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Salty | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Salty | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Salty | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Disgusting | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Disgusting | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Fruity | No | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 | Fruity | Unsure | 0 Participants |
Other Pre-specified
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24
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.
Time frame: Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Sweet | Unsure | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Sweet | Yes | 2 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Sweet | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Sour | Yes | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Sour | No | 3 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Sour | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Bitter | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Bitter | No | 3 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Bitter | Unsure | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Salty | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Salty | No | 4 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Salty | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Disgusting | Yes | 4 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Disgusting | No | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Disgusting | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Fruity | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Fruity | No | 2 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 | Fruity | Unsure | 2 Participants |
Other Pre-specified
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0
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.
Time frame: At the beginning of the treatment (Week 0)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Like Sand | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Like Sand | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Gooey | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Gooey | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Gooey | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Slimy | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Slimy | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Slimy | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Creamy | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Creamy | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Creamy | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Like Sand | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Sticky | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Sticky | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 | Sticky | Unsure | 0 Participants |
Other Pre-specified
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24
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.
Time frame: Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with assessment
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Like sand | Yes | 3 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Like sand | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Like sand | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Sticky | Yes | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Sticky | No | 3 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Sticky | Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Gooey | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Gooey | No | 3 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Gooey | Unsure | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Slimy | Yes | 2 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Slimy | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Slimy | Unsure | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Creamy | Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Creamy | No | 2 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 | Creamy | Unsure | 2 Participants |
Other Pre-specified
Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 0
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).
Time frame: At the beginning of the treatment (Week 0)
Population: Participants in safety analysis set (SAF) with assessment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 0 | Like the taste after swallowing - Unsure | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 0 | Like the taste after swallowing - Yes | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 0 | Like the taste after swallowing - No | 0 Participants |
Other Pre-specified
Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 24
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).
Time frame: Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with assessment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Riociguat >=6 to <18 Years | Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 24 | Like the taste after swallowing - Yes | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 24 | Like the taste after swallowing - No | 3 Participants |
| Riociguat >=6 to <18 Years | 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
Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0
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).
Time frame: At the beginning of the treatment (Week 0)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Riociguat >=6 to <18 Years | 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 |
| Riociguat >=6 to <18 Years | 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 |
| Riociguat >=6 to <18 Years | 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 |
| Riociguat >=6 to <18 Years | 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 |
| Riociguat >=6 to <18 Years | 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 |
| Riociguat >=6 to <18 Years | 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 |
| Riociguat >=6 to <18 Years | 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 |
| Riociguat >=6 to <18 Years | 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 |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 | Like the drink | Yes | 9 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 | Like the drink | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 | Like the drink | Unsure | 5 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 | Like the drink | Missing | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 | Like to drink again | Yes | 12 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 | Like to drink again | No | 0 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 | Like to drink again | Unsure | 3 Participants |
| Riociguat >=6 to <18 Years | 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
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24
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).
Time frame: Week 24 (plus/minus 5 days)
Population: Participants in safety analysis set (SAF) with evaluable data
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like the drink | Yes | 6 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like the drink | Missing | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like the look of the drink | Yes | 6 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like the look of the drink | No | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like the look of the drink | Unsure | 6 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like the look of the drink | Missing | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like the smell of the drink | Yes | 7 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like the smell of the drink | No | 2 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like the smell of the drink | Unsure | 4 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like the smell of the drink | Missing | 1 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like the drink | No | 4 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like the drink | Unsure | 3 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like to drink again | Yes | 6 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like to drink again | No | 3 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like to drink again | Unsure | 4 Participants |
| Riociguat >=6 to <18 Years | Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 | Like to drink again | Missing | 1 Participants |