Back to resultsEvaluation of the Pharmacodynamic Effect of the Combination of Sildenafil and Riociguat on Blood Pressure and Other Safety Parameters. (PATENT PLUS)
Primary Purpose
Pulmonary Hypertension
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Riociguat (Adempas, BAY63-2521)
Placebo
Sildenafil
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Hypertension focused on measuring Pulmonary Hypertension, Riociguat, Blood Pressure
Eligibility Criteria
Inclusion Criteria:
- 18 to 75 years of age at Visit 1
- Male and female subjects with symptomatic PAH (Group I Dana Point Updated Clinical Classification 2008), a 6-min walking distance (6MWD) of more than 150 m, a pulmonary vascular resistance (PVR) >300 dyn*s*cm-5, and a mean pulmonary artery pressure (PAPmean) ≥ 25 mmHg
- For Study Part 1: subjects on stable pretreatment with sildenafil at a dose of 20 mg tid
- Unspecific treatments which may also be used for the treatment of PAH such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. However, treatment with anticoagulants (if indicated) must have been started at least 30 days before Visit 1 and treatment with diuretics needs to be stable for at least 30 days before Visit 1
- Subjects with supplemental long-term oxygen therapy may be included, if the amount of supplemental oxygen and the delivery method was stable on average for at least 90 days before Visit 1
- SBP >/=95 mmHg and heart rate (HR) </=105 beats per minute (BPM) in the first 2 h after intake of sildenafil (measured at Visits 0 and 1)
- Women without child-bearing potential
- Subjects who are able to understand and follow instructions and who are able to participate in the study for the entire period
- Subjects must have given their written informed consent to participate in the study after having received adequate previous information and prior to any study-specific procedures
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:
- Bilirubin >2 times upper limit normal (ULN)
- and/or ALT (alanine aminotransferase) or AST (aspartate aminotransferase) >3 times ULN
- and/or signs of severe hepatic insufficiency (eg impaired albumin synthesis with an albumin <32 g/L, hepatic encephalopathy > grade 1
- Renal insufficiency (glomerular filtration rate <30 mL/min, eg calculated based on the Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formulas
Sites / Locations
- Vseobecna fakultni nemocnice
- Papworth Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01179334
Brief Title
Evaluation of the Pharmacodynamic Effect of the Combination of Sildenafil and Riociguat on Blood Pressure and Other Safety Parameters.
Acronym
PATENT PLUS
Official Title
An Interaction Study to Evaluate Changes in Blood Pressure Following 1, 1.5, 2, and 2.5 mg Riociguat Tid (Dose Titration) Compared to Placebo Treatment on the Background of Stable Sildenafil Pretreatment in Subjects With Symptomatic Pulmonary Arterial Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
May 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Hypertension
Keywords
Pulmonary Hypertension, Riociguat, Blood Pressure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Riociguat (Adempas, BAY63-2521)
Intervention Description
BAY63-2521: 1 mg tid - 2,5 mg tid oral for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Sildenafil
Intervention Description
Participants continued to take daily stable sildenafil background treatment according to their prescriptions.
Primary Outcome Measure Information:
Title
Maximum Change From Baseline in Supine Systolic Blood Pressure (SBP) Within 4 Hours Post-dose at Visit 6 (Week 12)
Description
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.
Time Frame
Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)
Secondary Outcome Measure Information:
Title
Maximum Change From Baseline in Standing Systolic Blood Pressure (SBP) Within 4 Hours Post-dose at Visit 6 (Week 12)
Description
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.
Time Frame
Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)
Title
Maximum Change From Baseline in Supine Diastolic Blood Pressure (DBP) Within 4 Hours Post-dose at Visit 6 (Week 12)
Description
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.
Time Frame
Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)
Title
Maximum Change From Baseline in Standing Diastolic Blood Pressure (DBP) Within 4 Hours Post-dose at Visit 6 (Week 12)
Description
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.
Time Frame
Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)
Title
Maximum Change From Baseline in Supine Heart Rate (HR) Within 4 Hours Post-dose at Visit 6 (Week 12)
Description
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.
Time Frame
Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)
Title
Maximum Change From Baseline in Standing Heart Rate (HR) Within 4 Hours Post-dose at Visit 6 (Week 12)
Description
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.
Time Frame
Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)
Title
Area Under Effect Curve (AUEC) of Supine SBP Within 4 Hours Post-dose at Visit 6 (Week 12)
Description
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.
Time Frame
Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)
Title
Area Under Effect Curve (AUEC) of Standing SBP Within 4 Hours Post-dose at Visit 6 (Week 12)
Description
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.
Time Frame
Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)
Title
Area Under Effect Curve (AUEC) of Supine DBP Within 4 Hours Post-dose at Visit 6 (Week 12)
Description
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.
Time Frame
Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)
Title
Area Under Effect Curve (AUEC) of Standing DBP Within 4 Hours Post-dose at Visit 6 (Week 12)
Description
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.
Time Frame
Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)
Title
Area Under Effect Curve (AUEC) of Supine HR Within 4 Hours Post-dose at Visit 6 (Week 12)
Description
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.
Time Frame
Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)
Title
Area Under Effect Curve (AUEC) of Standing HR Within 4 Hours Post-dose at Visit 6 (Week 12)
Description
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.
Time Frame
Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 to 75 years of age at Visit 1
Male and female subjects with symptomatic PAH (Group I Dana Point Updated Clinical Classification 2008), a 6-min walking distance (6MWD) of more than 150 m, a pulmonary vascular resistance (PVR) >300 dyn*s*cm-5, and a mean pulmonary artery pressure (PAPmean) ≥ 25 mmHg
For Study Part 1: subjects on stable pretreatment with sildenafil at a dose of 20 mg tid
Unspecific treatments which may also be used for the treatment of PAH such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. However, treatment with anticoagulants (if indicated) must have been started at least 30 days before Visit 1 and treatment with diuretics needs to be stable for at least 30 days before Visit 1
Subjects with supplemental long-term oxygen therapy may be included, if the amount of supplemental oxygen and the delivery method was stable on average for at least 90 days before Visit 1
SBP >/=95 mmHg and heart rate (HR) </=105 beats per minute (BPM) in the first 2 h after intake of sildenafil (measured at Visits 0 and 1)
Women without child-bearing potential
Subjects who are able to understand and follow instructions and who are able to participate in the study for the entire period
Subjects must have given their written informed consent to participate in the study after having received adequate previous information and prior to any study-specific procedures
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:
Bilirubin >2 times upper limit normal (ULN)
and/or ALT (alanine aminotransferase) or AST (aspartate aminotransferase) >3 times ULN
and/or signs of severe hepatic insufficiency (eg impaired albumin synthesis with an albumin <32 g/L, hepatic encephalopathy > grade 1
Renal insufficiency (glomerular filtration rate <30 mL/min, eg calculated based on the Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formulas
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43221
Country
United States
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
City
Villach
ZIP/Postal Code
9500
Country
Austria
Facility Name
Vseobecna fakultni nemocnice
City
Praha 2
ZIP/Postal Code
12808
Country
Czech Republic
City
Heidelberg
State/Province
Baden-Württemberg
ZIP/Postal Code
69126
Country
Germany
City
Regensburg
State/Province
Bayern
ZIP/Postal Code
93042
Country
Germany
City
Würzburg
State/Province
Bayern
ZIP/Postal Code
97074
Country
Germany
City
Gießen
State/Province
Hessen
ZIP/Postal Code
35392
Country
Germany
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
City
Köln
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
50924
Country
Germany
City
Mönchengladbach
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
41063
Country
Germany
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany
City
Berlin
ZIP/Postal Code
13353
Country
Germany
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
City
Pavia
State/Province
Lombardia
ZIP/Postal Code
27100
Country
Italy
City
Auckland
ZIP/Postal Code
1051
Country
New Zealand
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
City
Otwock
ZIP/Postal Code
05-400
Country
Poland
City
Warszawa
ZIP/Postal Code
01-138
Country
Poland
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Papworth Hospital
City
Cambridge
State/Province
Cambridgeshire
ZIP/Postal Code
CB23 3RE
Country
United Kingdom
City
Clydebank
State/Province
West Dunbartonshire
ZIP/Postal Code
G81 4DY
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
25657022
Citation
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.
Results Reference
result
Learn more about this trial
Evaluation of the Pharmacodynamic Effect of the Combination of Sildenafil and Riociguat on Blood Pressure and Other Safety Parameters.
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