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Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02283762
Recruitment Status : Completed
First Posted : November 5, 2014
Results First Posted : January 25, 2019
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Scleroderma, Systemic
Interventions Drug: Riociguat (Adempas, BAY63-2521)
Drug: Placebo
Enrollment 121
Recruitment Details The Main Treatment Phase of the study has been conducted between 15 Jan 2015 (first subject first visit) and 03 Jan 2018 (last subject last visit for the main treatment phase). Overall, 68 study centers in 16 countries have been ready to enroll. Of these, 60 in 15 countries enrolled >= 1 patient.
Pre-assignment Details 139 participants were screened in 60 study centers in 15 countries worldwide. 18 participants were not randomized / treated. 121 participants were randomized and treated with at least one dose of study medication. Only data for the Main Treatment Phase was presented in Participant flow.
Arm/Group Title Riociguat (Adempas, BAY63-2521) Placebo
Hide Arm/Group Description Main treatment phase of 52 weeks: participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a-titration period of up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received sham-titration in a dose-titration period of up to 10 weeks followed by a maintenance period. Main treatment phase of 52 weeks: participants received matching placebo tablets to riociguat as sham-titration in a dose-titration period up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a dose-titration period of up to 10 weeks followed by a maintenance period.
Period Title: Overall Study
Started 60 61
Completed 42 46
Not Completed 18 15
Reason Not Completed
Adverse Event             9             9
Lack of Efficacy             1             0
Physician Decision             1             1
Pregnancy             0             1
Withdrawal by Subject             7             4
Arm/Group Title Riociguat (Adempas, BAY63-2521) Placebo Total
Hide Arm/Group Description Main treatment phase of 52 weeks: participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a-titration period of up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received sham-titration in a dose-titration period of up to 10 weeks followed by a maintenance period. Main treatment phase of 52 weeks: participants received matching placebo tablets to riociguat as sham-titration in a dose-titration period up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a dose-titration period of up to 10 weeks followed by a maintenance period. Total of all reporting groups
Overall Number of Baseline Participants 60 61 121
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 60 participants 61 participants 121 participants
51.9  (11.5) 49.5  (12.9) 50.7  (12.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants 61 participants 121 participants
Female
47
  78.3%
45
  73.8%
92
  76.0%
Male
13
  21.7%
16
  26.2%
29
  24.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 60 participants 61 participants 121 participants
White 43 46 89
Black 2 3 5
Asian 12 12 24
Native Hawaiian or other pacific islander 1 0 1
Not Hispanic or Latino 59 58 117
Modified Rodnan skin score (mRSS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 60 participants 61 participants 121 participants
16.9  (3.4) 16.7  (4.1) 16.8  (3.7)
[1]
Measure Description: The mRSS is a validated physical examination method for estimating skin thickness. It correlates with biopsy measures of collagen in the dermis and reflects prognosis and visceral involvement, especially in early disease. It is scored on 0 (normal) to 3+ (severe induration) ordinal scales over 17 body areas, with a maximum score of 51 (higher score means worse situation) and is used to categorize severity of systemic sclerosis (SSc).
Forced vital capacity (FVC) percent predicted   [1] 
Mean (Standard Deviation)
Unit of measure:  FVC percent predicted
Number Analyzed 60 participants 61 participants 121 participants
90.743  (18.523) 94.823  (17.034) 92.800  (17.832)
[1]
Measure Description: Pulmonary function tests included forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO). FVC percent predicted was reported.
1.Primary Outcome
Title Change From Baseline in Modified Rodnan Skin Score (mRSS) to Week 52
Hide Description The mRSS is a validated physical examination method for estimating skin thickness. It correlates with biopsy measures of collagen in the dermis and reflects prognosis and visceral involvement, especially in early disease. It is scored on 0 (normal) to 3+ (severe induration) ordinal scales over 17 body areas, with a maximum score of 51 (higher score means worse situation) and is used to categorize severity of SSc. A decrease in the mean change of mRSS shows mRSS improved.
Time Frame Baseline to week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS: all participants randomized and treated with study medication) with evaluable data for this outcome measure.
Arm/Group Title Riociguat (Adempas, BAY63-2521) Placebo
Hide Arm/Group Description:
Main treatment phase of 52 weeks: participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a-titration period of up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received sham-titration in a dose-titration period of up to 10 weeks followed by a maintenance period.
Main treatment phase of 52 weeks: participants received matching placebo tablets to riociguat as sham-titration in a dose-titration period up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a dose-titration period of up to 10 weeks followed by a maintenance period.
Overall Number of Participants Analyzed 57 52
Mean (Standard Deviation)
Unit of Measure: score on a scale
-2.088  (5.658) -0.769  (8.243)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0815
Comments [Not Specified]
Method MMRM (Method 1)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of LS means
Estimated Value -2.34
Confidence Interval (2-Sided) 95%
-4.99 to 0.30
Estimation Comments [Not Specified]
2.Secondary Outcome
Title CRISS (American College of Rheumatology Composite Response Index for Clinical Trials) at Week 52 Reported as Number of Participants With a CRISS Probability >=0.60 or <0.60 From Baseline to Week 52
Hide Description CRISS forms a composite response index consisting of SSc-related organ involvement and the following five variables: mRSS, FVC percent predicted, physician’s and patient’s global assessments, and HAQ-DI score (from SHAQ patient-reported outcome). The resulting index is a 2-step process that captures clinically meaningful worsening of internal organ involvement and the core variables that show change. Patients for whom the predicted CRISS probability was ≥ 0.60 were considered improved, while patients for whom the predicted probability was < 0.60 were considered not improved.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title Riociguat (Adempas, BAY63-2521) Placebo
Hide Arm/Group Description:
Main treatment phase of 52 weeks: participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a-titration period of up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received sham-titration in a dose-titration period of up to 10 weeks followed by a maintenance period.
Main treatment phase of 52 weeks: participants received matching placebo tablets to riociguat as sham-titration in a dose-titration period up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a dose-titration period of up to 10 weeks followed by a maintenance period.
Overall Number of Participants Analyzed 60 61
Measure Type: Count of Participants
Unit of Measure: Participants
CRISS probability ≥ 0.60
11
  18.3%
11
  18.0%
CRISS probability < 0.60
49
  81.7%
50
  82.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The pre-specified test was for superiority but ONLY if the primary endpoint and preceding secondary endpoints were meeting statistical significance (hierarchical testing).
Statistical Test of Hypothesis P-Value 0.9770
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter %
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-13.68 to 14.09
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score to Week 52
Hide Description The HAQ-DI is a composite measure from which a ‘Standard Disability Index’ score can be computed to assess a patient’s disability level. Generally, a score of 0–1 represents mild to moderate difficulty, 1–2 moderate to severe disability and 2–3 severe to very severe disability. The HAQ-DI comprises 20 items that assess patient abilities across 8 functional activities: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item is rated on a 4-point scale: 0=Without ANY difficulty, 1=With SOME difficulty, 2=With MUCH difficulty, 3=UNABLE to do. The 8 scores of the 8 sections are summed and divided by 8. In the event that one section is not completed by a subject then the summed score would be divided by 7. The final overall HAQ-DI score ranges from 0 to 3 and positive change indicates worse health-related quality of life (HRQoL).
Time Frame Baseline to week 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with evaluable data for this outcome measure.
Arm/Group Title Riociguat (Adempas, BAY63-2521) Placebo
Hide Arm/Group Description:
Main treatment phase of 52 weeks: participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a-titration period of up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received sham-titration in a dose-titration period of up to 10 weeks followed by a maintenance period.
Main treatment phase of 52 weeks: participants received matching placebo tablets to riociguat as sham-titration in a dose-titration period up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a dose-titration period of up to 10 weeks followed by a maintenance period.
Overall Number of Participants Analyzed 60 61
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 60 participants 61 participants
0.888  (0.665) 0.693  (0.688)
Change from baseline Number Analyzed 56 participants 52 participants
0.054  (0.381) 0.127  (0.418)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521), Placebo
Comments change from baseline
Type of Statistical Test Superiority
Comments The pre-specified test was for superiority but ONLY if the primary endpoint and preceding secondary endpoints were meeting statistical significance (hierarchical testing).
Statistical Test of Hypothesis P-Value 0.3529
Comments [Not Specified]
Method MMRM (Method 1)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.23 to 0.08
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Patient’s Global Assessment Score to Week 52
Hide Description The patient’s global assessments (a self-report) quantified the overall disease activity or severity of SSc, with scores ranging from 0 (good) to 10 (worse). Positive change in the patient’s global assessments score indicates worsening.
Time Frame Baseline to week 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with evaluable data for this outcome measure.
Arm/Group Title Riociguat (Adempas, BAY63-2521) Placebo
Hide Arm/Group Description:
Main treatment phase of 52 weeks: participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a-titration period of up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received sham-titration in a dose-titration period of up to 10 weeks followed by a maintenance period.
Main treatment phase of 52 weeks: participants received matching placebo tablets to riociguat as sham-titration in a dose-titration period up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a dose-titration period of up to 10 weeks followed by a maintenance period.
Overall Number of Participants Analyzed 60 61
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 60 participants 61 participants
3.933  (2.497) 3.770  (2.341)
Change from baseline Number Analyzed 45 participants 46 participants
0.689  (2.745) -0.022  (2.226)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521), Placebo
Comments Change from baseline
Type of Statistical Test Superiority
Comments The pre-specified test was for superiority but ONLY if the primary endpoint and preceding secondary endpoints were meeting statistical significance (hierarchical testing).
Statistical Test of Hypothesis P-Value 0.0887
Comments [Not Specified]
Method MMRM (Method 1)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
-0.12 to 1.69
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Physician’s Global Assessment Score to Week 52
Hide Description The physician’s global assessments (reported by the physician) quantified the overall disease activity or severity of SSc, with scores ranging from 0 (good) to 10 (worse). Positive change in the physician’s global assessments score indicates worsening.
Time Frame Baseline to week 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with evaluable data for this outcome measure.
Arm/Group Title Riociguat (Adempas, BAY63-2521) Placebo
Hide Arm/Group Description:
Main treatment phase of 52 weeks: participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a-titration period of up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received sham-titration in a dose-titration period of up to 10 weeks followed by a maintenance period.
Main treatment phase of 52 weeks: participants received matching placebo tablets to riociguat as sham-titration in a dose-titration period up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a dose-titration period of up to 10 weeks followed by a maintenance period.
Overall Number of Participants Analyzed 60 61
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 60 participants 61 participants
4.333  (2.105) 4.016  (2.004)
Change from baseline Number Analyzed 45 participants 47 participants
-0.067  (2.157) -0.745  (2.090)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521), Placebo
Comments Change from baseline
Type of Statistical Test Superiority
Comments The pre-specified test was for superiority but ONLY if the primary endpoint and preceding secondary endpoints were meeting statistical significance (hierarchical testing).
Statistical Test of Hypothesis P-Value 0.0241
Comments [Not Specified]
Method MMRM (Method 1)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.11 to 1.54
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted to Week 52
Hide Description Negative change in FVC percent predicted indicates worsening.
Time Frame Baseline to week 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with evaluable data for this outcome measure.
Arm/Group Title Riociguat (Adempas, BAY63-2521) Placebo
Hide Arm/Group Description:
Main treatment phase of 52 weeks: participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a-titration period of up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received sham-titration in a dose-titration period of up to 10 weeks followed by a maintenance period.
Main treatment phase of 52 weeks: participants received matching placebo tablets to riociguat as sham-titration in a dose-titration period up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a dose-titration period of up to 10 weeks followed by a maintenance period.
Overall Number of Participants Analyzed 55 51
Mean (Standard Deviation)
Unit of Measure: FVC percent predicted
-2.376  (7.515) -2.945  (9.727)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521), Placebo
Comments change from baseline
Type of Statistical Test Superiority
Comments The pre-specified test was for superiority but ONLY if the primary endpoint and preceding secondary endpoints were meeting statistical significance (hierarchical testing).
Statistical Test of Hypothesis P-Value 0.9010
Comments [Not Specified]
Method MMRM (Method 1)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-3.40 to 3.00
Estimation Comments [Not Specified]
Time Frame From first application of study drug up to 2 days after end of treatment with study drug, approximately 1 year of treatment in the Main Treatment Phase of the study.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Riociguat (Adempas, BAY63-2521) Placebo
Hide Arm/Group Description Main treatment phase of 52 weeks: participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a-titration period of up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received sham-titration in a dose-titration period of up to 10 weeks followed by a maintenance period. Main treatment phase of 52 weeks: participants received matching placebo tablets to riociguat as sham-titration in a dose-titration period up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a dose-titration period of up to 10 weeks followed by a maintenance period.
All-Cause Mortality
Riociguat (Adempas, BAY63-2521) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/60 (1.67%)      1/61 (1.64%)    
Show Serious Adverse Events Hide Serious Adverse Events
Riociguat (Adempas, BAY63-2521) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/60 (15.00%)      15/61 (24.59%)    
Blood and lymphatic system disorders     
Anaemia * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Cardiac disorders     
Angina pectoris * 1  1/60 (1.67%)  1 1/61 (1.64%)  1
Atrial fibrillation * 1  1/60 (1.67%)  2 0/61 (0.00%)  0
Left ventricular failure * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Pericarditis * 1  0/60 (0.00%)  0 2/61 (3.28%)  2
Ventricular tachycardia * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Gastrointestinal disorders     
Abdominal pain * 1  1/60 (1.67%)  3 0/61 (0.00%)  0
Gastric haemorrhage * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Gastrooesophageal reflux disease * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Intestinal pseudo-obstruction * 1  1/60 (1.67%)  1 0/61 (0.00%)  0
Nausea * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Vomiting * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
General disorders     
Inflammation * 1  1/60 (1.67%)  1 0/61 (0.00%)  0
Infections and infestations     
Infected skin ulcer * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Pneumonia * 1  1/60 (1.67%)  1 2/61 (3.28%)  2
Lung infection * 1  1/60 (1.67%)  1 0/61 (0.00%)  0
Injury, poisoning and procedural complications     
Exposure during pregnancy * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Musculoskeletal and connective tissue disorders     
Osteolysis * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Pain in extremity * 1  1/60 (1.67%)  1 0/61 (0.00%)  0
Scleroderma * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Musculoskeletal discomfort * 1  1/60 (1.67%)  1 0/61 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Adenocarcinoma gastric * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Ovarian cancer * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Intraductal proliferative breast lesion * 1  1/60 (1.67%)  1 0/61 (0.00%)  0
Nervous system disorders     
Cerebellar infarction * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Syncope * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Renal and urinary disorders     
Scleroderma renal crisis * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Dyspnoea * 1  1/60 (1.67%)  1 0/61 (0.00%)  0
Skin and subcutaneous tissue disorders     
Skin ulcer * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Surgical and medical procedures     
Prophylaxis * 1  0/60 (0.00%)  0 1/61 (1.64%)  1
Vascular disorders     
Raynaud's phenomenon * 1  1/60 (1.67%)  1 1/61 (1.64%)  1
1
Term from vocabulary, MedDRA (20.1)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Riociguat (Adempas, BAY63-2521) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   54/60 (90.00%)      48/61 (78.69%)    
Cardiac disorders     
Palpitations * 1  8/60 (13.33%)  8 3/61 (4.92%)  3
Gastrointestinal disorders     
Abdominal distension * 1  4/60 (6.67%)  5 1/61 (1.64%)  1
Abdominal pain * 1  2/60 (3.33%)  2 5/61 (8.20%)  5
Constipation * 1  3/60 (5.00%)  3 4/61 (6.56%)  4
Diarrhoea * 1  10/60 (16.67%)  15 8/61 (13.11%)  11
Dry mouth * 1  4/60 (6.67%)  4 1/61 (1.64%)  1
Dyspepsia * 1  7/60 (11.67%)  7 2/61 (3.28%)  2
Dysphagia * 1  6/60 (10.00%)  7 1/61 (1.64%)  1
Gastrooesophageal reflux disease * 1  15/60 (25.00%)  16 7/61 (11.48%)  7
Nausea * 1  7/60 (11.67%)  9 6/61 (9.84%)  6
Vomiting * 1  8/60 (13.33%)  14 6/61 (9.84%)  8
General disorders     
Asthenia * 1  3/60 (5.00%)  6 3/61 (4.92%)  4
Fatigue * 1  7/60 (11.67%)  7 6/61 (9.84%)  7
Oedema peripheral * 1  6/60 (10.00%)  7 2/61 (3.28%)  2
Pain * 1  3/60 (5.00%)  4 0/61 (0.00%)  0
Pyrexia * 1  2/60 (3.33%)  2 4/61 (6.56%)  4
Peripheral swelling * 1  5/60 (8.33%)  6 5/61 (8.20%)  5
Infections and infestations     
Bronchitis * 1  3/60 (5.00%)  3 1/61 (1.64%)  1
Nasopharyngitis * 1  5/60 (8.33%)  7 5/61 (8.20%)  8
Upper respiratory tract infection * 1  4/60 (6.67%)  5 8/61 (13.11%)  10
Urinary tract infection * 1  4/60 (6.67%)  5 2/61 (3.28%)  2
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  12/60 (20.00%)  14 8/61 (13.11%)  9
Back pain * 1  3/60 (5.00%)  3 4/61 (6.56%)  4
Muscle spasms * 1  4/60 (6.67%)  6 0/61 (0.00%)  0
Pain in extremity * 1  4/60 (6.67%)  6 2/61 (3.28%)  2
Nervous system disorders     
Dizziness * 1  13/60 (21.67%)  21 7/61 (11.48%)  7
Headache * 1  11/60 (18.33%)  12 12/61 (19.67%)  16
Paraesthesia * 1  1/60 (1.67%)  1 4/61 (6.56%)  5
Psychiatric disorders     
Insomnia * 1  3/60 (5.00%)  3 2/61 (3.28%)  2
Respiratory, thoracic and mediastinal disorders     
Cough * 1  9/60 (15.00%)  9 5/61 (8.20%)  5
Dyspnoea * 1  8/60 (13.33%)  9 5/61 (8.20%)  6
Epistaxis * 1  4/60 (6.67%)  5 2/61 (3.28%)  2
Interstitial lung disease * 1  4/60 (6.67%)  4 2/61 (3.28%)  2
Skin and subcutaneous tissue disorders     
Eczema * 1  0/60 (0.00%)  0 4/61 (6.56%)  4
Erythema * 1  3/60 (5.00%)  4 0/61 (0.00%)  0
Pruritus * 1  5/60 (8.33%)  6 5/61 (8.20%)  9
Rash * 1  3/60 (5.00%)  4 2/61 (3.28%)  2
Skin ulcer * 1  4/60 (6.67%)  4 7/61 (11.48%)  9
Vascular disorders     
Hypertension * 1  0/60 (0.00%)  0 4/61 (6.56%)  4
Hypotension * 1  7/60 (11.67%)  7 4/61 (6.56%)  4
1
Term from vocabulary, MedDRA (20.1)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Any proposed publications should be sent to Bayer for review at least 40 days before forwarding to any person that is not bound by the confidentially obligations. Bayer may request delay of publication for no more than 120 days to allow for filing Patent Applications (if applicable). No publication of single center data should be done prior to publication of multicenter data.
Results Point of Contact
Name/Title: Therapeutic Area Head
Organization: Bayer
Phone: +1 888-8422937
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02283762     History of Changes
Other Study ID Numbers: 16277
2014-001353-16 ( EudraCT Number )
First Submitted: November 3, 2014
First Posted: November 5, 2014
Results First Submitted: December 13, 2018
Results First Posted: January 25, 2019
Last Update Posted: April 17, 2019