Trial Outcomes & Findings for Measuring Outcomes In Patients With Pulmonary Arterial Hypertension Not on Active Treatment (MOTION) (NCT NCT02191137)

NCT ID: NCT02191137

Last Updated: 2017-10-13

Results Overview

The Living with Pulmonary Hypertension (LPH) questionnaire with Heart Failure questionnaire comprises 21 items, responded to on a 6-point Likert scale ranging from 0 'No' to 5 'Very much'. A total score ranging from 0 (best) to 105 (worst) is calculated by summing the responses to all 21 questions.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

75 participants

Primary outcome timeframe

Baseline to Week 24

Results posted on

2017-10-13

Participant Flow

A total of 97 patients signed informed consent; 22 patients did not complete screening (20 patients were screen failures and 2 patients withdrew from the study). Of 75 patients who received therapy with riociguat, 65 patients completed study treatment and entered follow-up, and 60 patients completed the study.

Participant milestones

Participant milestones
Measure	Riociguat (Adempas, BAY63-2521) Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Treatment STARTED	75
Treatment COMPLETED	65
Treatment NOT COMPLETED	10
Follow-up STARTED	65
Follow-up COMPLETED	60
Follow-up NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Riociguat (Adempas, BAY63-2521) Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Treatment Death	4
Treatment Withdrawal by Subject	3
Treatment Adverse Event	2
Treatment Other	1
Follow-up Lost to Follow-up	2
Follow-up Ongoing/unknown	2
Follow-up Adverse Event	1

Baseline Characteristics

Measuring Outcomes In Patients With Pulmonary Arterial Hypertension Not on Active Treatment (MOTION)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Riociguat (Adempas, BAY63-2521) n=75 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Age, Continuous	61.7 Years STANDARD_DEVIATION 11.4 • n=5 Participants
Sex: Female, Male Female	66 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Living with Pulmonary Hypertension (LPH) Total score	46.03 Scores STANDARD_DEVIATION 24.57 • n=5 Participants
Living with Pulmonary Hypertension (LPH) Physical dimension score	22.83 Scores STANDARD_DEVIATION 10.70 • n=5 Participants
Living with Pulmonary Hypertension (LPH) Emotional dimension score	10.20 Scores STANDARD_DEVIATION 7.80 • n=5 Participants
Short Form-12 Health Survey (SF-12) questionnaire Physical component summary	36.660 Scores STANDARD_DEVIATION 8.577 • n=5 Participants
Short Form-12 Health Survey (SF-12) questionnaire Mental component summary	47.453 Scores STANDARD_DEVIATION 9.213 • n=5 Participants
WHO functional class I	9.3 Percentage of participants n=5 Participants
WHO functional class II	30.7 Percentage of participants n=5 Participants
WHO functional class III	58.7 Percentage of participants n=5 Participants
WHO functional class IV	1.3 Percentage of participants n=5 Participants
Modified Borg Dyspnea Scale	4.47 Scores STANDARD_DEVIATION 2.74 • n=5 Participants
Six-minute walk distance (6MWD)	310.259 Meters STANDARD_DEVIATION 89.578 • n=5 Participants
Work Limitations Questionnaire (WLQ) Time management scale	36.42 Percentage STANDARD_DEVIATION 30.82 • n=5 Participants
Work Limitations Questionnaire (WLQ) Physical demands scale	33.47 Percentage STANDARD_DEVIATION 28.25 • n=5 Participants
Work Limitations Questionnaire (WLQ) Mental-interpersonal demands scale	28.66 Percentage STANDARD_DEVIATION 25.22 • n=5 Participants
Work Limitations Questionnaire (WLQ) Output demands scale	36.52 Percentage STANDARD_DEVIATION 31.51 • n=5 Participants
WLQ: Percentage of Productivity loss	8.85 Percentage STANDARD_DEVIATION 6.62 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: The ITT analysis set was synonymous with the Safety analysis set definition which included all patients who received at least 1 dose of test drug. 66 patients were evaluable for LPH total score at Week 24.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=66 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Baseline to Week 24 in the Living With Pulmonary Hypertension (LPH) Questionnaire Total Score	-10.99 Scores Standard Deviation 22.51

SECONDARY outcome

Timeframe: Baseline to Week 4 and Week 16

Population: The ITT analysis set was synonymous with the Safety analysis set definition which included all patients who received at least 1 dose of test drug. 72 patients were evaluable for LPH total score at Week 4.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=72 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Baseline to Weeks 4 and 16 in the LPH Total Score Week 4 (N=72)	-7.65 Scores Standard Deviation 18.30
Change From Baseline to Weeks 4 and 16 in the LPH Total Score Week 16 (N=68)	-6.98 Scores Standard Deviation 20.85

SECONDARY outcome

Timeframe: Week 16 to Week 24

Population: The Completers analysis set included patients valid for Safety/ITT analysis sets who had an LPH score at baseline (Visit 1), Week 4, Week 16, and Week 24. 58 patients in Completer analysis set were evaluable for LPH total score at Week 24.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=58 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Week 16 to Week 24 in the LPH Total Score (Completers Analysis Set Only)	-1.66 Scores Standard Deviation 15.13

SECONDARY outcome

Timeframe: Baseline to Weeks 4, 16, and 24

Population: The ITT analysis set was synonymous with the Safety analysis set definition which included all patients who received at least 1 dose of test drug. 75 patients were evaluable for LPH physical dimension score at week 16 or before.

The LPH derived from the Minnesota Living with Heart Failure questionnaire comprises 21 items, responded to on a 6-point Likert scale ranging from 0 'No' to 5 'Very much'. A total score ranging from 0 to 105 is calculated by summing the responses to all 21 questions. A physical dimension score (range 0-40, 8 items) and an emotional dimension score (range 0-25, 5 items) can also be calculated. For all LPH scores, a higher score indicates that patients are more affected by their medical condition. In the below table, "N" signifies subjects who were evaluable for the specific parameter at that timepoint.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=75 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Baseline to Weeks 4, 16, and 24 in the LPH Physical Dimension Score Week 4 (N=72)	-3.77 Scores Standard Deviation 8.25
Change From Baseline to Weeks 4, 16, and 24 in the LPH Physical Dimension Score Week 16 or Last Before (N=75)	-3.97 Scores Standard Deviation 9.94
Change From Baseline to Weeks 4, 16, and 24 in the LPH Physical Dimension Score Week 24 (N=65)	-6.10 Scores Standard Deviation 9.38

SECONDARY outcome

Timeframe: Week 16 to Week 24

Population: The Completers analysis set included patients valid for Safety/ITT analysis sets who had an LPH score at baseline (Visit 1), Week 4, Week 16, and Week 24. 57 patients in Completer analysis set were evaluable for LPH physical dimension score at Week 24.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=57 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Week 16 to Week 24 in the LPH Physical Dimension Score (Completers Analysis Set Only)	-0.86 Scores Standard Deviation 7.20

SECONDARY outcome

Timeframe: Baseline to Week 4, Week 16 and Week 24

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=75 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Baseline to Weeks 4, 16, and 24 in the LPH Emotional Dimension Score Week 4 (N=72)	-2.22 Scores Standard Deviation 5.70
Change From Baseline to Weeks 4, 16, and 24 in the LPH Emotional Dimension Score Week 16 or Last Before (N=75)	-1.44 Scores Standard Deviation 7.32
Change From Baseline to Weeks 4, 16, and 24 in the LPH Emotional Dimension Score Week 24 (N=66)	-2.33 Scores Standard Deviation 6.90

SECONDARY outcome

Timeframe: Week 16 to Week 24

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=58 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Week 16 to Week 24 in the LPH Emotional Dimension Score (Completers Analysis Set Only)	-0.11 Scores Standard Deviation 5.50

SECONDARY outcome

Timeframe: Baseline to Week 4, Week 16 and Week 24

For LPH total score, the MCID was an 11-point decrease from baseline. In the below table, "N" signifies subjects who were evaluable for the specific parameter at that timepoint.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=72 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Percentage of Patients With a Minimal Clinically Significant Important Difference (MCID) From Baseline in LPH Total Score at Weeks 4, 16, and 24 Week 4 (N=72)	38.9 Percentage of participants Interval 0.34 to 0.58
Percentage of Patients With a Minimal Clinically Significant Important Difference (MCID) From Baseline in LPH Total Score at Weeks 4, 16, and 24 Week 16 (N=68)	45.6 Percentage of participants Interval 0.39 to 0.64
Percentage of Patients With a Minimal Clinically Significant Important Difference (MCID) From Baseline in LPH Total Score at Weeks 4, 16, and 24 Week 24 (N=66)	47.0 Percentage of participants Interval 0.47 to 0.72

SECONDARY outcome

Timeframe: Baseline to Week 4, Week 16 and Week 24

For the physical and emotional dimension scores, the MCID was a 4-point decrease. In the below table, "N" signifies subjects who were evaluable for the specific parameter at that timepoint.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=72 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Percentage of Patients With an MCID From Baseline in LPH Physical Dimension Score at Weeks 4, 16, and 24 Week 4 (N=72)	45.8 Percentage of Participants
Percentage of Patients With an MCID From Baseline in LPH Physical Dimension Score at Weeks 4, 16, and 24 Week 16 (N=68)	51.5 Percentage of Participants
Percentage of Patients With an MCID From Baseline in LPH Physical Dimension Score at Weeks 4, 16, and 24 Week 24 (N=65)	60.0 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline to Week 4, Week 16 and Week 24

For the physical and emotional dimension scores, the MCID was a 4-point decrease. In the below table, "N" signifies subjects who were evaluable for the specific parameter at that timepoint.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=72 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Percentage of Patients With an MCID From Baseline in LPH Emotional Dimension Score at Weeks 4, 16, and 24 Week 4 (N=72)	31.9 Percentage of Participants
Percentage of Patients With an MCID From Baseline in LPH Emotional Dimension Score at Weeks 4, 16, and 24 Week 16 (N=68)	39.7 Percentage of Participants
Percentage of Patients With an MCID From Baseline in LPH Emotional Dimension Score at Weeks 4, 16, and 24 Week 24 (N=66)	33.3 Percentage of Participants

SECONDARY outcome

Timeframe: Week 16 to Week 24

For LPH total score, the MCID was an 11-point decrease.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=58 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Percentage of Patients With an MCID From Week 16 in LPH Total Score at Week 24 (Completers Analysis Set Only)	24.1 Percentage of Participants

SECONDARY outcome

Timeframe: Week 16 to Week 24

Population: The Completers analysis set included patients valid for Safety/ITT analysis sets who had an LPH score at baseline (Visit 1), Week 4, Week 16, and Week 24. 57 patients were evaluable for LPH physical dimension score at week 24.

For the physical and emotional dimension scores, the MCID was a 4-point decrease.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=57 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Percentage of Patients With an MCID From Week 16 in Physical Dimension Score at Week 24 (Completers Analysis Set Only)	29.8 Percentage of Participants

SECONDARY outcome

Timeframe: Week 16 to Week 24

For the physical and emotional dimension scores, the MCID was a 4-point decrease.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=58 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Percentage of Patients With an MCID From Week 16 in Emotional Dimension Score at Week 24 (Completers Analysis Set Only)	17.2 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline to Week 4, Week 16 and Week 24

Population: The ITT analysis set was synonymous with the Safety analysis set definition which included all patients who received at least 1 dose of test drug. 52 patients were evaluable for WLQ at week 4.

The Work Limitations Questionnaire (WLQ) is an 8-item questionnaire that measures the degree to which employed individuals are experiencing limitations on-the-job due to their health problems, and health-related productivity loss (Presenteeism). The WLQ's terms are aggregated into four scales (i.e. Time Management, Physical demands, Mental-interpersonal demands, Output demands). Scale score range from 0 (limited none of the time) to 100 (limited all of the time) and represent the reported amount of time in the prior two weeks respondents were limited on-the-job. In the below table, "N" signifies subjects who were evaluable for the specific parameter at that timepoint.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=52 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores Week 4 Time management score, N=45	4.17 Scores Standard Deviation 25.28
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores Week 4 Physical demands score, N=52	0.96 Scores Standard Deviation 25.35
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores Week 4 Mental-interpersonal demands score, N=48	-8.59 Scores Standard Deviation 25.29
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores Week 4 Output demands score, N=40	-6.88 Scores Standard Deviation 27.00
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores Week 16 Time management score, N=45	0.56 Scores Standard Deviation 26.24
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores Week 16 Physical demands score, N=49	7.40 Scores Standard Deviation 26.26
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores Week 16 Mental-interpersonal demands score, N=46	-6.52 Scores Standard Deviation 24.82
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores Week 16 Output demands score, N=40	2.81 Scores Standard Deviation 25.71
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores Week 24 Time management score, N=42	-2.68 Scores Standard Deviation 26.41
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores Week 24 Physical demands score, N=43	2.33 Scores Standard Deviation 21.17
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores Week 24 Mental-interpersonal demands score, N=41	-2.13 Scores Standard Deviation 25.91
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores Week 24 Output demands score, N=34	-2.57 Scores Standard Deviation 25.71

SECONDARY outcome

Timeframe: Baseline to Week 4, Week 16 and Week 24

Population: The ITT analysis set was synonymous with the Safety analysis set definition which included all patients who received at least 1 dose of test drug. 37 patients were evaluable for WLQ percentage of productivity loss at week 4.

The WLQ is an 8-item questionnaire that measures the degree to which employed individuals are experiencing limitations on-the-job due to their health problems, and health-related productivity loss (Presenteeism). The WLQ's terms are aggregated into four scales (i.e. Time Management, Physical demands, Mental-interpersonal demands, Output demands). Using an algorithm, WLQ scale scores can be converted into an estimate of productivity loss. In the below table, "N" signifies subjects who were evaluable for the specific parameter at that timepoint.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=52 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Percentage of Productivity Loss Week 4 Productivity loss (%), N=37	-1.07 Percentage Standard Deviation 4.68
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Percentage of Productivity Loss Week 16 Productivity loss (%), N=30	0.54 Percentage Standard Deviation 4.85
Change From Baseline to Weeks 4, 16, and 24 in the WLQ Percentage of Productivity Loss Week 24 Productivity loss (%), N=27	-0.53 Percentage Standard Deviation 5.82

SECONDARY outcome

Timeframe: Week 16 to Week 24

Population: The Completers analysis set included patients valid for Safety/ITT analysis sets who had an LPH score at baseline (Visit 1), Week 4, Week 16, and Week 24. 40 patients in Completer analysis set were evaluable for WLQ at Week 24.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=40 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Week 16 to Week 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands, and Output Demands Scores (Completers Analysis Set Only) Time management score, N=39	-0.32 Scores Standard Deviation 25.73
Change From Week 16 to Week 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands, and Output Demands Scores (Completers Analysis Set Only) Physical demands score, N=40	-1.56 Scores Standard Deviation 24.22
Change From Week 16 to Week 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands, and Output Demands Scores (Completers Analysis Set Only) Mental-interpersonal demands score, N=38	5.92 Scores Standard Deviation 19.87
Change From Week 16 to Week 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands, and Output Demands Scores (Completers Analysis Set Only) Output demands score, N=34	-4.78 Scores Standard Deviation 24.43

SECONDARY outcome

Timeframe: Week 16 to Week 24

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=40 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Week 16 to Week 24 in the WLQ Percentage of Productivity Loss (Completers Analysis Set Only)	0.19 Percentage Standard Deviation 4.17

SECONDARY outcome

Timeframe: Baseline to Week 4, Week 16 and Week 24

Population: The ITT analysis set was synonymous with the Safety analysis set definition which included all patients who received at least 1 dose of test drug. 73 patients were evaluable for PCS and MCS at Week 4.

SF-12v2® Health Survey is a 12-item questionnaire to measure functional health and well-being from the patient's point of view. Physical and Mental Health Composite Scores (PCS \& MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. In the below table, "N" signifies subjects who were evaluable for the specific parameter at that timepoint.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=73 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Baseline to Weeks 4, 16, and 24 in the Short Form-12 Health Survey (SF-12) Physical Component Summary (PCS) Score and Mental Component Summary (MCS) Score PCS Week 4 (N=73)	1.009 Scores Standard Deviation 6.474
Change From Baseline to Weeks 4, 16, and 24 in the Short Form-12 Health Survey (SF-12) Physical Component Summary (PCS) Score and Mental Component Summary (MCS) Score PCS Week 16 (N=69)	0.036 Scores Standard Deviation 7.059
Change From Baseline to Weeks 4, 16, and 24 in the Short Form-12 Health Survey (SF-12) Physical Component Summary (PCS) Score and Mental Component Summary (MCS) Score PCS Week 24 (N=67)	1.230 Scores Standard Deviation 8.401
Change From Baseline to Weeks 4, 16, and 24 in the Short Form-12 Health Survey (SF-12) Physical Component Summary (PCS) Score and Mental Component Summary (MCS) Score MCS Week 4 (N=73)	1.955 Scores Standard Deviation 9.262
Change From Baseline to Weeks 4, 16, and 24 in the Short Form-12 Health Survey (SF-12) Physical Component Summary (PCS) Score and Mental Component Summary (MCS) Score MCS Week 16 (N=69)	1.869 Scores Standard Deviation 7.605
Change From Baseline to Weeks 4, 16, and 24 in the Short Form-12 Health Survey (SF-12) Physical Component Summary (PCS) Score and Mental Component Summary (MCS) Score MCS Week 24 (N=67)	2.883 Scores Standard Deviation 10.073

SECONDARY outcome

Timeframe: Week 16 to Week 24

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=58 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Week 16 to Week 24 in the SF-12 PCS Score and MCS Score (Completers Analysis Set Only) PCS	1.383 Scores Standard Deviation 6.810
Change From Week 16 to Week 24 in the SF-12 PCS Score and MCS Score (Completers Analysis Set Only) MCS	0.437 Scores Standard Deviation 8.378

SECONDARY outcome

Timeframe: Baseline to Week 4, Week 16 and Week 24

Functional class was determined by the WHO classification: I: Patients with PH (pulmonary hypertension) but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope. II: Patients with PH resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope. III: Patients with PH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. IV: Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity. In the below table, "N" signifies subjects who were evaluable for the specific parameter at that timepoint.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=75 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class Week 4 (-1 Change in WHO Class), N=72	9.7 Percentage of participants
Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class Week 4 (0 Change in WHO Class), N=72	87.5 Percentage of participants
Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class Week 4 (+1 Change in WHO Class), N=72	2.8 Percentage of participants
Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class Week 4 (+2 Change in WHO Class), N=72	0 Percentage of participants
Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class Week 16 or LastBefore (-1 Change in WHOClass),N=75	18.7 Percentage of participants
Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class Week 16 or LastBefore (0 Change in WHOClass),N=75	66.7 Percentage of participants
Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class Week 16 or LastBefore (+1 Change in WHOClass),N=75	12.0 Percentage of participants
Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class Week 16 or LastBefore (+2 Change in WHOClass),N=75	2.7 Percentage of participants
Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class Week 24 (-1 Change in WHO Class), N=67	28.4 Percentage of participants
Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class Week 24 (0 Change in WHO Class), N=67	64.2 Percentage of participants
Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class Week 24 (+1 Change in WHO Class), N=67	6.0 Percentage of participants
Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class Week 24 (+2 Change in WHO Class), N=67	1.5 Percentage of participants

SECONDARY outcome

Timeframe: Week 16 to Week 24

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=57 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Week 16 to Week 24 in the WHO Functional Class (Completers Analysis Set Only) -2 Change in WHO Class	1.8 Percentage of participants
Change From Week 16 to Week 24 in the WHO Functional Class (Completers Analysis Set Only) -1 Change in WHO Class	15.8 Percentage of participants
Change From Week 16 to Week 24 in the WHO Functional Class (Completers Analysis Set Only) 0 Change in WHO Class	70.2 Percentage of participants
Change From Week 16 to Week 24 in the WHO Functional Class (Completers Analysis Set Only) +1 Change in WHO Class	10.5 Percentage of participants
Change From Week 16 to Week 24 in the WHO Functional Class (Completers Analysis Set Only) +2 Change in WHO Class	1.8 Percentage of participants

SECONDARY outcome

Timeframe: Week 16 to Week 24

Population: The ITT analysis set was synonymous with the Safety analysis set definition which included all patients who received at least 1 dose of test drug. 58 patients were evaluable for Modified Borg Dyspnea Scale at week 24.

The Modified Borg Dyspnea Scale assessed the intensity of the patient's dyspnea from 0 (best) to 10 (worst). In the below table, "N" signifies subjects who were evaluable for the specific parameter at that timepoint.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=58 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Baseline to Weeks 16 and 24 in the Modified Borg Dyspnea Scale Week 16 (N=57)	-0.70 Scores Standard Deviation 3.23
Change From Baseline to Weeks 16 and 24 in the Modified Borg Dyspnea Scale Week 24 (N=58)	-0.91 Scores Standard Deviation 3.44

SECONDARY outcome

Timeframe: Week 16 to Week 24

The Modified Borg Dyspnea Scale assessed the intensity of the patient's dyspnea from 0 (best) to 10 (worst).

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=57 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Week 16 to Week 24 in the Modified Borg Dyspnea Scale (Completers Analysis Set Only)	-0.19 Scores Standard Deviation 3.75

SECONDARY outcome

Timeframe: Week 16 to Week 24

Population: The ITT analysis set was synonymous with the Safety analysis set definition which included all patients who received at least 1 dose of test drug. 67 patients were evaluable for 6MWD at week 24.

Six-minute walk distance (6MWD) was conducted to test the physical limitations of the patient by assessing the patient's exercise capacity. The distance walked by the patient in 6 minutes was measured. In the below table, "N" signifies subjects who were evaluable for the specific parameter at that timepoint.

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=67 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Baseline to Weeks 16 and 24 in the 6MWD Week 16 (N=66)	2.362 Meters Standard Deviation 75.506
Change From Baseline to Weeks 16 and 24 in the 6MWD Week 24 (N=67)	-2.921 Meters Standard Deviation 59.247

SECONDARY outcome

Timeframe: Week 16 to Week 24

Outcome measures

Outcome measures
Measure	Riociguat (Adempas, BAY63-2521) n=57 Participants Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Change From Week 16 to Week 24 in the 6MWD (Completers Analysis Set Only)	-7.932 Meters Standard Deviation 71.542

Adverse Events

Riociguat (Adempas, BAY63-2521)

Serious events: 21 serious events

Other events: 61 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Riociguat (Adempas, BAY63-2521) n=75 participants at risk Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Hepatobiliary disorders Cholestasis	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Hepatobiliary disorders Hepatic steatosis	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Infections and infestations Pneumonia	4.0% 3/75 • Number of events 4 • From the first dose of test drug up to 2 days after the last dose.
Infections and infestations Sepsis	2.7% 2/75 • Number of events 2 • From the first dose of test drug up to 2 days after the last dose.
Infections and infestations Urinary tract infection	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Infections and infestations Bronchitis viral	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Metabolism and nutrition disorders Fluid overload	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Blood and lymphatic system disorders Anaemia	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Blood and lymphatic system disorders Iron deficiency anaemia	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Cardiac disorders Atrial fibrillation	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Cardiac disorders Cardiac failure acute	2.7% 2/75 • Number of events 2 • From the first dose of test drug up to 2 days after the last dose.
Cardiac disorders Cardiac failure congestive	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Cardiac disorders Acute left ventricular failure	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Gastrointestinal disorders Abdominal pain	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Gastrointestinal disorders Gastritis	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Gastrointestinal disorders Rectal haemorrhage	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Gastrointestinal disorders Retroperitoneal haemorrhage	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
General disorders Chest pain	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
General disorders Oedema peripheral	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Hepatobiliary disorders Cholecystitis acute	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Metabolism and nutrition disorders Hypokalaemia	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Metabolism and nutrition disorders Hyponatraemia	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Musculoskeletal and connective tissue disorders Back pain	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Renal and urinary disorders Acute kidney injury	2.7% 2/75 • Number of events 2 • From the first dose of test drug up to 2 days after the last dose.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	2.7% 2/75 • Number of events 2 • From the first dose of test drug up to 2 days after the last dose.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.0% 3/75 • Number of events 3 • From the first dose of test drug up to 2 days after the last dose.
Respiratory, thoracic and mediastinal disorders Hypoxia	4.0% 3/75 • Number of events 3 • From the first dose of test drug up to 2 days after the last dose.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Respiratory, thoracic and mediastinal disorders Respiratory distress	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.7% 2/75 • Number of events 2 • From the first dose of test drug up to 2 days after the last dose.
Surgical and medical procedures Cardiac resynchronisation therapy	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Vascular disorders Aortic dissection	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.
Vascular disorders Hypotension	1.3% 1/75 • Number of events 1 • From the first dose of test drug up to 2 days after the last dose.

Other adverse events

Other adverse events
Measure	Riociguat (Adempas, BAY63-2521) n=75 participants at risk Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.
Cardiac disorders Palpitations	5.3% 4/75 • Number of events 4 • From the first dose of test drug up to 2 days after the last dose.
Gastrointestinal disorders Abdominal pain	5.3% 4/75 • Number of events 4 • From the first dose of test drug up to 2 days after the last dose.
Gastrointestinal disorders Constipation	10.7% 8/75 • Number of events 8 • From the first dose of test drug up to 2 days after the last dose.
Gastrointestinal disorders Diarrhoea	18.7% 14/75 • Number of events 18 • From the first dose of test drug up to 2 days after the last dose.
Gastrointestinal disorders Dyspepsia	20.0% 15/75 • Number of events 24 • From the first dose of test drug up to 2 days after the last dose.
Gastrointestinal disorders Gastrooesophageal reflux disease	10.7% 8/75 • Number of events 8 • From the first dose of test drug up to 2 days after the last dose.
Gastrointestinal disorders Nausea	21.3% 16/75 • Number of events 18 • From the first dose of test drug up to 2 days after the last dose.
Gastrointestinal disorders Vomiting	12.0% 9/75 • Number of events 10 • From the first dose of test drug up to 2 days after the last dose.
General disorders Chest pain	10.7% 8/75 • Number of events 8 • From the first dose of test drug up to 2 days after the last dose.
General disorders Fatigue	13.3% 10/75 • Number of events 10 • From the first dose of test drug up to 2 days after the last dose.
General disorders Oedema peripheral	12.0% 9/75 • Number of events 10 • From the first dose of test drug up to 2 days after the last dose.
General disorders Peripheral swelling	5.3% 4/75 • Number of events 4 • From the first dose of test drug up to 2 days after the last dose.
Infections and infestations Bronchitis	5.3% 4/75 • Number of events 4 • From the first dose of test drug up to 2 days after the last dose.
Infections and infestations Influenza	5.3% 4/75 • Number of events 4 • From the first dose of test drug up to 2 days after the last dose.
Infections and infestations Nasopharyngitis	12.0% 9/75 • Number of events 9 • From the first dose of test drug up to 2 days after the last dose.
Infections and infestations Pneumonia	5.3% 4/75 • Number of events 4 • From the first dose of test drug up to 2 days after the last dose.
Infections and infestations Sinusitis	5.3% 4/75 • Number of events 4 • From the first dose of test drug up to 2 days after the last dose.
Infections and infestations Urinary tract infection	5.3% 4/75 • Number of events 4 • From the first dose of test drug up to 2 days after the last dose.
Metabolism and nutrition disorders Hypokalaemia	5.3% 4/75 • Number of events 4 • From the first dose of test drug up to 2 days after the last dose.
Musculoskeletal and connective tissue disorders Arthralgia	6.7% 5/75 • Number of events 5 • From the first dose of test drug up to 2 days after the last dose.
Musculoskeletal and connective tissue disorders Back pain	9.3% 7/75 • Number of events 7 • From the first dose of test drug up to 2 days after the last dose.
Nervous system disorders Dizziness	22.7% 17/75 • Number of events 20 • From the first dose of test drug up to 2 days after the last dose.
Nervous system disorders Headache	17.3% 13/75 • Number of events 15 • From the first dose of test drug up to 2 days after the last dose.
Psychiatric disorders Insomnia	6.7% 5/75 • Number of events 5 • From the first dose of test drug up to 2 days after the last dose.
Respiratory, thoracic and mediastinal disorders Cough	8.0% 6/75 • Number of events 6 • From the first dose of test drug up to 2 days after the last dose.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.7% 8/75 • Number of events 9 • From the first dose of test drug up to 2 days after the last dose.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.3% 4/75 • Number of events 4 • From the first dose of test drug up to 2 days after the last dose.
Vascular disorders Hypotension	12.0% 9/75 • Number of events 11 • From the first dose of test drug up to 2 days after the last dose.

Additional Information

Therapeutic Area Head

BAYER

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60