REPLACE: Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy
Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT02891850
Collaborator
(none)
225
81
2
37.7
2.8
0.1
Study Details
Study Description
Brief Summary
To demonstrate the effectiveness of riociguat as replacement of phosphodiesterase-5 inhibitors (PDE-5i) therapy in pulmonary arterial hypertension (PAH) patients
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Data from a previous single arm study (RESPITE) indicate that transition from PDE5i to riociguat may be feasible, safe and beneficial in patients not adequately responding to PDE5i.
REPLACE is a randomized controlled study to confirm the potential clinical benefit of transition from PDE5i to riociguat. Satisfactory clinical response in patients who are on a stable dose of phosphodiesterase-5inhibitors (PDE-5i) with or without endothelin receptor antagonist (ERA), but not at treatment goal will be compared between one group of patients randomized to maintain current treatment and another group where the PDE5i is replaced by riociguat.
Study Design
Study Type:
Interventional
Actual Enrollment
:
225 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Prospective, Randomized, International, Multicenter, Double-arm, Controlled, Open-label Study of Riociguat in Patients With Pulmonary Arterial Hypertension (PAH) Who Are on a Stable Dose of Phosphodiesterase-5 Inhibitors (PDE-5i) With or Without Endothelin Receptor Antagonist (ERA), But Not at Treatment Goal
Actual Study Start Date
:
Jan 11, 2017
Actual Primary Completion Date
:
Jan 29, 2020
Actual Study Completion Date
:
Mar 3, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Riociguat PDE5i treatment will be stopped and riociguat treatment initiated following a defined washout period with a starting dose of 1 mg riociguat TID followed by an 8 weeks dose adjustment phase according to the approved riociguat dose adjustment scheme. |
Drug: Riociguat (Adempas, BAY63-2521)
Film-coated tablets will be used in this study at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg. Tablets will be administered orally.The starting dose is 1 mg TID; the intervals between drug intakes should be 6 to 8 hours. The dosage should be increased by 0.5 mg increments in 2 week intervals to 1.5 mg, 2.0 mg, and 2.5 mg TID (maximal total daily dose).
|
| Active Comparator: PDE-5i Patients will continue to receive PDE5i treatment as well as other standard of care treatments at the discretion of the investigator up to Week 24. Patients in the experimental and active comparator treatment arms follow the same visit schedule. |
Drug: Sildenafil
Patients randomized to the control arm will continue to receive stable doses of tadalafil (daily dose 20 to 40 mg) or sildenafil (daily dose at least 60 mg) as well as other supportive treatments at the discretion of the investigator.
Drug: Tadalafil
Patients randomized to the control arm will continue to receive stable doses of tadalafil (daily dose 20 to 40 mg) or sildenafil (daily dose at least 60 mg) as well as other supportive treatments at the discretion of the investigator.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Satisfactory Clinical Response at Week 24 [At Week 24]
The treatment is assessed as efficient (participants with satisfactory clinical response) in case at least 2 out of the following 3 criteria were fulfilled 6 Minute Walking Distance increase by ≥ 10% or ≥ 30 m from baseline to Week 24 World Health Organization Functional Class (WHO FC) I or II at Week 24 N-terminal pro-brain natriuretic peptide (NT-proBNP) reduction ≥ 30% from baseline to Week 24 (NT-proBNP ratio Week 24/baseline ≤ 0.7) and in absence of the defined criteria of clinical worsening
Secondary Outcome Measures
- Change in 6 Minute Walking Distance (6MWD) With Last Observation Carried Forward From Baseline to 24 Weeks [From baseline and up to 24 weeks]
Six-minute walk distance (6MWD) was conducted to test the physical limitations of the participant by assessing the participant's exercise capacity. The distance walked by the participant in 6 minutes was measured.
- Change in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) With Last Observation Carried Forward at Week 24 [From baseline and up to 24 weeks]
N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure.
- Change in World Health Organization Functional Class (WHO FC) With Last Observation Carried Forward From Baseline to Week 24 [From baseline and up to 24 weeks]
The participant's functional class was determined by using the WHO classification. Possible classes range from I (patients with pulmonary hypertension (PH) but without resulting limitation of physical activity) to IV (patients with PH with inability to carry out any physical activity without symptoms).
- Number of Participants With Adjudicated Clinical Worsening at Week 24 [Up to 24 weeks]
Clinical worsening was defined as death of any cause, hospitalization due to worsening pulmonary arterial hypertension (PAH) (adjudicated) or disease progression (adjudicated).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male and female patients aged 18 to 75 years.
-
Patients with symptomatic PAH with a pulmonary vascular resistance (PVR) > 400 dynseccm-5, mean pulmonary artery pressure ≥ 25 mmHg, and pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg as assessed by the most recent right heart catheterization (RHC) from medical history prior to screening to confirm the diagnosis. Alternatively, PCWP can be replaced by left ventricular end-diastolic pressure (≤ 15 mmHg). PAH of the following types:
-
Idiopathic
-
Hereditary
-
Drug and toxin induced PAH
-
Associated with PAH due to:
-
Connective tissue disease (CTD)
-
Congenital heart disease, but only if the patient underwent surgical repair more than one year before enrolment
-
Portal hypertension with liver cirrhosis (Note: patients with clinical relevant hepatic dysfunction are excluded; see exclusions related to disorders in organ function)
-
Patients who are on stable doses of a PDE-5i and ERA combination therapy or on stable PDE-5i monotherapy 6 weeks prior to and at randomization but not at treatment goal (tadalafil 20 to 40 mg once daily or sildenafil at least 60 mg daily dose).
-
WHO FC III at screening and at randomization.
-
6MWD test between 165 m and 440 m at screening and at randomization.
-
Stable dose of diuretics, if used, for at least 30 days prior to and at randomization.
-
Patients who are able to understand and follow instructions and who are able to participate in the study for the entire study.
-
Women of childbearing potential must agree to use adequate contraception when sexually active. Adequate contraception is defined as any combination of at least 2 effective methods of birth control, of which at least 1 is a physical barrier (e.g. condom with hormonal contraception like implants or combined oral contraceptives, condom with intrauterine devices). This applies beginning with signing of the informed consent form until 30 (+5) days after the last administration of study drug.
-
Patients 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:
-
Participation in another interventional clinical study within 30 days prior to screening.
-
All types of PH (including PH-IIP) except subtypes of Dana Point Group I specified in the inclusion criteria.
-
Previous treatment with riociguat.
-
Pregnant women (i.e., positive serum ß-human-chorionic-gonadotropin test or other signs of pregnancy), or breast feeding women, or women with childbearing potential not using a combination of 2 effective contraception methods (as laid out in inclusion criterion) throughout the study.
-
Patients with a medical disorder, condition, or history of such that would impair the patient's ability to participate or complete this study, in the opinion of the investigator.
-
Relevant obstructive and restrictive or other lung diseases.
-
Patients with underlying medical disorders with an anticipated life expectancy below 2 years (e.g., active cancer disease with localized and/or metastasized tumor mass).
-
Cardiovascular exclusion criteria like left ventricular disease, coronary heart disease or stroke within previous 3 months.
-
Patients with hypersensitivity to the investigational drug or any of the excipients.
-
Patients unable to perform a valid 6MWD test (e.g., orthopedic disease, peripheral artery occlusive disease, which affects the patient's ability to walk). Note: Patients, who require walking aids, may be included if in the opinion of the investigator the walking distance is not impaired. Patients with a variance of more than 15% between the screening and the randomization (i.e., baseline) 6MWD test.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Phoenix | Arizona | United States | 85012 | |
| 2 | Tucson | Arizona | United States | 85724 | |
| 3 | Sacramento | California | United States | 95817 | |
| 4 | Orlando | Florida | United States | 32803 | |
| 5 | Weston | Florida | United States | 33331 | |
| 6 | Kansas City | Kansas | United States | 66103 | |
| 7 | Louisville | Kentucky | United States | 40202 | |
| 8 | Detroit | Michigan | United States | 48202 | |
| 9 | Troy | Michigan | United States | 48085 | |
| 10 | Newark | New Jersey | United States | 07112 | |
| 11 | Mineola | New York | United States | 11501 | |
| 12 | New York | New York | United States | 10003 | |
| 13 | Rochester | New York | United States | 14623 | |
| 14 | Cleveland | Ohio | United States | 44195 | |
| 15 | Nashville | Tennessee | United States | 37232 | |
| 16 | Dallas | Texas | United States | 75390 | |
| 17 | Richmond | Virginia | United States | 23225 | |
| 18 | Graz | Austria | 8036 | ||
| 19 | Leuven | Belgium | 3000 | ||
| 20 | Belo Horizonte | Minas Gerais | Brazil | 30130-100 | |
| 21 | Belo Horizonte | Minas Gerais | Brazil | 30441-070 | |
| 22 | Porto Alegre | Rio Grande Do Sul | Brazil | 90050-170 | |
| 23 | Blumenal | Santa Catarina | Brazil | 89030-101 | |
| 24 | Sao Paulo | Brazil | 04023-061 | ||
| 25 | Sao Paulo | Brazil | 05403-000 | ||
| 26 | Montreal | Quebec | Canada | H3T 1E2 | |
| 27 | Praha 2 | Czechia | 12808 | ||
| 28 | Praha 4 | Czechia | 140 21 | ||
| 29 | Aarhus N | Denmark | 8200 | ||
| 30 | Le Kremlin-Bicêtre | France | 94270 | ||
| 31 | Rouen | France | 76031 | ||
| 32 | Heidelberg | Baden-Württemberg | Germany | 69126 | |
| 33 | München | Bayern | Germany | 80639 | |
| 34 | München | Bayern | Germany | 81377 | |
| 35 | Würzburg | Bayern | Germany | 97074 | |
| 36 | Hannover | Niedersachsen | Germany | 30625 | |
| 37 | Köln | Nordrhein-Westfalen | Germany | 50937 | |
| 38 | Homburg | Saarland | Germany | 66421 | |
| 39 | Dresden | Sachsen | Germany | 01307 | |
| 40 | Leipzig | Sachsen | Germany | 04103 | |
| 41 | Lübeck | Schleswig-Holstein | Germany | 23538 | |
| 42 | Berlin | Germany | 14050 | ||
| 43 | Gießen | Germany | 35390 | ||
| 44 | Hamburg | Germany | 20246 | ||
| 45 | Chaidari | Greece | 124 62 | ||
| 46 | Thessaloniki | Greece | 546 36 | ||
| 47 | Thessaloniki | Greece | 57010 | ||
| 48 | Napoli | Campania | Italy | 80131 | |
| 49 | Roma | Lazio | Italy | 00161 | |
| 50 | Pavia | Lombardia | Italy | 27100 | |
| 51 | Palermo | Sicilia | Italy | 90127 | |
| 52 | Nagoya | Aichi | Japan | 467-8602 | |
| 53 | Sendai | Miyagi | Japan | 980-8574 | |
| 54 | Bunkyo-ku | Tokyo | Japan | 113-8655 | |
| 55 | Seoul | Korea, Republic of | 03722 | ||
| 56 | Seoul | Korea, Republic of | 110-744 | ||
| 57 | Seoul | Korea, Republic of | 135-710 | ||
| 58 | Seoul | Korea, Republic of | 138-736 | ||
| 59 | Culiacan | Sinaloa | Mexico | 80020 | |
| 60 | Mexico D.F. | Mexico | 14080 | ||
| 61 | Amsterdam | Netherlands | 1081 HV | ||
| 62 | Nijmegen | Netherlands | 6500HB | ||
| 63 | Wroclaw | Poland | 51-124 | ||
| 64 | Almada | Lisboa | Portugal | 2801-951 | |
| 65 | Coimbra | Portugal | 3000-075 | ||
| 66 | Lisboa | Portugal | 1649-035 | ||
| 67 | Las Palmas de Gran Canaria | Las Palmas | Spain | 35020 | |
| 68 | Barcelona | Spain | 08035 | ||
| 69 | Barcelona | Spain | 08036 | ||
| 70 | Toledo | Spain | 45004 | ||
| 71 | Kaoshiung | Taiwan | 81346 | ||
| 72 | Tainan | Taiwan | 704 | ||
| 73 | Taipei | Taiwan | 10016 | ||
| 74 | Ankara | Turkey | 06100 | ||
| 75 | Istanbul | Turkey | 34-300 | ||
| 76 | Istanbul | Turkey | 34093 | ||
| 77 | Izmir | Turkey | 34098 | ||
| 78 | Clydebank | West Dunbartonshire | United Kingdom | G81 4DY | |
| 79 | London | United Kingdom | NW3 2QG | ||
| 80 | London | United Kingdom | SW3 6NP | ||
| 81 | Sheffield | United Kingdom | S10 2JF |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
More Information
Additional Information:
- Click here to find results for studies related to Bayer products.
- Click here to find information about studies related to Bayer Healthcare products conducted in Europe
Publications
None provided.Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT02891850
Other Study ID Numbers:
- 18588
- 2016-001067-36
First Posted:
Sep 8, 2016
Last Update Posted:
Feb 26, 2021
Last Verified:
Jan 1, 2021
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study was conducted at multiple centers in 21 countries between 11-JAN-2017 (first participant first visit) and 03-MAR-2020 (last participant last visit). |
|---|---|
| Pre-assignment Detail | 293 participants were screened in this study. Of these, 67 participants did not enter the treatment period (60 screening failures; 2 withdraw during screening; 2 withdraw following physician decision; 3 withdraw due to other reasons). 226 participants were randomized, of which 1 participant withdraw before treated. |
| Arm/Group Title | Riociguat | PDE-5i |
|---|---|---|
| Arm/Group Description | Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks. | Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator. |
| Period Title: Overall Study | ||
| STARTED | 111 | 114 |
| COMPLETED | 104 | 107 |
| NOT COMPLETED | 7 | 7 |
Baseline Characteristics
| Arm/Group Title | Riociguat | PDE-5i | Total |
|---|---|---|---|
| Arm/Group Description | Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks. | Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator. | Total of all reporting groups |
| Overall Participants | 111 | 114 | 225 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
49.4
(16.16)
|
49.2
(15.64)
|
49.3
(15.86)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
82
73.9%
|
95
83.3%
|
177
78.7%
|
| Male |
29
26.1%
|
19
16.7%
|
48
21.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
32
28.8%
|
31
27.2%
|
63
28%
|
| Not Hispanic or Latino |
75
67.6%
|
80
70.2%
|
155
68.9%
|
| Unknown or Not Reported |
4
3.6%
|
3
2.6%
|
7
3.1%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
1
0.9%
|
0
0%
|
1
0.4%
|
| Asian |
17
15.3%
|
19
16.7%
|
36
16%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
4
3.6%
|
5
4.4%
|
9
4%
|
| White |
86
77.5%
|
89
78.1%
|
175
77.8%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
3
2.7%
|
1
0.9%
|
4
1.8%
|
Outcome Measures
| Title | Number of Participants With Satisfactory Clinical Response at Week 24 |
|---|---|
| Description | The treatment is assessed as efficient (participants with satisfactory clinical response) in case at least 2 out of the following 3 criteria were fulfilled 6 Minute Walking Distance increase by ≥ 10% or ≥ 30 m from baseline to Week 24 World Health Organization Functional Class (WHO FC) I or II at Week 24 N-terminal pro-brain natriuretic peptide (NT-proBNP) reduction ≥ 30% from baseline to Week 24 (NT-proBNP ratio Week 24/baseline ≤ 0.7) and in absence of the defined criteria of clinical worsening |
| Time Frame | At Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) with evaluable participants |
| Arm/Group Title | Riociguat | PDE-5i |
|---|---|---|
| Arm/Group Description | Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks. | Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator. |
| Measure Participants | 111 | 113 |
| With satisfactory clinical response |
45
40.5%
|
23
20.2%
|
| Without satisfactory clinical response |
66
59.5%
|
90
78.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Riociguat, PDE-5i |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | The hypothesis was that there was no difference in the satisfactory clinical response rates in terms of odds ratio (OR) when treated with riociguat compared with participants who remained on their previous therapy. | |
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | ||
| Method | Mantel Haenszel | |
| Comments | Stratified by PAH category at baseline | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.78 | |
| Confidence Interval |
(2-Sided) 95% 1.526 to 5.060 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in 6 Minute Walking Distance (6MWD) With Last Observation Carried Forward From Baseline to 24 Weeks |
|---|---|
| Description | Six-minute walk distance (6MWD) was conducted to test the physical limitations of the participant by assessing the participant's exercise capacity. The distance walked by the participant in 6 minutes was measured. |
| Time Frame | From baseline and up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) with evaluable participants |
| Arm/Group Title | Riociguat | PDE-5i |
|---|---|---|
| Arm/Group Description | Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks. | Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator. |
| Measure Participants | 111 | 113 |
| Mean (Standard Deviation) [meters (m)] |
36.448
(65.9748)
|
13.884
(67.1552)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Riociguat, PDE-5i |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | The hypothesis was that there was no difference in the change of 6MWD in terms of mean difference when treated with riociguat compared with participants who remained on their previous therapy. | |
| Statistical Test of Hypothesis | p-Value | 0.0542 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | Stratified by PAH category at baseline | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 22.56 | |
| Confidence Interval |
(2-Sided) 95% 5.03 to 40.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) With Last Observation Carried Forward at Week 24 |
|---|---|
| Description | N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure. |
| Time Frame | From baseline and up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) with evaluable participants |
| Arm/Group Title | Riociguat | PDE-5i |
|---|---|---|
| Arm/Group Description | Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks. | Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator. |
| Measure Participants | 108 | 113 |
| Mean (Standard Deviation) [picograms per milliliter (pg/mL)] |
-88.234
(533.9179)
|
81.414
(1267.6142)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Riociguat, PDE-5i |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | The hypothesis was that there was no difference in the change of NT-proBNP in terms of mean difference when treated with riociguat compared with participants who remained on their previous therapy. | |
| Statistical Test of Hypothesis | p-Value | 0.1067 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | Stratified by PAH category at baseline | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -169.65 | |
| Confidence Interval |
(2-Sided) 95% -426.18 to 86.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in World Health Organization Functional Class (WHO FC) With Last Observation Carried Forward From Baseline to Week 24 |
|---|---|
| Description | The participant's functional class was determined by using the WHO classification. Possible classes range from I (patients with pulmonary hypertension (PH) but without resulting limitation of physical activity) to IV (patients with PH with inability to carry out any physical activity without symptoms). |
| Time Frame | From baseline and up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) with evaluable participants |
| Arm/Group Title | Riociguat | PDE-5i |
|---|---|---|
| Arm/Group Description | Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks. | Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator. |
| Measure Participants | 111 | 113 |
| Mean (Standard Deviation) [class] |
-0.5
(0.58)
|
-0.2
(0.62)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Riociguat, PDE-5i |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | The hypothesis was that there was no difference in the change from baseline in WHO FC in terms of mean difference when treated with riociguat compared with participants who remained on their previous therapy. | |
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | Stratified by PAH category at baseline | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.26 | |
| Confidence Interval |
(2-Sided) 95% -0.42 to -0.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Adjudicated Clinical Worsening at Week 24 |
|---|---|
| Description | Clinical worsening was defined as death of any cause, hospitalization due to worsening pulmonary arterial hypertension (PAH) (adjudicated) or disease progression (adjudicated). |
| Time Frame | Up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) with evaluable participants |
| Arm/Group Title | Riociguat | PDE-5i |
|---|---|---|
| Arm/Group Description | Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks. | Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator. |
| Measure Participants | 111 | 113 |
| Count of Participants [Participants] |
1
0.9%
|
10
8.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Riociguat, PDE-5i |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | The hypothesis was that there was no difference in the clinical worsening rates in terms of odds ratio (OR) when treated with riociguat compared with participants who remained on their previous therapy. | |
| Statistical Test of Hypothesis | p-Value | 0.0047 |
| Comments | ||
| Method | Mantel Haenszel | |
| Comments | Stratified by PAH category at baseline | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.10 | |
| Confidence Interval |
(2-Sided) 95% 0.013 to 0.725 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Riociguat | PDE-5i | ||
| Arm/Group Description | Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks. | Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator. | ||
All Cause Mortality |
||||
| Riociguat | PDE-5i | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/111 (0%) | 4/114 (3.5%) | ||
Serious Adverse Events |
||||
| Riociguat | PDE-5i | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/111 (7.2%) | 19/114 (16.7%) | ||
| Blood and lymphatic system disorders | ||||
| Iron deficiency anaemia | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Cardiac disorders | ||||
| Arrhythmia supraventricular | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Atrial fibrillation | 0/111 (0%) | 0 | 1/114 (0.9%) | 2 |
| Cardiac failure | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Right ventricular failure | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Gastrointestinal haemorrhage | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Small intestinal obstruction | 1/111 (0.9%) | 3 | 0/114 (0%) | 0 |
| General disorders | ||||
| Chest pain | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Infections and infestations | ||||
| Gastroenteritis | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Pneumonia | 0/111 (0%) | 0 | 2/114 (1.8%) | 2 |
| Tracheobronchitis | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Viral infection | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Respiratory tract infection | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Investigations | ||||
| Pulmonary arterial pressure increased | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Osteonecrosis | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Nervous system disorders | ||||
| Epilepsy | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Syncope | 1/111 (0.9%) | 1 | 1/114 (0.9%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Dyspnoea exertional | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Epistaxis | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Pulmonary hypertension | 0/111 (0%) | 0 | 2/114 (1.8%) | 2 |
| Pulmonary arterial hypertension | 0/111 (0%) | 0 | 2/114 (1.8%) | 3 |
| Surgical and medical procedures | ||||
| Drug therapy enhancement | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Vascular disorders | ||||
| Hypotension | 2/111 (1.8%) | 3 | 0/114 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Riociguat | PDE-5i | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 77/111 (69.4%) | 72/114 (63.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Anaemia megaloblastic | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Iron deficiency anaemia | 2/111 (1.8%) | 2 | 0/114 (0%) | 0 |
| Leukopenia | 0/111 (0%) | 0 | 2/114 (1.8%) | 2 |
| Lymphopenia | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Neutropenia | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Cardiac disorders | ||||
| Arrhythmia | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Atrial fibrillation | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Cardiac failure chronic | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Palpitations | 3/111 (2.7%) | 4 | 4/114 (3.5%) | 4 |
| Sinus tachycardia | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Tachycardia | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Ventricular extrasystoles | 0/111 (0%) | 0 | 2/114 (1.8%) | 2 |
| Ear and labyrinth disorders | ||||
| Vertigo | 2/111 (1.8%) | 3 | 0/114 (0%) | 0 |
| Eye disorders | ||||
| Astigmatism | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Cataract | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Eye irritation | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Glaucoma | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Retinal disorder | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Ocular discomfort | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 3/111 (2.7%) | 3 | 0/114 (0%) | 0 |
| Abdominal distension | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Abdominal pain | 3/111 (2.7%) | 3 | 0/114 (0%) | 0 |
| Abdominal pain lower | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Abdominal pain upper | 3/111 (2.7%) | 3 | 1/114 (0.9%) | 1 |
| Constipation | 4/111 (3.6%) | 5 | 0/114 (0%) | 0 |
| Diarrhoea | 6/111 (5.4%) | 6 | 3/114 (2.6%) | 3 |
| Dyspepsia | 10/111 (9%) | 10 | 0/114 (0%) | 0 |
| Flatulence | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Gastritis | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Gastrooesophageal reflux disease | 8/111 (7.2%) | 10 | 1/114 (0.9%) | 1 |
| Gingival hypertrophy | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Irritable bowel syndrome | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Nausea | 5/111 (4.5%) | 6 | 3/114 (2.6%) | 3 |
| Toothache | 0/111 (0%) | 0 | 2/114 (1.8%) | 2 |
| Vomiting | 3/111 (2.7%) | 3 | 0/114 (0%) | 0 |
| Gastrointestinal hypermotility | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Reflux gastritis | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| General disorders | ||||
| Asthenia | 0/111 (0%) | 0 | 2/114 (1.8%) | 2 |
| Chest discomfort | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Chest pain | 5/111 (4.5%) | 8 | 5/114 (4.4%) | 5 |
| Drug ineffective | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Fatigue | 6/111 (5.4%) | 7 | 2/114 (1.8%) | 2 |
| Malaise | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Oedema | 2/111 (1.8%) | 2 | 2/114 (1.8%) | 2 |
| Oedema mucosal | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Oedema peripheral | 3/111 (2.7%) | 4 | 4/114 (3.5%) | 4 |
| Pyrexia | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Peripheral swelling | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Hepatobiliary disorders | ||||
| Hepatomegaly | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Immune system disorders | ||||
| Drug hypersensitivity | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Hypersensitivity | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Infections and infestations | ||||
| Acute sinusitis | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Body tinea | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Bronchitis | 1/111 (0.9%) | 1 | 2/114 (1.8%) | 2 |
| Conjunctivitis | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Diverticulitis | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Enterobiasis | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Eye infection | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Fungal infection | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Gastroenteritis | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Hepatitis E | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Herpes zoster | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Influenza | 1/111 (0.9%) | 1 | 2/114 (1.8%) | 2 |
| Laryngitis | 0/111 (0%) | 0 | 2/114 (1.8%) | 2 |
| Lower respiratory tract infection | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Nasopharyngitis | 8/111 (7.2%) | 8 | 5/114 (4.4%) | 5 |
| Otitis media | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Pneumonia | 2/111 (1.8%) | 2 | 1/114 (0.9%) | 1 |
| Rhinitis | 0/111 (0%) | 0 | 4/114 (3.5%) | 4 |
| Sinusitis | 2/111 (1.8%) | 2 | 6/114 (5.3%) | 8 |
| Tonsillitis | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Upper respiratory tract infection | 4/111 (3.6%) | 4 | 7/114 (6.1%) | 8 |
| Urinary tract infection | 2/111 (1.8%) | 2 | 3/114 (2.6%) | 3 |
| Viral infection | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Pharyngotonsillitis | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Febrile infection | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Bronchitis viral | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Mycobacterial infection | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Respiratory tract infection | 1/111 (0.9%) | 2 | 0/114 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Ligament sprain | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Muscle strain | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Limb injury | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Bone contusion | 1/111 (0.9%) | 1 | 1/114 (0.9%) | 1 |
| Investigations | ||||
| Blood pressure decreased | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Blood pressure systolic increased | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Catheterisation cardiac | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Haemoglobin decreased | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Prothrombin time prolonged | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Hepatic enzyme increased | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| N-terminal prohormone brain natriuretic peptide increased | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Fluid retention | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Gout | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Hyperuricaemia | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Hypokalaemia | 0/111 (0%) | 0 | 4/114 (3.5%) | 4 |
| Iron deficiency | 2/111 (1.8%) | 2 | 4/114 (3.5%) | 4 |
| Decreased appetite | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Type 2 diabetes mellitus | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/111 (0.9%) | 1 | 3/114 (2.6%) | 3 |
| Arthritis | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Back pain | 1/111 (0.9%) | 1 | 6/114 (5.3%) | 6 |
| Muscle spasms | 2/111 (1.8%) | 2 | 1/114 (0.9%) | 1 |
| Musculoskeletal pain | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Myalgia | 1/111 (0.9%) | 1 | 1/114 (0.9%) | 1 |
| Neck pain | 2/111 (1.8%) | 2 | 1/114 (0.9%) | 1 |
| Pain in extremity | 0/111 (0%) | 0 | 1/114 (0.9%) | 2 |
| Pain in jaw | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Spinal osteoarthritis | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Systemic lupus erythematosus | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Intervertebral disc protrusion | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Nervous system disorders | ||||
| Diabetic neuropathy | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Dizziness | 5/111 (4.5%) | 5 | 2/114 (1.8%) | 2 |
| Headache | 14/111 (12.6%) | 16 | 8/114 (7%) | 8 |
| Hypoaesthesia | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Migraine | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Presyncope | 1/111 (0.9%) | 1 | 2/114 (1.8%) | 2 |
| Syncope | 0/111 (0%) | 0 | 2/114 (1.8%) | 2 |
| Psychiatric disorders | ||||
| Anxiety | 0/111 (0%) | 0 | 1/114 (0.9%) | 3 |
| Depression | 2/111 (1.8%) | 2 | 0/114 (0%) | 0 |
| Insomnia | 0/111 (0%) | 0 | 3/114 (2.6%) | 3 |
| Sleep disorder | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Stress | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Renal and urinary disorders | ||||
| Polyuria | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Urinary incontinence | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Reproductive system and breast disorders | ||||
| Dysmenorrhoea | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Menometrorrhagia | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Adnexa uteri cyst | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Cough | 0/111 (0%) | 0 | 7/114 (6.1%) | 7 |
| Dry throat | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Dyspnoea | 3/111 (2.7%) | 4 | 5/114 (4.4%) | 6 |
| Dyspnoea exertional | 2/111 (1.8%) | 3 | 0/114 (0%) | 0 |
| Epistaxis | 3/111 (2.7%) | 3 | 3/114 (2.6%) | 4 |
| Hypoxia | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Lung disorder | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Nasal congestion | 1/111 (0.9%) | 1 | 1/114 (0.9%) | 1 |
| Nasal polyps | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Productive cough | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Pulmonary embolism | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Pulmonary hypertension | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Pulmonary oedema | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Rhinitis allergic | 2/111 (1.8%) | 2 | 0/114 (0%) | 0 |
| Rhinorrhoea | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Sleep apnoea syndrome | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Throat irritation | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Paranasal sinus hypersecretion | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Pulmonary arterial hypertension | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Bronchial hyperreactivity | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Oropharyngeal pain | 0/111 (0%) | 0 | 2/114 (1.8%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| Acne | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Erythema | 1/111 (0.9%) | 1 | 0/114 (0%) | 0 |
| Hyperhidrosis | 1/111 (0.9%) | 1 | 1/114 (0.9%) | 1 |
| Pruritus | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Rash | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Surgical and medical procedures | ||||
| Tooth extraction | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Vascular disorders | ||||
| Circulatory collapse | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Flushing | 1/111 (0.9%) | 1 | 1/114 (0.9%) | 1 |
| Hypertension | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Hypotension | 13/111 (11.7%) | 19 | 6/114 (5.3%) | 11 |
| Orthostatic hypotension | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
| Jugular vein distension | 0/111 (0%) | 0 | 1/114 (0.9%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | Bayer |
| Phone | (+) 1-888-8422937 |
| clinical-trials-contact@bayer.com |
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT02891850
Other Study ID Numbers:
- 18588
- 2016-001067-36
First Posted:
Sep 8, 2016
Last Update Posted:
Feb 26, 2021
Last Verified:
Jan 1, 2021