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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-018863-40 | EudraCT Number |
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Pulmonary Arterial Hypertension (PAH) is a severe progressive disease with a high mortality. Although several drugs are available for the treatment of PAH none offer a cure, therefore there is still a high medical need for new treatments.
Soluble guanylate cyclase (sGC) is one of the chemicals involved in the pathways controlling vascular tone, which is impaired in patients with PAH. This causes constriction and thickening of the blood vessels wall in the lungs and increase of blood pressure in the lungs. This can lead to the very debilitating symptoms of PAH such as tiredness, shortness of breath on exertion, collapse and often the inability of the patient to perform their daily life activities.
Inhalation of Nitric Oxide, which activates sGC is used to treat PAH, but its effect wears off as soon as inhalation stops. Direct stimulation of sGC using this new compound Riociguat may be a new approach for the treatment of PAH.
The phosphodiesterase 5 (PDE5)-inhibitor Sildenafil is one of licensed treatments for PAH. The Patent Plus is a double-blind, placebo-controlled safety study, designed to investigate the effect of Riociguat on blood pressure in patients with PAH when given in combination with Sildenafil.
Main objective: Evaluation of the pharmacodynamic effect of the combination of Sildenafil and Riociguat on blood pressure and other safety parameters in patients with symptomatic PAH Secondary objectives:To investigate the safety of the riociguat/sildenafil combination and changes in 6-minute walk test, World Health Organization (WHO) functional class, N terminal pro-brain natriuretic peptide, and variables obtained during right-heart catheterization after 12 weeks of treatment; pharmacokinetics of riociguat and sildenafil.
The study consists of one part. In study Part 1 only subjects (18) on stable sildenafil treatment of 20 mg tid have been enrolled. Study Part 2 will not start.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Experimental | Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks. Participants continued to take daily stable sildenafil background treatment according to their prescriptions. |
|
| Placebo | Placebo Comparator | Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks. Participants continued to take daily stable sildenafil background treatment according to their prescriptions. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) | Drug | BAY63-2521: 1 mg tid - 2,5 mg tid oral for 12 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Change From Baseline in Supine Systolic Blood Pressure (SBP) Within 4 Hours Post-dose at Visit 6 (Week 12) | Systolic blood pressure (SBP) was measured as standard vital sign parameter. Range allowed in this study: <= 180 mmHg. In addition, SBP must be >=95 mmHg in the first 2 hours after intake of background treatment with sildenafil. The maximum change from baseline at each visit was defined as the within-subject maximum decrease from baseline (or zero if baseline was lower than all subsequent SBP measurements in that profile) within 4 hours post-dose. Baseline was the last SBP recorded at and within 30 minutes before intake of study drug. | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Change From Baseline in Standing Systolic Blood Pressure (SBP) Within 4 Hours Post-dose at Visit 6 (Week 12) | Systolic blood pressure (SBP) was measured as standard vital sign parameter. Range allowed in this study: <= 180 mmHg. In addition, SBP must be >=95 mmHg in the first 2 hours after intake of background treatment with sildenafil. The maximum change from baseline at each visit was defined as the within-subject maximum decrease from baseline (or zero if baseline was lower than all subsequent SBP measurements in that profile) within 4 hours post-dose. Baseline was the last SBP recorded at and within 30 minutes before intake of study drug. |
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Inclusion Criteria:
Exclusion Criteria:
Subject's participating in another clinical trial or who have done so within 30 days before Visit 1
Previous assignment to treatment during this study
Pregnant women
Subjects with a medical disorder, condition, or history of such that would impair the subject's ability to participate or complete this study in the opinion of the investigator
Subjects with substance abuse (eg alcohol or drug abuse) within the previous 180 days before Visit 1
Subjects with underlying medical disorders with an anticipated life expectancy below 2 years (eg active cancer disease with localized and/or metastasized tumor mass)
Subjects with a history of severe allergies or multiple drug allergies
Subjects with hypersensitivity to the investigational drug or any of the excipients
Subjects unable to perform a valid 6MWD test, eg subjects with a severe peripheral artery occlusive disease
Subjects with a relative difference (ie absolute difference/mean) of more than 15% between the eligibility- and the baseline 6MWD test
All types of pulmonary hypertension except subtypes of Updated Clinical Classification of pulmonary hypertension (PH) (Dana Point 2008) Group I specified in the inclusion criteria
Moderate to severe obstructive lung disease (forced expiratory volume <60% predicted). The predicted forced expiratory volume in 1 second (FEV1) is a calculated value
Severe restrictive lung disease (total lung capacity <70% predicted). The predicted total lung capacity (TLC) is a calculated value
Severe congenital abnormalities of the lungs, thorax, and diaphragm
Oxygen saturation (SaO2) <88% despite supplemental oxygen therapy
Arterial partial oxygen pressure (PaO2) <55 mmHg despite supplemental oxygen therapy
Arterial partial pressure of carbon dioxide (PaCO2) >45 mmHg
Uncontrolled arterial hypertension (SBP >180 mmHg and /or diastolic blood pressure >110 mmHg
Atrial fibrillation within the last 90 days before Visit 1
Pulmonary venous hypertension with pulmonary capillary wedge pressure 15 mmHg
Hypertrophic obstructive cardiomyopathy
Severe proven or suspected coronary artery disease
Clinical evidence of symptomatic atherosclerotic disease
Congenital or acquired valvular or myocardial disease if clinically significant apart from tricuspid valvular insufficiency due to pulmonary hypertension
Clinical relevant hepatic dysfunction indicated by:
Renal insufficiency (glomerular filtration rate <30 mL/min, eg calculated based on the Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formulas
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| Name | Affiliation | Role |
|---|---|---|
| Bayer Study Director | Bayer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aurora | Colorado | 80045 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25657022 | Result | Galie N, Muller K, Scalise AV, Grunig E. PATENT PLUS: a blinded, randomised and extension study of riociguat plus sildenafil in pulmonary arterial hypertension. Eur Respir J. 2015 May;45(5):1314-22. doi: 10.1183/09031936.00105914. Epub 2015 Feb 5. |
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24 subjects were enrolled in 11 study centers in 5 European countries. Six of the 24 subjects were screened but not randomized (screen failure [6]). 18 of the 24 participants were randomized. All of the 18 randomized participants received study medication.
Only participants with symptomatic Pulmonary arterial hypertension (PAH) could participate in this study. Subjects must be on pre-treatment with sildenafil at a dose of 20 mg three times daily (tid) (20 or 25 mg tid in New Zealand) for at least 90 days.
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| ID | Title | Description |
|---|---|---|
| FG000 | Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks. Participants continued to take daily stable sildenafil background treatment according to their prescriptions. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period |
|
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| Placebo | Drug | Placebo for 12 weeks |
|
| Sildenafil | Drug | Participants continued to take daily stable sildenafil background treatment according to their prescriptions. |
|
| Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
| Maximum Change From Baseline in Supine Diastolic Blood Pressure (DBP) Within 4 Hours Post-dose at Visit 6 (Week 12) | Diastolic blood pressure (DBP) was measured as standard vital sign parameter. Range allowed in this study: <= 110 mmHg. The maximum change from baseline at each visit was defined as the within-subject maximum decrease from baseline (or zero if baseline was lower than all subsequent DBP measurements in that profile) within 4 hours post-dose. Baseline was the last DBP recorded at and within 30 minutes before intake of study drug. | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
| Maximum Change From Baseline in Standing Diastolic Blood Pressure (DBP) Within 4 Hours Post-dose at Visit 6 (Week 12) | Diastolic blood pressure (DBP) was measured as standard vital sign parameter. Range allowed in this study: <= 110 mmHg. The maximum change from baseline at each visit was defined as the within-subject maximum decrease from baseline (or zero if baseline was lower than all subsequent DBP measurements in that profile) within 4 hours post-dose. Baseline was the last DBP recorded at and within 30 minutes before intake of study drug. | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
| Maximum Change From Baseline in Supine Heart Rate (HR) Within 4 Hours Post-dose at Visit 6 (Week 12) | Heart rate (HR) was measured as standard vital sign parameter. Range allowed in this study: <= 105 beats per minute (bpm) in the first 2 hours after intake of background treatment with sildenafil. The maximum change from baseline at each visit was defined as the within-subject maximum increase from baseline (or zero if baseline was higher than all subsequent HR measurements in that profile) within 4 hours post-dose. Baseline was the last HR recorded at and within 30 minutes before intake of study drug. | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
| Maximum Change From Baseline in Standing Heart Rate (HR) Within 4 Hours Post-dose at Visit 6 (Week 12) | Heart rate (HR) was measured as standard vital sign parameter. Range allowed in this study: <= 105 beats per minute (bpm) in the first 2 hours after intake of background treatment with sildenafil. The maximum change from baseline at each visit was defined as the within-subject maximum increase from baseline (or zero if baseline was higher than all subsequent HR measurements in that profile) within 4 hours post-dose. Baseline was the last HR recorded at and within 30 minutes before intake of study drug. | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
| Area Under Effect Curve (AUEC) of Supine SBP Within 4 Hours Post-dose at Visit 6 (Week 12) | The area under the effect curve (AUEC) at each visit of supine SBP describes an average within-subject change in SBP from baseline over a time-period of 4 hours post-dose (Note that the area only takes values below the individual baseline for the respective visit into account. The area that would result from an increase from baseline is not taken into account for the calculation of the area). Baseline was the last SBP recorded at and within 30 minutes before intake of study drug. | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
| Area Under Effect Curve (AUEC) of Standing SBP Within 4 Hours Post-dose at Visit 6 (Week 12) | The area under effect curve (AUEC) at each visit of standing SBP describes an average within-subject change in SBP from baseline over a time-period of 4 hours post-dose (Note that the area only takes values below the individual baseline for the respective visit into account. The area that would result from an increase from baseline is not taken into account for the calculation of the area). Baseline was the last SBP recorded at and within 30 minutes before intake of study drug. | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
| Area Under Effect Curve (AUEC) of Supine DBP Within 4 Hours Post-dose at Visit 6 (Week 12) | The area under effect curve (AUEC) at each visit of supine DBP describes an average within-subject change in DBP from baseline over a time-period of 4 hours post-dose (Note that the area only takes values below the individual baseline for the respective visit into account. The area that would result from an increase from baseline is not taken into account for the calculation of the area). Baseline was the last DBP recorded at and within 30 minutes before intake of study drug. | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
| Area Under Effect Curve (AUEC) of Standing DBP Within 4 Hours Post-dose at Visit 6 (Week 12) | The area under effect curve (AUEC) at each visit of standing DBP describes an average within-subject change in DBP from baseline over a time-period of 4 hours post-dose (Note that the area only takes values below the individual baseline for the respective visit into account. The area that would result from an increase from baseline is not taken into account for the calculation of the area). Baseline was the last DBP recorded at and within 30 minutes before intake of study drug. | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
| Area Under Effect Curve (AUEC) of Supine HR Within 4 Hours Post-dose at Visit 6 (Week 12) | The area under effect curve (AUEC) at each visit of supine HR describes an average within-subject change in HR from baseline over a time-period of 4 hours post-dose (Note that the area only takes values above the individual baseline for the respective visit into account. The area that would result from a decrease from baseline is not taken into account for the calculation of the area). Baseline was the last HR recorded at and within 30 minutes before intake of study drug. | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
| Area Under Effect Curve (AUEC) of Standing HR Within 4 Hours Post-dose at Visit 6 (Week 12) | The area under effect curve (AUEC) at each visit of standing HR describes an average within-subject increase in HR from baseline over a time-period of 4 hours post-dose (Note that the area only takes values above the individual baseline for the respective visit into account. The area that would result from a decrease from baseline is not taken into account for the calculation of the area). Baseline was the last HR recorded at and within 30 minutes before intake of study drug. | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
| Columbus |
| Ohio |
| 43221 |
| United States |
| Providence | Rhode Island | 02903 | United States |
| Innsbruck | 6020 | Austria |
| Villach | 9500 | Austria |
| Vseobecna fakultni nemocnice | Prague | 12808 | Czechia |
| Heidelberg | Baden-Wurttemberg | 69126 | Germany |
| Regensburg | Bavaria | 93042 | Germany |
| Würzburg | Bavaria | 97074 | Germany |
| Hamburg | Free and Hanseatic City of Hamburg | 20246 | Germany |
| Giessen | Hesse | 35392 | Germany |
| Hanover | Lower Saxony | 30625 | Germany |
| Cologne | North Rhine-Westphalia | 50924 | Germany |
| Mönchengladbach | North Rhine-Westphalia | 41063 | Germany |
| Dresden | Saxony | 01307 | Germany |
| Berlin | State of Berlin | 13353 | Germany |
| Bologna | Emilia-Romagna | 40138 | Italy |
| Pavia | Lombardy | 27100 | Italy |
| Auckland | 1051 | New Zealand |
| Christchurch | 8011 | New Zealand |
| Otwock | 05-400 | Poland |
| Warsaw | 01-138 | Poland |
| Barcelona | Barcelona | 08036 | Spain |
| Papworth Hospital | Cambridge | Cambridgeshire | CB23 3RE | United Kingdom |
| Clydebank | West Dunbartonshire | G81 4DY | United Kingdom |
| FG001 |
| Placebo |
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks. Participants continued to take daily stable sildenafil background treatment according to their prescriptions. |
| Participants Received Treatment |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Long-term Extension (LTE) Period |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks. Participants continued to take daily stable sildenafil background treatment according to their prescriptions. |
| BG001 | Placebo | Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks. Participants continued to take daily stable sildenafil background treatment according to their prescriptions. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Change From Baseline in Supine Systolic Blood Pressure (SBP) Within 4 Hours Post-dose at Visit 6 (Week 12) | Systolic blood pressure (SBP) was measured as standard vital sign parameter. Range allowed in this study: <= 180 mmHg. In addition, SBP must be >=95 mmHg in the first 2 hours after intake of background treatment with sildenafil. The maximum change from baseline at each visit was defined as the within-subject maximum decrease from baseline (or zero if baseline was lower than all subsequent SBP measurements in that profile) within 4 hours post-dose. Baseline was the last SBP recorded at and within 30 minutes before intake of study drug. | pharmacodynamic(s) (PD) analysis set | Posted | Mean | Standard Deviation | mmHg | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
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| Secondary | Maximum Change From Baseline in Standing Systolic Blood Pressure (SBP) Within 4 Hours Post-dose at Visit 6 (Week 12) | Systolic blood pressure (SBP) was measured as standard vital sign parameter. Range allowed in this study: <= 180 mmHg. In addition, SBP must be >=95 mmHg in the first 2 hours after intake of background treatment with sildenafil. The maximum change from baseline at each visit was defined as the within-subject maximum decrease from baseline (or zero if baseline was lower than all subsequent SBP measurements in that profile) within 4 hours post-dose. Baseline was the last SBP recorded at and within 30 minutes before intake of study drug. | PD analysis set | Posted | Mean | Standard Deviation | mmHg | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
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| Secondary | Maximum Change From Baseline in Supine Diastolic Blood Pressure (DBP) Within 4 Hours Post-dose at Visit 6 (Week 12) | Diastolic blood pressure (DBP) was measured as standard vital sign parameter. Range allowed in this study: <= 110 mmHg. The maximum change from baseline at each visit was defined as the within-subject maximum decrease from baseline (or zero if baseline was lower than all subsequent DBP measurements in that profile) within 4 hours post-dose. Baseline was the last DBP recorded at and within 30 minutes before intake of study drug. | PD analysis set | Posted | Mean | Standard Deviation | mmHg | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
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| Secondary | Maximum Change From Baseline in Standing Diastolic Blood Pressure (DBP) Within 4 Hours Post-dose at Visit 6 (Week 12) | Diastolic blood pressure (DBP) was measured as standard vital sign parameter. Range allowed in this study: <= 110 mmHg. The maximum change from baseline at each visit was defined as the within-subject maximum decrease from baseline (or zero if baseline was lower than all subsequent DBP measurements in that profile) within 4 hours post-dose. Baseline was the last DBP recorded at and within 30 minutes before intake of study drug. | PD analysis set | Posted | Mean | Standard Deviation | mmHg | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
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| Secondary | Maximum Change From Baseline in Supine Heart Rate (HR) Within 4 Hours Post-dose at Visit 6 (Week 12) | Heart rate (HR) was measured as standard vital sign parameter. Range allowed in this study: <= 105 beats per minute (bpm) in the first 2 hours after intake of background treatment with sildenafil. The maximum change from baseline at each visit was defined as the within-subject maximum increase from baseline (or zero if baseline was higher than all subsequent HR measurements in that profile) within 4 hours post-dose. Baseline was the last HR recorded at and within 30 minutes before intake of study drug. | PD analysis set | Posted | Mean | Standard Deviation | Beats/min | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
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| Secondary | Maximum Change From Baseline in Standing Heart Rate (HR) Within 4 Hours Post-dose at Visit 6 (Week 12) | Heart rate (HR) was measured as standard vital sign parameter. Range allowed in this study: <= 105 beats per minute (bpm) in the first 2 hours after intake of background treatment with sildenafil. The maximum change from baseline at each visit was defined as the within-subject maximum increase from baseline (or zero if baseline was higher than all subsequent HR measurements in that profile) within 4 hours post-dose. Baseline was the last HR recorded at and within 30 minutes before intake of study drug. | PD analysis set | Posted | Mean | Standard Deviation | Beats/min | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
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| Secondary | Area Under Effect Curve (AUEC) of Supine SBP Within 4 Hours Post-dose at Visit 6 (Week 12) | The area under the effect curve (AUEC) at each visit of supine SBP describes an average within-subject change in SBP from baseline over a time-period of 4 hours post-dose (Note that the area only takes values below the individual baseline for the respective visit into account. The area that would result from an increase from baseline is not taken into account for the calculation of the area). Baseline was the last SBP recorded at and within 30 minutes before intake of study drug. | PD analysis set | Posted | Mean | Standard Deviation | mmHg*h | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
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| Secondary | Area Under Effect Curve (AUEC) of Standing SBP Within 4 Hours Post-dose at Visit 6 (Week 12) | The area under effect curve (AUEC) at each visit of standing SBP describes an average within-subject change in SBP from baseline over a time-period of 4 hours post-dose (Note that the area only takes values below the individual baseline for the respective visit into account. The area that would result from an increase from baseline is not taken into account for the calculation of the area). Baseline was the last SBP recorded at and within 30 minutes before intake of study drug. | PD analysis set | Posted | Mean | Standard Deviation | mmHg*h | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
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| Secondary | Area Under Effect Curve (AUEC) of Supine DBP Within 4 Hours Post-dose at Visit 6 (Week 12) | The area under effect curve (AUEC) at each visit of supine DBP describes an average within-subject change in DBP from baseline over a time-period of 4 hours post-dose (Note that the area only takes values below the individual baseline for the respective visit into account. The area that would result from an increase from baseline is not taken into account for the calculation of the area). Baseline was the last DBP recorded at and within 30 minutes before intake of study drug. | PD analysis set | Posted | Mean | Standard Deviation | mmHg*h | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
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| Secondary | Area Under Effect Curve (AUEC) of Standing DBP Within 4 Hours Post-dose at Visit 6 (Week 12) | The area under effect curve (AUEC) at each visit of standing DBP describes an average within-subject change in DBP from baseline over a time-period of 4 hours post-dose (Note that the area only takes values below the individual baseline for the respective visit into account. The area that would result from an increase from baseline is not taken into account for the calculation of the area). Baseline was the last DBP recorded at and within 30 minutes before intake of study drug. | PD analysis set | Posted | Mean | Standard Deviation | mmHg*h | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
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| Secondary | Area Under Effect Curve (AUEC) of Supine HR Within 4 Hours Post-dose at Visit 6 (Week 12) | The area under effect curve (AUEC) at each visit of supine HR describes an average within-subject change in HR from baseline over a time-period of 4 hours post-dose (Note that the area only takes values above the individual baseline for the respective visit into account. The area that would result from a decrease from baseline is not taken into account for the calculation of the area). Baseline was the last HR recorded at and within 30 minutes before intake of study drug. | PD analysis set | Posted | Mean | Standard Deviation | Beats/min*h | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
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| Secondary | Area Under Effect Curve (AUEC) of Standing HR Within 4 Hours Post-dose at Visit 6 (Week 12) | The area under effect curve (AUEC) at each visit of standing HR describes an average within-subject increase in HR from baseline over a time-period of 4 hours post-dose (Note that the area only takes values above the individual baseline for the respective visit into account. The area that would result from a decrease from baseline is not taken into account for the calculation of the area). Baseline was the last HR recorded at and within 30 minutes before intake of study drug. | PD analysis set | Posted | Mean | Standard Deviation | Beats/min*h | Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12) |
|
Adverse event data were collected after signing the informed consent until 2 days after end of treatment with the study medication.
Participants completing the main 12-week study phase were allowed to enter a long-term extension phase receiving individual titrated Riociguat at their optimal dose. Long-term extension phase was planned to last until regulatory approval of riociguat but was prematurely terminated by the sponsor.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks. Participants continued to take daily stable sildenafil background treatment according to their prescriptions. | 7 | 12 | 12 | 12 | ||
| EG001 | Placebo | Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks. Participants continued to take daily stable sildenafil background treatment according to their prescriptions. | 2 | 6 | 6 | 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina pectoris | Cardiac disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Right ventricular failure | Cardiac disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Acute right ventricular failure | Cardiac disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Chronic right ventricular failure | Cardiac disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA (16.0) | Non-systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA (16.0) | Non-systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Loss of consciousness | Nervous system disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Chronic right ventricular failure | Cardiac disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Eye swelling | Eye disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Eyelid oedema | Eye disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Anal fissure | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Hiatus hernia | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Tongue ulceration | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Epigastric discomfort | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Regurgitation | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Oedema | General disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Inflammation | General disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Periodontitis | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Sialoadenitis | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Pharyngotonsillitis | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Peritonitis bacterial | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (16.0) | Non-systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (16.0) | Non-systematic Assessment |
| |
| Subcutaneous haematoma | Injury, poisoning and procedural complications | MedDRA (16.0) | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (16.0) | Non-systematic Assessment |
| |
| Meniscus injury | Injury, poisoning and procedural complications | MedDRA (16.0) | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Alpha 1 foetoprotein increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Blood cholinesterase decreased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Blood potassium decreased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Blood pressure systolic decreased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Glomerular filtration rate decreased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Neutrophil count increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Glutamate dehydrogenase increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Renal failure chronic | Renal and urinary disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Bronchitis chronic | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Nasal obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Cataract operation | Surgical and medical procedures | MedDRA (16.0) | Non-systematic Assessment |
| |
| Capillary fragility | Vascular disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (16.0) | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (16.0) | Non-systematic Assessment |
|
The embargo can be up to 6 months (equal to the 180 days), moreover if it is necessary the embargo period can be prolonged to expiry of priority year.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Therapeutic Area Head | Bayer | clinical-trials-contact@bayerhealthcare.com |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C542595 | riociguat |
| D000068677 | Sildenafil Citrate |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
Not provided
Not provided
| Adverse Event |
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