PATENT-CHILD: Riociguat in Children With Pulmonary Arterial Hypertension (PAH)

Sponsor

Bayer (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02562235

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Locations

Arm

183

Anticipated Duration (Months)

1.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension, Pulmonary	Drug: Riociguat (Adempas, BAY63-2521)	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Open-label, Individual Dose Titration Study to Evaluate Safety, Tolerability and Pharmacokinetics of Riociguat in Children From 6 to Less Than 18 Years of Age With Pulmonary Arterial Hypertension (PAH)

Actual Study Start Date :

Oct 29, 2015

Actual Primary Completion Date :

Mar 7, 2020

Anticipated Study Completion Date :

Jan 27, 2031

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Riociguat 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.	Drug: Riociguat (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.

Arm

Intervention/Treatment

Experimental: Riociguat

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.

Drug: Riociguat (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.

Outcome Measures

Primary Outcome Measures

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
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.

Secondary Outcome Measures

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.
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 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 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.

Other Outcome Measures

Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0 [At the beginning of the treatment (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).
Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24 [Week 24 (plus/minus 5 days)]
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).
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0 [At the beginning of the treatment (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".
Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24 [Week 24 (plus/minus 5 days)]
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".
Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0 [At the beginning of the treatment (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".
Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24 [Week 24 (plus/minus 5 days)]
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".
Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 0 [At the beginning of the treatment (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).
Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 24 [Week 24 (plus/minus 5 days)]
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).
Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 0 [At the beginning of the treatment (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".
Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 24 [Week 24 (plus/minus 5 days)]
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".

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	IPS Centro Médico Imbanaco de Cali S.A.	Cali	Valle Del Cauca	Colombia
2	Universitätsklinikum Heidelberg	Heidelberg	Baden-Württemberg	Germany	69120
3	Universitätsklinikum Ulm	Ulm	Baden-Württemberg	Germany	89075
4	Deutsches Herzzentrum	Berlin		Germany	13353
5	Gottsegen Gyorgy Orszagos Kardiologiai Intezet	Budapest		Hungary	1096
6	SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont	Szeged		Hungary	6725
7	A.O.U. di Padova	Padova	Veneto	Italy	35128
8	Aichi Children's Health and Medical Center	Obu	Aichi	Japan	474-8710
9	National Cerebral and Cardiovascular Center	Suita	Osaka	Japan	564-8565
10	Osaka University Hospital	Suita	Osaka	Japan	565-0871
11	Keio University Hospital	Shinjuku-ku	Tokyo	Japan	160-8582
12	Operadora de Hospitales Angeles S. A. de C. V.	Huixquilucan		Mexico	52763
13	Instituto Nacional de Cardiología "Ignacio Chávez"	Mexico D.F.		Mexico	14080
14	Wojewodzki Szpital Specjalistyczny - Wroclaw	Wroclaw		Poland	51-124
15	Veterans General Hospital	Kaoshiung		Taiwan	81346
16	Hacettepe Universitesi Tip Fakultesi	Ankara		Turkey	06100

Sponsors and Collaborators

Bayer
Merck Sharp & Dohme LLC

Investigators

Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.

Responsible Party:

Bayer

ClinicalTrials.gov Identifier:

NCT02562235

Other Study ID Numbers:

15681
2014-003952-29

First Posted:

Sep 29, 2015

Last Update Posted:

Aug 17, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Bayer

Pulmonary arterial hypertension

Additional relevant MeSH terms:

Pulmonary Arterial Hypertension

Hypertension, Pulmonary

Hypertension

Riociguat

Study Results

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Period Title: Overall Study
STARTED	24
COMPLETED	21
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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 Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.8 (2.8)
Sex: Female, Male (Count of Participants)
Female	11 45.8%
Male	13 54.2%
Race/Ethnicity, Customized (Count of Participants)
Not reported	24 100%
Bone age compared to chronological age (Count of Participants)
Delayed	1 4.2%
In accordance	12 50%
Advanced	10 41.7%
Missing	1 4.2%
WHO functional class (Count of Participants)
Class I	1 4.2%
Class II	18 75%
Class III	5 20.8%
Class IV	0 0%
Heart rate (Beats per minute (BPM)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Beats per minute (BPM)]	84.5 (19.0)
Diastolic blood pressure (millimetre of mercury (mmHg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimetre of mercury (mmHg)]	63.8 (7.9)
Systolic blood pressure (millimetre of mercury (mmHg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimetre of mercury (mmHg)]	112.9 (10.9)
Respiratory Rate (Breath per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Breath per minute]	19.6 (4.4)
6-minute walking distance (Meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Meter]	442.12 (109.67)
N-terminal prohormone brain-type natriuretic peptide (Picograms per milliliter (pg/mL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Picograms per milliliter (pg/mL)]	982.68 (1595.77)
Brain-type natriuretic peptide (Picograms per milliliter (pg/mL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Picograms per milliliter (pg/mL)]	10.46 (9.10)
Quality of life evaluated by SF-10 questionnaire physical summary score (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	30.964 (13.335)
Quality of life evaluated by SF-10 questionnaire psychosocial summary score (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	48.765 (8.263)
Quality of life evaluated by PedsQL total scale score (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	69.77 (16.29)
Quality of life evaluated by PedsQL physical health summary score (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	64.43 (15.80)
Quality of life evaluated by PedsQL psychosocial health summary score (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	72.62 (19.20)
Estimate right atrial pressure (millimetre of mercury (mmHg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimetre of mercury (mmHg)]	9.2 (2.9)
Left ventricular eccentricity index (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	2.099 (1.275)
Pulmonary artery acceleration time (Millisecond (msec)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millisecond (msec)]	91.568 (36.853)
Right ventricular cardiac index (Liter/minute/square meter (L/min/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Liter/minute/square meter (L/min/m^2)]	4.343 (1.599)
Right ventricular cardiac output (Liter per minute (L/min)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Liter per minute (L/min)]	5.511 (2.093)
Right atrial diastolic area (Square centimeter (cm^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Square centimeter (cm^2)]	16.944 (11.071)
Right atrial diastolic area index (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	12.788 (6.977)
Right atrial systolic area (Square centimeter (cm^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Square centimeter (cm^2)]	12.017 (9.391)
Right atrial systolic area index (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	8.996 (6.021)
Right ventricular fractional area change (Percentage (%)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage (%)]	25.7 (8.5)
Right ventricular diastolic area (Square centimeter (cm^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Square centimeter (cm^2)]	27.155 (11.993)
Right ventricular diastolic area index (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	20.722 (6.564)
Right ventricular systolic area (Square centimeter (cm^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Square centimeter (cm^2)]	20.235 (9.343)
Right ventricular systolic area index (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	15.613 (5.745)
Systolic pulmonary artery pressure (millimetre of mercury (mmHg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimetre of mercury (mmHg)]	117.2 (51.6)
Tricuspid annular plane systolic excursion (Millimeter (mm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millimeter (mm)]	18.82 (4.21)
Tricuspid regurgitation peak velocity (Meter/second (m/s)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Meter/second (m/s)]	4.915 (1.100)
Pericardial effusion (Millimeter (mm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millimeter (mm)]	1.280 (0.212)
Platelets (Giga platelets per liter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Giga platelets per liter]	218.8 (50.6)
Lymphocytes/leucocytes ratio (Percentage of leucocytes in blood) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of leucocytes in blood]	48.98 (8.15)
Neutrophils/leucocytes ratio (Percentage of leucocytes in blood) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of leucocytes in blood]	18.71 (10.37)
Alanine aminotransferase (Units per liter (U/L)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units per liter (U/L)]	18.71 (10.37)
Aspartate aminotransferase (Units per liter (U/L)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units per liter (U/L)]	23.76 (8.38)
Urea (microgram per deciliter (mg/dL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [microgram per deciliter (mg/dL)]	25.17 (7.23)
Gamma glutamyl transferase (Units per liter (U/L)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units per liter (U/L)]	16.9 (14.5)
Blood urea nitrogen (microgram per deciliter (mg/dL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [microgram per deciliter (mg/dL)]	11.8 (4.7)
Estimated Glomerular Filtration Rate (eGFR) (milliliter/minute/1.73 square meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliliter/minute/1.73 square meter]	117.877 (30.649)
Sodium (millimole per Liter (mmol/L)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimole per Liter (mmol/L)]	140.5 (2.0)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Treatment-emergent Adverse Events
Description	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.

Outcome Measure Data

Analysis Population Description
Safety analysis set (SAF)

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	24
Any TEAE	20 83.3%
Any serious TEAE	4 16.7%

2. Primary Outcome

Title	Change in Heart Rate From Baseline
Description	Mean change in heart rate from baseline is reported.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	21
Mean (Standard Deviation) [Beats per minute (BPM)]	4.1 (10.1)

3. Primary Outcome

Title	Change in Blood Pressure From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	21
SBP	-3.1 (10.5)
DBP	-2.4 (10.0)

4. Primary Outcome

Title	Change in Respiratory Rate From Baseline
Description	Mean change in respiratory rate from baseline is reported.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	18
Mean (Standard Deviation) [Breath per minute]	0.3 (3.3)

5. Primary Outcome

Title	Number of Subjects With Transitions From Baseline in Bone Age Compared to Chronological Age
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	21
Transitioned from Delayed to In Accordance	0 0%
Transitioned from Delayed to Advanced	0 0%
Transitioned from In Accordance to Delayed	1 4.2%
Transitioned from In Accordance to Advanced	3 12.5%
Transitioned from In Accordance to Missing	1 4.2%
Transitioned from Advanced to Delayed	1 4.2%
Transitioned from Advanced to In Accordance	0 0%

6. Primary Outcome

Title	Change in Hematology Parameters (Platelets) From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	20
Mean (Standard Deviation) [Giga platelets per Liter]	-4.4 (51.1)

7. Primary Outcome

Title	Change in Hematology Parameters (Lymphocytes/Leucocytes Ratio) From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	20
Mean (Standard Deviation) [Percentage of leucocytes in blood]	-4.77 (11.08)

8. Primary Outcome

Title	Change in Hematology Parameter (Neutrophils/Leucocytes Ratio) From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	20
Mean (Standard Deviation) [Percentage of leucocytes in blood]	5.71 (11.73)

9. Primary Outcome

Title	Change in Clinical Chemistry (Alanine Aminotransferase) From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	21
Mean (Standard Deviation) [Units per liter (U/L)]	-1.01 (9.86)

10. Primary Outcome

Title	Change in Clinical Chemistry (Aspartate Aminotransferase) From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	21
Mean (Standard Deviation) [Units per liter (U/L)]	-1.94 (6.52)

11. Primary Outcome

Title	Change in Clinical Chemistry (Sodium) From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	19
Mean (Standard Deviation) [millimole per Liter (mmol/L)]	-1.0 (1.9)

12. Primary Outcome

Title	Change in Clinical Chemistry (Blood Urea Nitrogen) From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	14
Mean (Standard Deviation) [microgram per deciliter (mg/dL)]	1.3 (4.3)

13. Primary Outcome

Title	Change in Clinical Chemistry (eGFR) From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	21
Mean (Standard Deviation) [milliliter/minute/1.73 square meter]	-4.459 (25.686)

14. Primary Outcome

Title	Change in Clinical Chemistry (Urea) From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	9
Mean (Standard Deviation) [microgram per deciliter (mg/dL)]	4.06 (10.52)

15. Primary Outcome

Title	Change in Clinical Chemistry (Gamma Glutamyl Transferase) From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	18
Mean (Standard Deviation) [Units per liter (U/L)]	1.7 (4.0)

16. Primary Outcome

Title	Plasma Concentration of Riociguat at Week 0
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat 1.0 mg or Equivalent - PK
Arm/Group Description	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
Measure Participants	22
W0 (30-90 min post-dose)	15.340 (90.536)
W0 (2.5-4 h post-dose)	17.791 (55.690)

17. Primary Outcome

Title	Plasma Concentration of Riociguat at Week 4
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat 0.5 mg or Equivalent - PK	Riociguat 1.0 mg or Equivalent - PK	Riociguat 2.0 mg or Equivalent - PK
Arm/Group Description	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	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	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
Measure Participants	1	2	17
Geometric Mean (Geometric Coefficient of Variation) [microgram per liter (mcg/L)]	4.510 (NA)	65.585 (47.727)	31.126 (89.790)

18. Primary Outcome

Title	Plasma Concentration of Riociguat at Week 8
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat 0.5 mg or Equivalent - PK	Riociguat 1.0 mg or Equivalent - PK	Riociguat 2.0 mg or Equivalent - PK	Riociguat 2.5 mg or Equivalent - PK
Arm/Group Description	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	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	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	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
Measure Participants	2	1	1	15
Geometric Mean (Geometric Coefficient of Variation) [microgram per liter (mcg/L)]	11.650 (244.238)	27.100 (NA)	14.000 (NA)	32.381 (137.719)

19. Primary Outcome

Title	Plasma Concentration of BAY60-4552 at Week 0
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat 1.0 mg or Equivalent - PK
Arm/Group Description	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
Measure Participants	22
W0 (30-90 min post-dose)	NA (NA)
W0 (2.5-4 h post-dose)	3.922 (94.399)

20. Primary Outcome

Title	Plasma Concentration of BAY60-4552 at Week 4
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat 0.5 mg or Equivalent - PK	Riociguat 1.0 mg or Equivalent - PK	Riociguat 2.0 mg or Equivalent - PK
Arm/Group Description	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	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	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
Measure Participants	1	2	17
Geometric Mean (Geometric Coefficient of Variation) [microgram per liter (mcg/L)]	12.700 (NA)	48.822 (193.584)	38.579 (27.242)

21. Primary Outcome

Title	Plasma Concentration of BAY60-4552 at Week 8
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat 0.5 mg or Equivalent - PK	Riociguat 1.0 mg or Equivalent - PK	Riociguat 2.0 mg or Equivalent - PK	Riociguat 2.5 mg or Equivalent - PK
Arm/Group Description	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	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	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	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
Measure Participants	2	1	1	15
Geometric Mean (Geometric Coefficient of Variation) [microgram per liter (mcg/L)]	23.065 (91.296)	13.200 (NA)	49.600 (NA)	65.849 (26.864)

22. Secondary Outcome

Title	Change in 6-minute Walking Distance From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	19
Mean (Standard Deviation) [Meter]	23.01 (68.80)

23. Secondary Outcome

Title	Number of Subjects With Change in WHO Functional Class From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	21
-3 classes	0 0%
-2 classes	0 0%
-1 classes	0 0%
0 classes	21 87.5%
1 classes	0 0%
2 classes	0 0%
3 classes	0 0%

24. Secondary Outcome

Title	Change in NT-proBNP From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	14
Mean (Standard Deviation) [picograms per milliliter (pg/mL)]	-65.77 (585.41)

25. Secondary Outcome

Title	Change in BNP From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	6
Mean (Standard Deviation) [Picograms per milliliter (pg/mL)]	7.45 (10.65)

26. Secondary Outcome

Title	Change in Quality of Life Evaluated by SF-10 Questionnaire From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	21
Physical summary score	5.79 (12.46)
Psychosocial summary score	1.10 (6.85)

27. Secondary Outcome

Title	Change in Quality of Life Evaluated by PedsQL Scale
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	19
Total scale score	3.49 (10.81)
Physical health summary score	4.28 (13.51)
Psychosocial health summary score	3.07 (11.21)

28. Secondary Outcome

Title	Number of Subjects With Clinical Worsening
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	24
Count of Participants [Participants]	2 8.3%

29. Secondary Outcome

Title	Change in Estimated Right Atrial Pressure From Baseline
Description	Estimated right atrial pressure was measured by echocardiography.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	16
Mean (Standard Deviation) [millimetre of mercury (mmHg)]	-0.6 (3.6)

30. Secondary Outcome

Title	Change in Left Ventricular Eccentricity Index From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	15
Mean (Standard Deviation) [Ratio]	0.002 (0.907)

31. Secondary Outcome

Title	Change in Pericardial Effusion From Baseline
Description	Pericardial effusion was measured by echocardiography.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	1
Mean (Standard Deviation) [Millimeter (mm)]	1.040 (NA)

32. Secondary Outcome

Title	Change in Pulmonary Artery Acceleration Time From Baseline
Description	Pulmonary artery acceleration time was measured by echocardiography.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	15
Mean (Standard Deviation) [Millisecond (msec)]	-7.777 (35.898)

33. Secondary Outcome

Title	Change in Right Ventricular Cardiac Index From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	13
Mean (Standard Deviation) [Liter/minute/square meter (L/min/m^2)]	0.188 (2.094)

34. Secondary Outcome

Title	Change in Right Ventricular Cardiac Output From Baseline
Description	Right ventricular cardiac output was measured by echocardiography.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	13
Mean (Standard Deviation) [Liter per minute (L/min)]	0.457 (3.066)

35. Secondary Outcome

Title	Change in Right Atrial Diastolic Area From Baseline
Description	Right atrial diastolic area was measured by echocardiography.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	16
Mean (Standard Deviation) [Square centimeter (cm^2)]	1.078 (3.330)

36. Secondary Outcome

Title	Change in Right Atrial Diastolic Area Index From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	16
Mean (Standard Deviation) [Ratio]	0.643 (2.314)

37. Secondary Outcome

Title	Change in Right Atrial Systolic Area From Baseline
Description	Right atrial systolic area was measured by echocardiography.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	16
Mean (Standard Deviation) [Square centimeter (cm^2)]	0.424 (3.758)

38. Secondary Outcome

Title	Change in Right Atrial Systolic Area Index From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	16
Mean (Standard Deviation) [Ratio]	0.329 (2.417)

39. Secondary Outcome

Title	Change in Right Ventricular Fractional Area Change From Baseline
Description	Right ventricular fractional area change was measured by echocardiography.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	15
Mean (Standard Deviation) [Percentage (%) of area]	-4.3 (7.3)

40. Secondary Outcome

Title	Change in Right Ventricular Diastolic Area From Baseline
Description	Right ventricular diastolic area was measured by echocardiography.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	15
Mean (Standard Deviation) [Square centimeter (cm^2)]	0.618 (4.519)

41. Secondary Outcome

Title	Change in Right Ventricular Diastolic Area Index From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	15
Mean (Standard Deviation) [Ratio]	0.451 (3.562)

42. Secondary Outcome

Title	Change in Right Ventricular Systolic Area From Baseline
Description	Right ventricular systolic area was measured by echocardiography.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	15
Mean (Standard Deviation) [Square centimeter (cm^2)]	1.725 (3.847)

43. Secondary Outcome

Title	Change in Right Ventricular Systolic Area Index From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	15
Mean (Standard Deviation) [Ratio]	1.244 (3.277)

44. Secondary Outcome

Title	Change in Systolic Pulmonary Artery Pressure From Baseline
Description	Systolic pulmonary artery pressure was measured by echocardiography.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	3
Mean (Standard Deviation) [millimetre of mercury (mmHg)]	5.7 (49.0)

45. Secondary Outcome

Title	Change in Tricuspid Annular Plane Systolic Excursion From Baseline
Description	Tricuspid annular plane systolic excursion (TAPSE) was measured by echocardiography.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	15
Mean (Standard Deviation) [Millimeter (mm)]	-1.27 (3.87)

46. Secondary Outcome

Title	Change in Tricuspid Regurgitation Peak Velocity From Baseline
Description	Tricuspid regurgitation peak velocity was measured by echocardiography.
Time Frame	Baseline and Week 24 (plus/minus 5 days)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	10
Mean (Standard Deviation) [Meter/second (m/s)]	-0.085 (0.726)

47. Other Pre-specified Outcome

Title	Taste and Texture (Questions 1 to 4) of the Oral Suspension of Riociguat at Week 0
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	16
Yes	4 16.7%
No	2 8.3%
Unsure	9 37.5%
Missing	1 4.2%
Yes	4 16.7%
No	2 8.3%
Unsure	9 37.5%
Missing	1 4.2%
Yes	9 37.5%
No	1 4.2%
Unsure	5 20.8%
Missing	1 4.2%
Yes	12 50%
No	0 0%
Unsure	3 12.5%
Missing	1 4.2%

48. Other Pre-specified Outcome

Title	Taste and Texture (Questions 1 to 4) the Oral Suspension of Riociguat at Week 24
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	14
Yes	6 25%
No	1 4.2%
Unsure	6 25%
Missing	1 4.2%
Yes	7 29.2%
No	2 8.3%
Unsure	4 16.7%
Missing	1 4.2%
Yes	6 25%
No	4 16.7%
Unsure	3 12.5%
Missing	1 4.2%
Yes	6 25%
No	3 12.5%
Unsure	4 16.7%
Missing	1 4.2%

49. Other Pre-specified Outcome

Title	Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 0
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	1
Yes	1 4.2%
No	0 0%
Unsure	0 0%
Yes	0 0%
No	1 4.2%
Unsure	0 0%
Yes	0 0%
No	1 4.2%
Unsure	0 0%
Yes	0 0%
No	1 4.2%
Unsure	0 0%
Yes	0 0%
No	1 4.2%
Unsure	0 0%
Yes	1 4.2%
No	0 0%
Unsure	0 0%

50. Other Pre-specified Outcome

Title	Taste and Texture (Question 5) of the Oral Suspension of Riociguat at Week 24
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	4
Yes	2 8.3%
No	1 4.2%
Unsure	1 4.2%
Yes	1 4.2%
No	3 12.5%
Unsure	0 0%
Yes	0 0%
No	3 12.5%
Unsure	1 4.2%
Yes	0 0%
No	4 16.7%
Unsure	0 0%
Yes	4 16.7%
No	0 0%
Unsure	0 0%
Yes	0 0%
No	2 8.3%
Unsure	2 8.3%

51. Other Pre-specified Outcome

Title	Taste and Texture (Question 6) of the Oral Suspension of Riociguat at Week 0
Description	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)

Outcome Measure Data

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

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	1
Yes	0 0%
No	1 4.2%
Unsure	0 0%
Yes	0 0%
No	1 4.2%
Unsure	0 0%
Yes	0 0%
No	1 4.2%
Unsure	0 0%
Yes	0 0%
No	1 4.2%
Unsure	0 0%
Yes	0 0%
No	1 4.2%
Unsure	0 0%

52. Other Pre-specified Outcome

Title	Taste and Texture (Question 6) of the Oral Suspension of Riociguat in Mouth at Week 24
Description	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)

Outcome Measure Data

Analysis Population Description
Participants in safety analysis set (SAF) with assessment

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	4
Yes	3 12.5%
No	1 4.2%
Unsure	0 0%
Yes	1 4.2%
No	3 12.5%
Unsure	0 0%
Yes	0 0%
No	3 12.5%
Unsure	1 4.2%
Yes	2 8.3%
No	1 4.2%
Unsure	1 4.2%
Yes	0 0%
No	2 8.3%
Unsure	2 8.3%

53. Other Pre-specified Outcome

Title	Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 0
Description	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)

Outcome Measure Data

Analysis Population Description
Participants in safety analysis set (SAF) with assessment

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	1
Like the taste after swallowing - Yes	1 4.2%
Like the taste after swallowing - No	0 0%
Like the taste after swallowing - Unsure	0 0%

54. Other Pre-specified Outcome

Title	Taste and Texture (Question 7) of the Oral Suspension of Riociguat in Mouth at Week 24
Description	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)

Outcome Measure Data

Analysis Population Description
Participants in safety analysis set (SAF) with assessment

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	4
Like the taste after swallowing - Yes	0 0%
Like the taste after swallowing - No	3 12.5%
Like the taste after swallowing - Unsure	1 4.2%

55. Other Pre-specified Outcome

Title	Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 0
Description	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)

Outcome Measure Data

Analysis Population Description
Participants in safety analysis set (SAF) with assessment

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	16
Comfortable	7 29.2%
Indifferent	8 33.3%
Displeased	0 0%
Missing	1 4.2%

56. Other Pre-specified Outcome

Title	Expression Assessment on the Taste and Texture of Oral Suspension of Riociguat - Week 24
Description	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)

Outcome Measure Data

Analysis Population Description
Participants in safety analysis set (SAF) with assessment

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
Measure Participants	14
Comfortable	6 25%
Indifferent	5 20.8%
Displeased	2 8.3%
Missing	1 4.2%

Adverse Events

	Riociguat >=6 to <18 Years
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.
Adverse Event Reporting Description

Arm/Group Title	Riociguat >=6 to <18 Years
Arm/Group Description	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.
All Cause Mortality
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Serious Adverse Events
	Riociguat >=6 to <18 Years
	Affected / at Risk (%)	# Events
Total	4/24 (16.7%)
Cardiac disorders
Right ventricular failure	2/24 (8.3%)	2
Infections and infestations
Vascular device infection	1/24 (4.2%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/24 (4.2%)	2
Skin and subcutaneous tissue disorders
Pain of skin	1/24 (4.2%)	1
Skin swelling	1/24 (4.2%)	1
Vascular disorders
Hypotension	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	Riociguat >=6 to <18 Years
	Affected / at Risk (%)	# Events
Total	15/24 (62.5%)
Gastrointestinal disorders
Abdominal pain	4/24 (16.7%)	5
General disorders
Pyrexia	3/24 (12.5%)	3
Infections and infestations
Gastroenteritis	2/24 (8.3%)	2
Nasopharyngitis	4/24 (16.7%)	7
Upper respiratory tract infection	4/24 (16.7%)	4
Nervous system disorders
Dizziness	2/24 (8.3%)	2
Headache	7/24 (29.2%)	11
Vascular disorders
Hypotension	2/24 (8.3%)	4

Limitations/Caveats

The results should be interpreted with caution due to the limited number of subjects. The number of subjects with clinical worsening events was too low to produce valid Kaplan-Meier estimates for the time to clinical worsening.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title	Therapeutic Area Head
Organization	Bayer
Phone	1-888-8422937
Email	clinical-trials-contact@bayer.com

Responsible Party:

Bayer

ClinicalTrials.gov Identifier:

NCT02562235

Other Study ID Numbers:

15681
2014-003952-29

First Posted:

Sep 29, 2015

Last Update Posted:

Aug 17, 2022

Last Verified:

Aug 1, 2022