do_not_disturb_altRecruitment Complete
Hypertension, pulmonary
Bayer Identifier:
15681
ClinicalTrials.gov Identifier:
EudraCT Number:
EU CT Number:
Not Available
Riociguat in children with pulmonary arterial hypertension (PAH)
Trial purpose
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.
Key Participants Requirements
Sex
BothAge
6 - 17 YearsTrial summary
Enrollment Goal
24Trial Dates
October 2015 - July 2026Phase
Phase 3Could I Receive a placebo
NoProducts
Adempas (Riociguat, BAY63-2521)Accepts Healthy Volunteer
NoWhere to participate
Status | Institution | Location |
---|---|---|
Completed | Wojewodzki Szpital Specjalistyczny - Wroclaw | Wroclaw, 51-124, Poland |
Withdrawn | Instytut "Pomnik – Centrum Zdrowia Dziecka" | Warszawa, 04-730, Poland |
Withdrawn | Ospedale Pediatrico Bambino Gesù | Roma, 165, Italy |
Active, not recruiting | Azienda Ospedale-Università di Padova - UOC Cardiologia Pediatrica | Padova, 35128, Italy |
Withdrawn | Universitair Medisch Centrum Groningen | GRONINGEN, 9713 GZ, Netherlands |
Withdrawn | Great Ormond Street Hospital for Children | London, WC1N 3JH, United Kingdom |
Completed | Hacettepe Universitesi Tip Fakultesi | Ankara, 6100, Turkey |
Withdrawn | Izmir Dr. Behcet Uz Cocuk Hastaliklari Hast | Izmir, 35210, Turkey |
Completed | Deutsches Herzzentrum der Charité (DHZC) | Berlin, 13353, Germany |
Completed | Gottsegen Gyorgy Orszagos Kardiovaszkularis Intezet | Budapest, 1096, Hungary |
Withdrawn | Hopital Necker les enfants malades - Paris | PARIS, 75015, France |
Withdrawn | Eberhard-Karls-Universität Tübingen | Tübingen, 72076, Germany |
Completed | Universitätsklinikum Heidelberg | Heidelberg, 69115, Germany |
Withdrawn | Herz- und Diabeteszentrum Nordrhein-Westfalen (HDZ NRW) | Bad Oeynhausen, 32545, Germany |
Completed | SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont | Szeged, 6720, Hungary |
Withdrawn | Baskent Universitesi Tip Fakultesi Hastanesi | Ankara, 6490, Turkey |
Withdrawn | Hôpital des Enfants | TOULOUSE Cedex 9, 31059, France |
Withdrawn | Hopital du Haut Leveque | Pessac, 33604, France |
Completed | Universitätsklinikum Ulm | Ulm, 89075, Germany |
Withdrawn | Hospital Teresa Herrera | A Coruña, 15006, Spain |
Completed | Keio University Hospital | Shinjuku-ku, 160-8582, Japan |
Completed | Aichi Children's Health and Medical Center | Obu, 474-8710, Japan |
Completed | The University of Osaka Hospital | Suita, 565-0871, Japan |
Completed | National Cerebral and Cardiovascular Center | Suita, 565-8565, Japan |
Withdrawn | Hôpital Erasme/Erasmus Ziekenhuis | Brussels, 1070, Belgium |
Withdrawn | UZ Leuven Gasthuisberg | LEUVEN, 3000, Belgium |
Withdrawn | UZ Gent | GENT, 9000, Belgium |
Withdrawn | Toho University Omori Medical Center | Ota-ku, 143-8541, Japan |
Withdrawn | Kitasato University Hospital | Sagamihara, 252-0375, Japan |
Withdrawn | Emergency Institute of Cardiovascular Diseases & Transplant | Targu Mures, 540136, Romania |
Withdrawn | Niculae Stancioiu Heart Institute Cluj-Napoca | Cluj Napoca, 400001, Romania |
Completed | Clínica Imbanaco S.A.S | Cali, 760042, Colombia |
Withdrawn | Fundación Valle de Lili | Cali, 760032, Colombia |
Withdrawn | La Fe University and Polytechnic Hospital | Nephrology Department | Valencia, 46026, Spain |
Completed | Instituto Nacional de Cardiología "Ignacio Chávez" | México D.F., 14080, Mexico |
Withdrawn | Boston Children's Hospital | Boston, 2115, United States |
Withdrawn | The Children's Hospital | Aurora, 80045, United States |
Withdrawn | Vanderbilt University Medical School | Nashville, 37212-1610, United States |
Withdrawn | Nationwide Children's Hospital | Columbus, 43205-2696, United States |
Withdrawn | East Carolina University | Nephrology & Hypertension | Greenville, 27834, United States |
Withdrawn | National Cheng Kung University Hospital | Tainan, 704, Taiwan |
Completed | Veterans General Hospital | Kaohsiung City, 813414, Taiwan |
Active, not recruiting | Operadora de Hospitales Angeles S. A. de C. V. | Huixquilucan, 52763, Mexico |
Withdrawn | Fundacion Santa Fe Bogota | Cundinamarca, TBC, Colombia |
Withdrawn | Irmandade da Santa Casa de Misericordia de Porto Alegre | Hospital Sao Francisco - Centro Medico Pesquisa Clinica Cardiologia | Porto Alegre, 90020-090, Brazil |
Primary Outcome
- Number of participants with any treatment-emergent adverse eventsAn 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).date_rangeTime 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.
- Change in heart rate from baselineMean change in heart rate from baseline is reported.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in blood pressure from baselineMean changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline are reported.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in respiratory rate from baselineMean change in respiratory rate from baseline is reported.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Number of subjects with transitions from baseline in bone age compared to chronological ageX-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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in hematology parameters (platelets) from baselineHematology parameters were collected. Parameters with a decrease or increase in the mean value compared to baseline are reported in this data set.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in hematology parameters (lymphocytes/leucocytes ratio) from baselineHematology parameters were collected. Parameters with a decrease or increase in the mean value compared to baseline are reported in this data set.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in hematology parameter (neutrophils/leucocytes ratio) from baselineHematology parameters were collected. Parameters with a decrease or increase in the mean value compared to baseline are reported in this data set.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in clinical chemistry (alanine aminotransferase) from baselineClinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in clinical chemistry (aspartate aminotransferase) from baselineClinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in clinical chemistry (sodium) from baselineClinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in clinical chemistry (blood urea nitrogen) from baselineClinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in clinical chemistry (eGFR) from baselineClinical 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 ratedate_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in clinical chemistry (urea) from baselineClinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in clinical chemistry (gamma glutamyl transferase) from baselineClinical chemistry parameters were collected and analyzed. Parameters with a trend to lower or higher mean values from baseline are reported in this data set.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Plasma concentration of riociguat at Week 0For 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.date_rangeTime Frame:Week 0 (30-90 minutes post-dose; 2.5-4 hours post-dose)
- Plasma concentration of riociguat at Week 4For 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.date_rangeTime Frame:Week 4 (pre-dose)
- Plasma concentration of riociguat at Week 8For 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.date_rangeTime Frame:Week 8 (pre-dose)
- Plasma concentration of BAY60-4552 at Week 0BAY60-4552 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 = Weekdate_rangeTime Frame:Week 0 (30-90 minutes post-dose; 2.5-4 hours post-dose)
- Plasma concentration of BAY60-4552 at Week 4BAY60-4552 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.date_rangeTime Frame:Week 4 (pre-dose)
- Plasma concentration of BAY60-4552 at Week 8BAY60-4552 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.date_rangeTime Frame:Week 8 (pre-dose)
Secondary Outcome
- Change in 6-minute walking distance from baseline6-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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Number of subjects with change in WHO functional class from baselineThe 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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in NT-proBNP from baselineLaboratory 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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in BNP from baselineLaboratory 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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in quality of life evaluated by SF-10 questionnaire from baselineSF-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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in quality of life evaluated by PedsQL scaleThe 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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Number of subjects with clinical worseningClinical 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.date_rangeTime Frame:Up to Week 24 (plus/minus 5 days)
- Change in estimated right atrial pressure from baselineEstimated right atrial pressure was measured by echocardiography.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in left ventricular eccentricity index from baselineLeft 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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in pericardial effusion from baselinePericardial effusion was measured by echocardiography.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in pulmonary artery acceleration time from baselinePulmonary artery acceleration time was measured by echocardiography.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in right ventricular cardiac index from baselineRight 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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in right ventricular cardiac output from baselineRight ventricular cardiac output was measured by echocardiography.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in right atrial diastolic area from baselineRight atrial diastolic area was measured by echocardiography.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in right atrial diastolic area index from baselineRight 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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in right atrial systolic area from baselineRight atrial systolic area was measured by echocardiography.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in right atrial systolic area index from baselineRight 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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in right ventricular fractional area change from baselineRight ventricular fractional area change was measured by echocardiography.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in right ventricular diastolic area from baselineRight ventricular diastolic area was measured by echocardiography.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in right ventricular diastolic area index from baselineRight 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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in right ventricular systolic area from baselineRight ventricular systolic area was measured by echocardiography.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in right ventricular systolic area index from baselineRight 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.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in systolic pulmonary artery pressure from baselineSystolic pulmonary artery pressure was measured by echocardiography.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in tricuspid annular plane systolic excursion from baselineTricuspid annular plane systolic excursion (TAPSE) was measured by echocardiography.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
- Change in tricuspid regurgitation peak velocity from baselineTricuspid regurgitation peak velocity was measured by echocardiography.date_rangeTime Frame:Baseline and Week 24 (plus/minus 5 days)
Trial design
Trial Type
InterventionalIntervention Type
DrugTrial Purpose
TreatmentAllocation
N/ABlinding
Open LabelAssignment
Single Group AssignmentTrial Arms
1