Phase IIb Safety and Efficacy Study of Four Dose Regimens of BAY1021189 in Patients With Heart Failure and Preserved Ejection Fraction Suffering From Worsening Chronic Heart Failure (SOCRATES-PRESERVED)
Study Details
Study Description
Brief Summary
Objective of the study is to find the optimal dose of the once daily oral soluble guanylate cyclase stimulator (sGC) BAY1021189 for Phase III that can be given in addition to standard diuretic and comorbidity treatment for heart failure with preserved ejection fraction (HFpEF)
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Vericiguat (BAY1021189)(10 mg) 2.5 mg orally once daily for 2 weeks, up-titration to 5 mg orally once daily for 2 weeks, up-titration to 10 mg orally once daily for 8 weeks |
Drug: Vericiguat (BAY1021189) (1.25 mg)
1.25 mg BAY1021189 tablets
Drug: Vericiguat (BAY1021189) (5 mg)
5 mg BAY1021189 tablets
|
Experimental: Vericiguat (BAY1021189) (5 mg) 2.5 mg orally once daily for 2 weeks, then 5 mg orally once daily for 10 weeks (with sham titration) |
Drug: Vericiguat (BAY1021189) (1.25 mg)
1.25 mg BAY1021189 tablets
Drug: Vericiguat (BAY1021189) (5 mg)
5 mg BAY1021189 tablets
|
Experimental: Vericiguat (BAY1021189) (2.5 mg) 2.5 mg orally once daily for 12 weeks (with sham titrations) |
Drug: Vericiguat (BAY1021189) (1.25 mg)
1.25 mg BAY1021189 tablets
|
Experimental: Vericiguat (BAY1021189) (1.25 mg) 1.25 mg orally once daily for 12 weeks (with sham titrations) |
Drug: Vericiguat (BAY1021189) (1.25 mg)
1.25 mg BAY1021189 tablets
|
Placebo Comparator: Placebo Orally once daily for 12 weeks (with sham titrations) |
Drug: Placebo
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline to Week 12 in Log-transformed N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) [Baseline, Week 12 (end of treatment [EOT])]
NTproBNP is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure (HF).
- Change From Baseline to Week 12 in Left Atrial Volume (LAV) [Baseline, Week 12 (EOT)]
Left atrial volume was measured by echocardiography.
Other Outcome Measures
- Change From Baseline to Week 12 Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Baseline, Week 12 (EOT)]
Blood pressure was measured after at least 10 minutes resting in a sitting position (3 measurements taken approximately 2 minutes apart).The changes in blood pressure were recorded and the mean of the three measurements was analyzed.
- Change From Baseline to Week 12 in Heart Rate [Baseline, Week 12 (EOT)]
Heart rate was measured after 10 minutes resting in a sitting position (3 measurements taken approximatly 2 minutes apart). The changes in heart rate were recorded and the mean of the three measurements was analyzed.
- Number of Subjects With Clinical Events (Heart Failure Hospitalization and Cardio-vascular [CV] Mortality) [Baseline up to Week 16 including 12 week treatment period and 4 week follow-up period]
Clinical events (heart failure and mortality) were analyzed as CV death, and HF hospitalization at specified time points.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Worsening chronic heart failure (WCHF) requiring hospitalization (or intravenous diuretic treatment for HF without hospitalization) with initiation of study treatment after clinical stabilization
-
Left ventricular ejection fraction (LVEF) >/= 45% by echocardiography at randomization
Exclusion Criteria:
- Intravenous inotropes at any time after hospitalization
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Fountain Valley | California | United States | 92708 | |
2 | Fort Lauderdale | Florida | United States | 33308 | |
3 | Naples | Florida | United States | 34102 | |
4 | Macon | Georgia | United States | 31201 | |
5 | Chicago | Illinois | United States | 60611-2908 | |
6 | Iowa City | Iowa | United States | 52242 | |
7 | New Orleans | Louisiana | United States | 70112-1396 | |
8 | Detroit | Michigan | United States | 48202 | |
9 | Minneapolis | Minnesota | United States | 55422 | |
10 | Jackson | Mississippi | United States | 39216-4505 | |
11 | Newark | New Jersey | United States | 07103 | |
12 | Buffalo | New York | United States | 14215 | |
13 | Pittsburgh | Pennsylvania | United States | 15212 | |
14 | Charleston | South Carolina | United States | 29425 | |
15 | Germantown | Tennessee | United States | 38138 | |
16 | Nashville | Tennessee | United States | 37232-8802 | |
17 | Milwaukee | Wisconsin | United States | 53215 | |
18 | Darlinghurst | New South Wales | Australia | 2010 | |
19 | Brisbane | Queensland | Australia | 4029 | |
20 | Brisbane | Queensland | Australia | 4064 | |
21 | Redcliffe | Queensland | Australia | 4020 | |
22 | Hobart | Tasmania | Australia | 7000 | |
23 | St. Pölten | Niederösterreich | Austria | 3100 | |
24 | Linz | Oberösterreich | Austria | 4010 | |
25 | Linz | Oberösterreich | Austria | 4020 | |
26 | Graz | Steiermark | Austria | 8036 | |
27 | Salzburg | Austria | 5020 | ||
28 | Wien | Austria | 1090 | ||
29 | Wien | Austria | 1220 | ||
30 | Brugge | Belgium | 8000 | ||
31 | Bruxelles - Brussel | Belgium | 1200 | ||
32 | Gent | Belgium | 9000 | ||
33 | Gilly | Belgium | 6060 | ||
34 | HUY | Belgium | 4500 | ||
35 | Mechelen | Belgium | 2800 | ||
36 | MOL | Belgium | 2400 | ||
37 | Roeselare | Belgium | 8800 | ||
38 | Burgas | Bulgaria | 8018 | ||
39 | Sofia | Bulgaria | 1202 | ||
40 | Sofia | Bulgaria | 1233 | ||
41 | Sofia | Bulgaria | 1309 | ||
42 | Sofia | Bulgaria | 1527 | ||
43 | Stara Zagora | Bulgaria | 6000 | ||
44 | Toronto | Ontario | Canada | M5B 1W8 | |
45 | Montreal | Quebec | Canada | H1T 1C8 | |
46 | Montreal | Quebec | Canada | H2W 1T8 | |
47 | Saint-Jean-sur-Richelieu | Quebec | Canada | J3A 1C3 | |
48 | Sherbrooke | Quebec | Canada | J1G 2E8 | |
49 | Quebec | Canada | G1V 4G5 | ||
50 | Kromeriz | Czechia | 767 01 | ||
51 | Praha 10 | Czechia | 10034 | ||
52 | Praha 2 | Czechia | 12808 | ||
53 | Praha 4 | Czechia | 140 21 | ||
54 | Praha 6 | Czechia | 169 02 | ||
55 | Aalborg | Denmark | 9000 | ||
56 | Holbaek | Denmark | 4300 | ||
57 | Randers | Denmark | 8930 | ||
58 | BRON Cedex | France | 69677 | ||
59 | Pessac | France | 33604 | ||
60 | Rouen | France | 76031 | ||
61 | Toulouse | France | 31403 | ||
62 | Bad Krozingen | Baden-Württemberg | Germany | 79189 | |
63 | München | Bayern | Germany | 80331 | |
64 | Bad Homburg | Hessen | Germany | 61348 | |
65 | Greifswald | Mecklenburg-Vorpommern | Germany | 17475 | |
66 | Hannover | Niedersachsen | Germany | 30625 | |
67 | Köln | Nordrhein-Westfalen | Germany | 50937 | |
68 | Münster | Nordrhein-Westfalen | Germany | 48149 | |
69 | Homburg | Saarland | Germany | 66421 | |
70 | Erfurt | Thüringen | Germany | 99089 | |
71 | Hamburg | Germany | 20246 | ||
72 | Athens | Greece | 11527 | ||
73 | Chaidari | Greece | 12462 | ||
74 | Nea Ionia / Athens | Greece | 142 33 | ||
75 | Budapest | Hungary | 1097 | ||
76 | Kistarcsa | Hungary | H-2143 | ||
77 | Szekesfehervar | Hungary | 8000 | ||
78 | Afula | Israel | 1834111 | ||
79 | Ashkelon | Israel | 7830604 | ||
80 | Hadera | Israel | 3810101 | ||
81 | Haifa | Israel | 3109601 | ||
82 | Jerusalem | Israel | 9103102 | ||
83 | Petah Tikva | Israel | 4941492 | ||
84 | Rehovot | Israel | 7610001 | ||
85 | Tel Aviv | Israel | 6423906 | ||
86 | Tiberias | Israel | 1528001 | ||
87 | Zrifin | Israel | 7030000 | ||
88 | Bergamo | Lombardia | Italy | 24127 | |
89 | Brescia | Lombardia | Italy | 25123 | |
90 | Milano | Lombardia | Italy | 20017 | |
91 | Milano | Lombardia | Italy | 20149 | |
92 | Pavia | Lombardia | Italy | 27100 | |
93 | Ancona | Marche | Italy | 60126 | |
94 | Arezzo | Toscana | Italy | 52040 | |
95 | Iizuka | Fukuoka | Japan | 820-8505 | |
96 | Himeji | Hyogo | Japan | 670-0981 | |
97 | Higashiibaraki | Ibaraki | Japan | 311-3193 | |
98 | Kanazawa | Ishikawa | Japan | 920-8650 | |
99 | Takamatsu | Kagawa | Japan | 760-0018 | |
100 | Sagamihara | Kanagawa | Japan | 252-5188 | |
101 | Yokohama | Kanagawa | Japan | 236-0051 | |
102 | Yokosuka | Kanagawa | Japan | 238-8567 | |
103 | Uji | Kyoto | Japan | 611-0041 | |
104 | Naha | Okinawa | Japan | 902-8511 | |
105 | Sakai | Osaka | Japan | 599-8247 | |
106 | Takatsuki | Osaka | Japan | 569-1096 | |
107 | Komatsushima | Tokushima | Japan | 773-8502 | |
108 | Meguro-ku | Tokyo | Japan | 152-8902 | |
109 | Minato-ku | Tokyo | Japan | 106-0031 | |
110 | Fukui | Japan | 910-8526 | ||
111 | Hiroshima | Japan | 734-8530 | ||
112 | Kumamoto | Japan | 862-8505 | ||
113 | Nagasaki | Japan | 850-8555 | ||
114 | Osaka | Japan | 558-8558 | ||
115 | Tokushima | Japan | 770-8539 | ||
116 | Toyama | Japan | 930-8550 | ||
117 | Seoul | Korea, Republic of | 138-736 | ||
118 | Amsterdam | Netherlands | 1105 AZ | ||
119 | Heerenveen | Netherlands | 8441 PW | ||
120 | Leeuwarden | Netherlands | 8934 AD | ||
121 | Sneek | Netherlands | 8601 ZR | ||
122 | Bialystok | Poland | 15-276 | ||
123 | Krakow | Poland | 31-121 | ||
124 | Krakow | Poland | 31-202 | ||
125 | Lodz | Poland | 92-213 | ||
126 | Lodz | Poland | 93-513 | ||
127 | Olsztyn | Poland | 10-010 | ||
128 | Poznan | Poland | 61-848 | ||
129 | Szczecin | Poland | 70-965 | ||
130 | Almada | Portugal | 2801-951 | ||
131 | Lisboa | Portugal | 1449-005 | ||
132 | Lisboa | Portugal | 1500-650 | ||
133 | Lisboa | Portugal | 1649-035 | ||
134 | Singapore | Singapore | 119228 | ||
135 | Singapore | Singapore | 169609 | ||
136 | Singapore | Singapore | 308433 | ||
137 | Singapore | Singapore | 768828 | ||
138 | Santander | Cantabria | Spain | 39008 | |
139 | Majadahonda | Madrid | Spain | 28222 | |
140 | El Palmar | Murcia | Spain | 30120 | |
141 | Barcelona | Spain | 08003 | ||
142 | Barcelona | Spain | 08023 | ||
143 | Valencia | Spain | 46010 | ||
144 | Valencia | Spain | 46026 | ||
145 | Helsingborg | Sweden | 251 87 | ||
146 | Karlstad | Sweden | 652 30 | ||
147 | Linköping | Sweden | 581 85 | ||
148 | Stockholm | Sweden | 118 83 | ||
149 | Örebro | Sweden | 701 85 | ||
150 | Lugano | Ticino | Switzerland | 6900 | |
151 | Genève | Switzerland | 1205 | ||
152 | Kaohsiung | Taiwan | 813 | ||
153 | New Taipei City | Taiwan | 220 | ||
154 | Taipei | Taiwan | 10016 | ||
155 | Taipei | Taiwan | 11217 | ||
156 | Taoyuan | Taiwan | 333423 | ||
157 | Chesterfield | Derbyshire | United Kingdom | S44 5DX | |
158 | Stevenage | Hertfordshire | United Kingdom | SG1 4AB |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 15829
- 2013-002288-25
Study Results
Participant Flow
Recruitment Details | The study was conducted at 158 centers in 25 countries between 06 November 2013 (first subject first visit) and 16 September 2015 (last subject last visit). |
---|---|
Pre-assignment Detail | Overall, 632 subjects were enrolled, of them 477 were randomized and 475 were treated. Among the 477 subjects who were randomized, 404 subjects completed both treatment and follow-up [FU] periods. All arms in FU period were mutually exclusive, this question below is ticked No because of database validation rule constraints. |
Arm/Group Title | Placebo | BAY1021189 1.25 mg | BAY1021189 2.5 mg | BAY1021189 2.5 mg to 5 mg | BAY1021189 2.5 mg to 10 mg |
---|---|---|---|---|---|
Arm/Group Description | Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days. |
Period Title: Treatment Period | |||||
STARTED | 93 | 96 | 96 | 96 | 96 |
COMPLETED | 80 | 82 | 83 | 80 | 86 |
NOT COMPLETED | 13 | 14 | 13 | 16 | 10 |
Period Title: Treatment Period | |||||
STARTED | 89 | 95 | 95 | 88 | 94 |
COMPLETED | 87 | 86 | 90 | 80 | 89 |
NOT COMPLETED | 2 | 9 | 5 | 8 | 5 |
Baseline Characteristics
Arm/Group Title | BAY1021189 1.25 mg | Placebo | BAY1021189 2.5 mg | BAY1021189 2.5 mg to 5 mg | BAY1021189 2.5 mg to 10 mg | Total |
---|---|---|---|---|---|---|
Arm/Group Description | Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days. | Total of all reporting groups |
Overall Participants | 96 | 93 | 96 | 96 | 96 | 477 |
Age (years) [Mean (Standard Deviation) ] | ||||||
Mean (Standard Deviation) [years] |
73.8
(10)
|
73.7
(9.1)
|
72
(10.7)
|
73.9
(7.9)
|
72.5
(10.2)
|
73.2
(9.6)
|
Sex: Female, Male (Count of Participants) | ||||||
Female |
51
53.1%
|
46
49.5%
|
43
44.8%
|
43
44.8%
|
44
45.8%
|
227
47.6%
|
Male |
45
46.9%
|
47
50.5%
|
53
55.2%
|
53
55.2%
|
52
54.2%
|
250
52.4%
|
Outcome Measures
Title | Change From Baseline to Week 12 in Log-transformed N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) |
---|---|
Description | NTproBNP is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure (HF). |
Time Frame | Baseline, Week 12 (end of treatment [EOT]) |
Outcome Measure Data
Analysis Population Description |
---|
Per Protocol Set (PPS) NT-pro BNP: included all subjects randomized to treatment who had a valid measurement of NT-pro BNP at baseline and at Week 12 (Visit 5) and showed no major protocol deviations. |
Arm/Group Title | Placebo | BAY1021189 1.25 mg | BAY1021189 2.5 mg | BAY1021189 2.5 mg to 5 mg | BAY1021189 2.5 mg to 10 mg |
---|---|---|---|---|---|
Arm/Group Description | Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days. |
Measure Participants | 73 | 77 | 78 | 57 | 60 |
Mean (Standard Deviation) [log-transformed picograms per milliliter] |
-0.098
(0.778)
|
-0.047
(0.788)
|
0.071
(0.818)
|
0.057
(0.819)
|
-0.023
(0.705)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo |
---|---|---|
Comments | For the primary analysis, the three highest active treatment groups BAY1021189 (2.5mg, 2.5 to 5mg, 2.5 to 10mg) were pooled and compared to the assigned placebo treatment group with a one-sided two-sample t-test. The Hochberg procedure was used to test the two primary end points at study-wise significance level of 5%. Results are reported including 90% confidence intervals (CI) for the difference of means. The difference between the comparison groups is difference of means on the log scale. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | = 0.8991 |
Comments | ||
Method | t-test, 1 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | Log-Scale mean difference |
Estimated Value | 0.137 | |
Confidence Interval |
(2-Sided) 90% -0.04 to 0.31 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, BAY1021189 2.5 mg to 10 mg |
---|---|---|
Comments | Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | = 0.7194 |
Comments | ||
Method | t-test, 1 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | Log-Scale mean difference |
Estimated Value | 0.076 | |
Confidence Interval |
(2-Sided) 95% -0.18 to 0.33 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo, BAY1021189 2.5 mg to 5 mg |
---|---|---|
Comments | Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | = 0.8653 |
Comments | ||
Method | t-test, 1 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | Log-Scale mean difference |
Estimated Value | 0.156 | |
Confidence Interval |
(2-Sided) 95% -0.12 to 0.43 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, BAY1021189 2.5 mg |
---|---|---|
Comments | Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | = 0.9041 |
Comments | ||
Method | t-test, 1 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | Log-Scale mean difference |
Estimated Value | 0.171 | |
Confidence Interval |
(2-Sided) 95% -0.09 to 0.43 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Placebo, BAY1021189 1.25 mg |
---|---|---|
Comments | Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | = 0.6572 |
Comments | ||
Method | t-test, 1 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | Log-Scale mean difference |
Estimated Value | 0.052 | |
Confidence Interval |
(2-Sided) 95% -0.2 to 0.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline to Week 12 in Left Atrial Volume (LAV) |
---|---|
Description | Left atrial volume was measured by echocardiography. |
Time Frame | Baseline, Week 12 (EOT) |
Outcome Measure Data
Analysis Population Description |
---|
PPS Left Atrial Volume (LAV) included all subjects randomized to treatment who had a valid measurement of LAV at baseline and at Week 12 (Visit 5) and showed no major protocol deviations. |
Arm/Group Title | Placebo | BAY1021189 1.25 mg | BAY1021189 2.5 mg | BAY1021189 2.5 mg to 5 mg | BAY1021189 2.5 mg to 10 mg |
---|---|---|---|---|---|
Arm/Group Description | Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days. |
Measure Participants | 67 | 77 | 78 | 57 | 59 |
Mean (Standard Deviation) [milliliter] |
-3.361
(12.654)
|
-2.163
(7.895)
|
-2.142
(11.931)
|
-1.252
(16.139)
|
-1.654
(10.245)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo |
---|---|---|
Comments | For the primary analysis, the three highest active treatment groups (BAY1021189 2.5mg, BAY1021189 2.5 to 5mg, BAY1021189 2.5 to 10mg) were pooled and compared to the assigned placebo treatment group with a one-sided two-sample t-test. The Hochberg procedure was used to test the two primary end points at study-wise significance level of 5%. Results are reported including 90% confidence intervals (CI) for the difference of means. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | = 0.8156 |
Comments | ||
Method | t-test, 1 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Net) |
Estimated Value | 1.629 | |
Confidence Interval |
(2-Sided) 90% -1.36 to 4.62 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, BAY1021189 2.5 mg to 10 mg |
---|---|---|
Comments | Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | = 0.7945 |
Comments | ||
Method | t-test, 1 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Net) |
Estimated Value | 1.707 | |
Confidence Interval |
(2-Sided) 95% -2.39 to 5.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo, BAY1021189 2.5 mg to 5 mg |
---|---|---|
Comments | Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | = 0.7917 |
Comments | ||
Method | t-test, 1 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Net) |
Estimated Value | 2.109 | |
Confidence Interval |
(2-Sided) 95% -3.01 to 7.23 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, BAY1021189 2.5 mg |
---|---|---|
Comments | Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | = 0.7241 |
Comments | ||
Method | t-test, 1 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Net) |
Estimated Value | 1.219 | |
Confidence Interval |
(2-Sided) 95% -2.82 to 5.26 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Placebo, BAY1021189 1.25 mg |
---|---|---|
Comments | Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | = 0.7546 |
Comments | ||
Method | t-test, 1 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Net) |
Estimated Value | 1.198 | |
Confidence Interval |
(2-Sided) 95% -2.23 to 4.63 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline to Week 12 Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
---|---|
Description | Blood pressure was measured after at least 10 minutes resting in a sitting position (3 measurements taken approximately 2 minutes apart).The changes in blood pressure were recorded and the mean of the three measurements was analyzed. |
Time Frame | Baseline, Week 12 (EOT) |
Outcome Measure Data
Analysis Population Description |
---|
Safety Analysis Set (SAF) with evaluable subjects for this endpoint. |
Arm/Group Title | Placebo | BAY1021189 1.25 mg | BAY1021189 2.5 mg | BAY1021189 2.5 mg to 5 mg | BAY1021189 2.5 mg to 10 mg |
---|---|---|---|---|---|
Arm/Group Description | Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days. |
Measure Participants | 80 | 82 | 83 | 61 | 61 |
Change in SBP |
1.458
(18.865)
|
0.703
(16.993)
|
-1.819
(19.438)
|
-1.486
(17.179)
|
-0.913
(15.498)
|
Change in DBP |
1.887
(11.435)
|
0.911
(10.037)
|
-2.173
(11.249)
|
-1.142
(11.4)
|
-0.629
(10.271)
|
Title | Change From Baseline to Week 12 in Heart Rate |
---|---|
Description | Heart rate was measured after 10 minutes resting in a sitting position (3 measurements taken approximatly 2 minutes apart). The changes in heart rate were recorded and the mean of the three measurements was analyzed. |
Time Frame | Baseline, Week 12 (EOT) |
Outcome Measure Data
Analysis Population Description |
---|
Safety Analysis Set (SAF) with evaluable subjects for this endpoint. |
Arm/Group Title | Placebo | BAY1021189 1.25 mg | BAY1021189 2.5 mg | BAY1021189 2.5 mg to 5 mg | BAY1021189 2.5 mg to 10 mg |
---|---|---|---|---|---|
Arm/Group Description | Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days. |
Measure Participants | 80 | 82 | 83 | 61 | 61 |
Mean (Standard Deviation) [beats per minute] |
3.287
(13.582)
|
1.776
(11.42)
|
-0.373
(9.845)
|
1.055
(13.331)
|
-2.623
(9.639)
|
Title | Number of Subjects With Clinical Events (Heart Failure Hospitalization and Cardio-vascular [CV] Mortality) |
---|---|
Description | Clinical events (heart failure and mortality) were analyzed as CV death, and HF hospitalization at specified time points. |
Time Frame | Baseline up to Week 16 including 12 week treatment period and 4 week follow-up period |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set (FAS) included all subjects who were randomized to treatment. |
Arm/Group Title | Placebo | BAY1021189 1.25 mg | BAY1021189 2.5 mg | BAY1021189 2.5 mg to 5 mg | BAY1021189 2.5 mg to 10 mg |
---|---|---|---|---|---|
Arm/Group Description | Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days. |
Measure Participants | 93 | 96 | 96 | 96 | 96 |
HF hospitalizations |
8
8.3%
|
6
6.5%
|
11
11.5%
|
8
8.3%
|
5
5.2%
|
CV Mortality |
1
1%
|
0
0%
|
0
0%
|
5
5.2%
|
1
1%
|
Adverse Events
Time Frame | Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||||||
Arm/Group Title | Placebo | BAY1021189 1.25 mg | BAY1021189 2.5 mg | BAY1021189 From 2.5 to 5 mg | BAY1021189 From 2.5 to 10 mg | |||||
Arm/Group Description | Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28. | Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days. | |||||
All Cause Mortality |
||||||||||
Placebo | BAY1021189 1.25 mg | BAY1021189 2.5 mg | BAY1021189 From 2.5 to 5 mg | BAY1021189 From 2.5 to 10 mg | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/93 (1.1%) | 0/96 (0%) | 1/95 (1.1%) | 7/95 (7.4%) | 2/96 (2.1%) | |||||
Serious Adverse Events |
||||||||||
Placebo | BAY1021189 1.25 mg | BAY1021189 2.5 mg | BAY1021189 From 2.5 to 5 mg | BAY1021189 From 2.5 to 10 mg | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 20/93 (21.5%) | 20/96 (20.8%) | 24/95 (25.3%) | 18/95 (18.9%) | 21/96 (21.9%) | |||||
Blood and lymphatic system disorders | ||||||||||
Anaemia | 2/93 (2.2%) | 3 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Anaemia of chronic disease | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Cardiac disorders | ||||||||||
Angina unstable | 1/93 (1.1%) | 1 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Atrial fibrillation | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 2/95 (2.1%) | 3 | 1/95 (1.1%) | 1 | 1/96 (1%) | 2 |
Cardiac arrest | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Cardiac failure | 6/93 (6.5%) | 6 | 4/96 (4.2%) | 4 | 7/95 (7.4%) | 12 | 5/95 (5.3%) | 8 | 2/96 (2.1%) | 2 |
Cardiac failure acute | 1/93 (1.1%) | 1 | 1/96 (1%) | 1 | 3/95 (3.2%) | 3 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Cardiac failure chronic | 2/93 (2.2%) | 3 | 4/96 (4.2%) | 4 | 3/95 (3.2%) | 3 | 2/95 (2.1%) | 2 | 4/96 (4.2%) | 5 |
Cardiac failure congestive | 2/93 (2.2%) | 2 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 3/95 (3.2%) | 3 | 0/96 (0%) | 0 |
Cardiogenic shock | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 1/95 (1.1%) | 1 | 0/96 (0%) | 0 |
Myocardial infarction | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Right ventricular failure | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 1/95 (1.1%) | 1 | 0/96 (0%) | 0 |
Tachyarrhythmia | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Acute coronary syndrome | 0/93 (0%) | 0 | 2/96 (2.1%) | 2 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Ear and labyrinth disorders | ||||||||||
Vertigo | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Eye disorders | ||||||||||
Vitreous haemorrhage | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Gastrointestinal disorders | ||||||||||
Diarrhoea | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 1/95 (1.1%) | 1 | 1/96 (1%) | 1 |
Gastrointestinal haemorrhage | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Large intestine polyp | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Intestinal haemorrhage | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
General disorders | ||||||||||
Chest pain | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 1/95 (1.1%) | 1 | 0/96 (0%) | 0 |
Pain | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Pyrexia | 1/93 (1.1%) | 2 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Sudden death | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 1/95 (1.1%) | 1 | 0/96 (0%) | 0 |
Hepatobiliary disorders | ||||||||||
Cholelithiasis | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Jaundice cholestatic | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Infections and infestations | ||||||||||
Carbuncle | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Diabetic gangrene | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Erysipelas | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 1/95 (1.1%) | 1 | 0/96 (0%) | 0 |
Gangrene | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Gastroenteritis | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Hepatitis C | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Osteomyelitis | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Pneumonia | 1/93 (1.1%) | 2 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 3/96 (3.1%) | 3 |
Respiratory syncytial virus bronchiolitis | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Urinary tract infection | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Urosepsis | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Urinary tract infection bacterial | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Enterococcal sepsis | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Chlamydial infection | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 1/95 (1.1%) | 1 | 0/96 (0%) | 0 |
Respiratory tract infection | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Injury, poisoning and procedural complications | ||||||||||
Femoral neck fracture | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Radius fracture | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Ulna fracture | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Vascular pseudoaneurysm | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Contusion | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Post procedural haematoma | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Investigations | ||||||||||
Coagulation time prolonged | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Intraocular pressure increased | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||
Diabetes mellitus | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Failure to thrive | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Hypoglycaemia | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||
Osteochondrosis | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
Non-Hodgkin's lymphoma | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Gastrointestinal stromal tumour | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Nervous system disorders | ||||||||||
Carotid artery stenosis | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Cerebral haemorrhage | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Presyncope | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 2 |
Syncope | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 2 |
Cervicogenic headache | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 1/95 (1.1%) | 1 | 0/96 (0%) | 0 |
Renal and urinary disorders | ||||||||||
Renal impairment | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Acute kidney injury | 2/93 (2.2%) | 2 | 1/96 (1%) | 1 | 1/95 (1.1%) | 1 | 4/95 (4.2%) | 4 | 3/96 (3.1%) | 3 |
Respiratory, thoracic and mediastinal disorders | ||||||||||
Acute pulmonary oedema | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Chronic obstructive pulmonary disease | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 1/95 (1.1%) | 1 | 1/95 (1.1%) | 1 | 2/96 (2.1%) | 2 |
Dyspnoea | 1/93 (1.1%) | 1 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Epistaxis | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 1/95 (1.1%) | 1 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Pleural effusion | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 1/95 (1.1%) | 1 | 0/96 (0%) | 0 |
Pulmonary hypertension | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Respiratory failure | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 1/95 (1.1%) | 1 | 0/96 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||
Diabetic foot | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Surgical and medical procedures | ||||||||||
Eyelid operation | 0/93 (0%) | 0 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Vascular disorders | ||||||||||
Circulatory collapse | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 1/95 (1.1%) | 1 | 0/96 (0%) | 0 |
Hypotension | 0/93 (0%) | 0 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 1/96 (1%) | 1 |
Orthostatic hypotension | 1/93 (1.1%) | 1 | 0/96 (0%) | 0 | 0/95 (0%) | 0 | 0/95 (0%) | 0 | 0/96 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||
Placebo | BAY1021189 1.25 mg | BAY1021189 2.5 mg | BAY1021189 From 2.5 to 5 mg | BAY1021189 From 2.5 to 10 mg | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 21/93 (22.6%) | 33/96 (34.4%) | 40/95 (42.1%) | 38/95 (40%) | 33/96 (34.4%) | |||||
Cardiac disorders | ||||||||||
Cardiac failure | 5/93 (5.4%) | 5 | 1/96 (1%) | 1 | 3/95 (3.2%) | 4 | 3/95 (3.2%) | 3 | 2/96 (2.1%) | 2 |
Gastrointestinal disorders | ||||||||||
Abdominal pain upper | 1/93 (1.1%) | 1 | 1/96 (1%) | 1 | 5/95 (5.3%) | 5 | 2/95 (2.1%) | 2 | 0/96 (0%) | 0 |
Nausea | 2/93 (2.2%) | 2 | 2/96 (2.1%) | 2 | 4/95 (4.2%) | 5 | 5/95 (5.3%) | 5 | 4/96 (4.2%) | 5 |
General disorders | ||||||||||
Fatigue | 2/93 (2.2%) | 3 | 2/96 (2.1%) | 2 | 3/95 (3.2%) | 3 | 6/95 (6.3%) | 6 | 4/96 (4.2%) | 4 |
Oedema peripheral | 2/93 (2.2%) | 3 | 3/96 (3.1%) | 4 | 2/95 (2.1%) | 3 | 6/95 (6.3%) | 7 | 1/96 (1%) | 1 |
Infections and infestations | ||||||||||
Bronchitis | 1/93 (1.1%) | 1 | 1/96 (1%) | 1 | 2/95 (2.1%) | 2 | 4/95 (4.2%) | 4 | 6/96 (6.3%) | 6 |
Nasopharyngitis | 3/93 (3.2%) | 3 | 4/96 (4.2%) | 4 | 6/95 (6.3%) | 8 | 1/95 (1.1%) | 1 | 5/96 (5.2%) | 5 |
Metabolism and nutrition disorders | ||||||||||
Hyperkalaemia | 0/93 (0%) | 0 | 6/96 (6.3%) | 6 | 2/95 (2.1%) | 2 | 3/95 (3.2%) | 3 | 3/96 (3.1%) | 3 |
Nervous system disorders | ||||||||||
Dizziness | 3/93 (3.2%) | 3 | 2/96 (2.1%) | 4 | 10/95 (10.5%) | 11 | 6/95 (6.3%) | 6 | 7/96 (7.3%) | 7 |
Headache | 1/93 (1.1%) | 1 | 1/96 (1%) | 1 | 6/95 (6.3%) | 6 | 4/95 (4.2%) | 4 | 4/96 (4.2%) | 4 |
Renal and urinary disorders | ||||||||||
Renal failure | 2/93 (2.2%) | 3 | 5/96 (5.2%) | 5 | 0/95 (0%) | 0 | 1/95 (1.1%) | 1 | 0/96 (0%) | 0 |
Acute kidney injury | 1/93 (1.1%) | 1 | 1/96 (1%) | 1 | 0/95 (0%) | 0 | 5/95 (5.3%) | 5 | 1/96 (1%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||||||||
Cough | 1/93 (1.1%) | 1 | 5/96 (5.2%) | 5 | 6/95 (6.3%) | 6 | 2/95 (2.1%) | 2 | 2/96 (2.1%) | 2 |
Dyspnoea | 3/93 (3.2%) | 3 | 6/96 (6.3%) | 7 | 9/95 (9.5%) | 10 | 5/95 (5.3%) | 6 | 3/96 (3.1%) | 3 |
Vascular disorders | ||||||||||
Hypotension | 1/93 (1.1%) | 1 | 4/96 (4.2%) | 4 | 4/95 (4.2%) | 6 | 5/95 (5.3%) | 5 | 2/96 (2.1%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title | Therapeutic Area Head |
---|---|
Organization | Bayer AG |
Phone | |
clinical-trials-contact@bayer.com |
- 15829
- 2013-002288-25