Trial Outcomes & Findings for BAY63-2521:Long-term Extension Study in Patients With Pulmonary Arterial Hypertension (NCT NCT00863681)

NCT ID: NCT00863681

Last Updated: 2023-11-07

Results Overview

Analyses of drug-related TEAEs were based on the assessment of causal relationship to study medication.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

396 participants

Primary outcome timeframe

From administration of first dose of study medication in PATENT-2 up to 2 days after end of treatment with study medication, up to 10 years and 5 months.

Results posted on

2023-11-07

Participant Flow

Study was conducted at 97 centers in 27 countries between 12-MAR-2009 (first participant first visit) and 19-AUG-2019 (last participant last visit);

Of the 405 participants who completed PATENT-1(NCT00810693) study, 396 participants entered PATENT-2 study. 231 participants were from the former riociguat 1.0-2.5mg group, 109 were from the former placebo group and 56 were from the former riociguat 1.0-1.5mg group.

Participant milestones

Participant milestones
Measure	Riociguat-Former Riociguat 1.0-2.5 mg Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Overall Study STARTED	231	109	56
Overall Study COMPLETED	140	66	38
Overall Study NOT COMPLETED	91	43	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Riociguat-Former Riociguat 1.0-2.5 mg Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Overall Study Other	2	0	0
Overall Study Missing	1	0	0
Overall Study Death	40	23	6
Overall Study Withdrawal by Subject	12	5	2
Overall Study Protocol Violation	2	0	0
Overall Study Lost to Follow-up	3	0	3
Overall Study Adverse Event	28	10	6
Overall Study Lack of Efficacy	2	2	1
Overall Study Non-compliance with study drug	1	3	0

Baseline Characteristics

BAY63-2521:Long-term Extension Study in Patients With Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=231 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Total n=396 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	174 Participants n=5 Participants	87 Participants n=7 Participants	45 Participants n=5 Participants	306 Participants n=4 Participants
Age, Categorical >=65 years	57 Participants n=5 Participants	22 Participants n=7 Participants	11 Participants n=5 Participants	90 Participants n=4 Participants
Age, Continuous	50.4 years STANDARD_DEVIATION 16.4 • n=5 Participants	48.8 years STANDARD_DEVIATION 15.9 • n=7 Participants	48.2 years STANDARD_DEVIATION 16.3 • n=5 Participants	49.7 years STANDARD_DEVIATION 16.2 • n=4 Participants
Sex: Female, Male Female	186 Participants n=5 Participants	87 Participants n=7 Participants	44 Participants n=5 Participants	317 Participants n=4 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	22 Participants n=7 Participants	12 Participants n=5 Participants	79 Participants n=4 Participants
Race/Ethnicity, Customized White	148 Participants n=5 Participants	66 Participants n=7 Participants	28 Participants n=5 Participants	242 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Asian	74 Participants n=5 Participants	33 Participants n=7 Participants	20 Participants n=5 Participants	127 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	7 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	22 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: From administration of first dose of study medication in PATENT-2 up to 2 days after end of treatment with study medication, up to 10 years and 5 months.

Analyses of drug-related TEAEs were based on the assessment of causal relationship to study medication.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=231 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Number of Participants With Treatment-emergent Adverse Events (TEAE) Any drug-related TEAE	138 Participants	74 Participants	30 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAE) Any serious TEAE	161 Participants	76 Participants	39 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAE) Any TEAE	229 Participants	108 Participants	56 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAE) Any drug-related serious TEAE	25 Participants	16 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAE) Any TEAE leading to death	42 Participants	25 Participants	6 Participants

PRIMARY outcome

Timeframe: From baseline to end of safety follow-up visit, up to 10 years and 6 months (1 month more than End of study visit)

Analyses of deaths were based on the assessment of causal relationship to study medication. The safety follow-up visit was to be performed 30 days after the last dose of riociguat.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=231 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Number of Participant With Death	48 Participants	30 Participants	7 Participants

SECONDARY outcome

Timeframe: From baseline to termination visit, up to 10 years

Population: Participants in SAF with evaluable data for each visit, and for each parameter.

Percentage of participants only with a treatment-emergent shift in hematology and coagulation parameters from normal or low at baseline to a high value at a timepoint after the start of treatment. The percentage was calculated by comparing the number of participants with a normal or low value at baseline who had at least one high value after the start of treatment with the number of participants with a normal or low value at baseline who also had at least one valid value after start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=209 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=93 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=49 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation aPTT (Sec)	68.1 Percentage of participants	80.0 Percentage of participants	79.2 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Basophils (Giga/L)	1.0 Percentage of participants	1.1 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Basophils/Leukocytes (%)	16.4 Percentage of participants	12.1 Percentage of participants	10.4 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Eosinophils (Giga/L)	1.9 Percentage of participants	2.2 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Eosinophils/Leukocytes (%)	8.7 Percentage of participants	3.4 Percentage of participants	10.4 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Erythrocytes (T/L)	13.7 Percentage of participants	21.8 Percentage of participants	35.0 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Hematocrit (%)	35.6 Percentage of participants	37.7 Percentage of participants	48.6 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Hemoglobin (g/dL)	8.9 Percentage of participants	16.5 Percentage of participants	24.4 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Leukocytes (Giga/L)	10.9 Percentage of participants	13.6 Percentage of participants	22.2 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Lymphocytes (Giga/L)	1.4 Percentage of participants	3.4 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Lymphocytes/Leukocytes (%)	11.4 Percentage of participants	19.5 Percentage of participants	6.5 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Monocytes (Giga/L)	6.3 Percentage of participants	3.3 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Monocytes/Leukocytes (%)	20.0 Percentage of participants	18.0 Percentage of participants	22.2 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Neutrophils (Giga/L)	14.2 Percentage of participants	18.8 Percentage of participants	28.3 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Neutrophils/Leukocytes (%)	42.5 Percentage of participants	38.3 Percentage of participants	52.3 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Platelets (Giga/L)	14.9 Percentage of participants	9.7 Percentage of participants	15.6 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation Prothrombin INR	56.3 Percentage of participants	74.0 Percentage of participants	58.6 Percentage of participants

SECONDARY outcome

Timeframe: From baseline to termination visit, up to 10 years

Population: Participants in SAF with evaluable data for each visit, and for each parameter.

Percentage of participants only with a treatment-emergent shift in hematology and coagulation parameters from normal or high at baseline to a low value at a timepoint after the start of treatment. The percentage was calculated by comparing the number of participants with a normal or high value at baseline who had at least one low value after the start of treatment with the number of participants with a normal or high value at baseline who also had at least one valid value after start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=211 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=96 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=49 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation aPTT (Sec)	12.8 Percentage of participants	13.5 Percentage of participants	8.5 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation Erythrocytes (T/L)	31.0 Percentage of participants	22.8 Percentage of participants	25.0 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation Hematocrit (%)	22.1 Percentage of participants	23.3 Percentage of participants	26.7 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation Hemoglobin (g/dL)	48.2 Percentage of participants	38.0 Percentage of participants	46.2 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation Leukocytes (Giga/L)	25.7 Percentage of participants	23.6 Percentage of participants	25.6 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation Lymphocytes (Giga/L)	29.3 Percentage of participants	29.3 Percentage of participants	32.6 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation Lymphocytes/Leukocytes (%)	50.3 Percentage of participants	44.6 Percentage of participants	64.3 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation Monocytes (Giga/L)	0.5 Percentage of participants	1.1 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation Monocytes/Leukocytes (%)	2.4 Percentage of participants	3.3 Percentage of participants	14.3 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation Neutrophils (Giga/L)	9.4 Percentage of participants	4.4 Percentage of participants	8.5 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation Neutrophils/Leukocytes (%)	6.9 Percentage of participants	4.5 Percentage of participants	6.5 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation Platelets (Giga/L)	23.8 Percentage of participants	29.5 Percentage of participants	26.8 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation Prothrombin INR	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: From baseline to termination visit, up to 10 years

Population: Participants in SAF with evaluable data for each visit, and for each parameter.

Percentage of participants per treatment group only with a treatment-emergent shift in clinical chemistry parameters from normal or low at baseline to a high value at a timepoint after the start of treatment. The percentage was calculated by comparing the number of participants with a normal or low value at baseline who had at least one high value after the start of treatment with the number of participants with a normal or low value at baseline who also had at least one valid value after start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=222 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=103 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=52 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Alanine Aminotransferase (U/L)	13.4 Percentage of participants	12.0 Percentage of participants	8.7 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Albumin (g/dL)	0.5 Percentage of participants	1.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Alkaline Phosphatase (U/L)	15.7 Percentage of participants	23.4 Percentage of participants	15.6 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Aspartate Aminotransferase (U/L)	11.6 Percentage of participants	11.5 Percentage of participants	10.6 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Bilirubin (mg/dL)	14.5 Percentage of participants	11.8 Percentage of participants	28.9 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Calcium(mg/dL)	2.5 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Creatine Kinase (U/L)	23.8 Percentage of participants	24.7 Percentage of participants	19.1 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Creatinine (mg/dL)	29.4 Percentage of participants	39.7 Percentage of participants	45.5 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Gamma Glutamyl Transferase(U/L)	18.2 Percentage of participants	17.1 Percentage of participants	25.0 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Glutamate Dehydrogenase (U/L)	40.0 Percentage of participants	37.7 Percentage of participants	56.8 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Phosphate (mg/dL)	2.6 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Potassium (mmol/L)	4.6 Percentage of participants	4.9 Percentage of participants	8.0 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Protein (g/dL)	2.3 Percentage of participants	4.9 Percentage of participants	3.8 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Pseudocholinesterase (U/mL)	0.5 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Sodium (mmol/L)	0.5 Percentage of participants	1.9 Percentage of participants	3.8 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Triacylglycerol Lipase (U/L)	22.6 Percentage of participants	19.3 Percentage of participants	12.2 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Urate (mg/dL)	24.3 Percentage of participants	25.3 Percentage of participants	29.3 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Urea (mg/dL)	20.1 Percentage of participants	18.9 Percentage of participants	30.4 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry eGFR - MDRD Method (mL/min/1.73 m*2)	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry Creatinine Clearance (mL/min)	12.1 Percentage of participants	15.4 Percentage of participants	13.3 Percentage of participants

SECONDARY outcome

Timeframe: From baseline to termination visit, up to 10 years

Population: Participants in SAF with evaluable data for each visit, and for each parameter.

Percentage of participants per treatment group only with a treatment-emergent shift in clinical chemistry parameters from normal or high at baseline to a low value at a timepoint after the start of treatment. The percentage was calculated by comparing the number of participants with a normal or high value at baseline who had at least one low value after the start of treatment with the number of participants with a normal or high value at baseline who also had at least one valid value after start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=223 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=103 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=52 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Alanine Aminotransferase (U/L)	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Albumin (g/dL)	4.1 Percentage of participants	4.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Alkaline Phosphatase (U/L)	3.3 Percentage of participants	4.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Bilirubin (mg/dL)	0.0 Percentage of participants	1.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Calcium (mg/dL)	25.0 Percentage of participants	10.0 Percentage of participants	20.0 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Creatine Kinase (U/L)	8.7 Percentage of participants	5.1 Percentage of participants	12.2 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Creatinine (mg/dL)	4.5 Percentage of participants	6.9 Percentage of participants	5.8 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Gamma Glutamyl Transferase (U/L)	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Phosphate (mg/dL)	5.3 Percentage of participants	15.4 Percentage of participants	33.3 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Potassium (mmol/L)	24.9 Percentage of participants	32.6 Percentage of participants	29.8 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Protein (g/dL)	9.0 Percentage of participants	10.3 Percentage of participants	8.5 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Pseudocholinesterase (U/mL)	11.0 Percentage of participants	11.1 Percentage of participants	8.0 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Sodium (mmol/L)	8.5 Percentage of participants	13.0 Percentage of participants	11.8 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Triacylglycerol Lipase (U/L)	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Urate (mg/dL)	3.6 Percentage of participants	5.0 Percentage of participants	3.8 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Urea (mg/dL)	0.9 Percentage of participants	1.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry eGFR - MDRD Method(mL/min/1.73 m*2)	19.0 Percentage of participants	17.4 Percentage of participants	23.3 Percentage of participants
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry Creatinine Clearance (mL/min)	45.7 Percentage of participants	30.3 Percentage of participants	48.4 Percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to termination visit, up to 10 years

Population: Participants in SAF with evaluable data for each visit

SBP was measured after the participant had been at rest for 10 minutes in a supine position. Low SBP was defined as SBP \<95 mmHg, normal SBP as SBP 95-140mmHg, and high SBP as SBP \>140 mmHg. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=231 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change of Systolic Blood Pressure (SBP) Baseline (Week 0)	114.36 millimetre(s) of mercury (mmHg) Standard Deviation 14.78	113.75 millimetre(s) of mercury (mmHg) Standard Deviation 12.76	110.88 millimetre(s) of mercury (mmHg) Standard Deviation 12.49
Change of Systolic Blood Pressure (SBP) Change from baseline to Termination visit	-0.88 millimetre(s) of mercury (mmHg) Standard Deviation 15.82	-1.30 millimetre(s) of mercury (mmHg) Standard Deviation 15.62	-0.99 millimetre(s) of mercury (mmHg) Standard Deviation 16.12

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to termination visit, up to 10 years

Population: Participants in SAF with evaluable data for each visit

DBP was measured after the participants had been at rest for 10 minutes in a supine position. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=231 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change of Diastolic Blood Pressure (DBP) Baseline (Week 0)	72.03 mmHg Standard Deviation 10.53	71.84 mmHg Standard Deviation 9.06	69.61 mmHg Standard Deviation 9.89
Change of Diastolic Blood Pressure (DBP) Change from baseline to Termination visit	-3.33 mmHg Standard Deviation 12.90	-4.00 mmHg Standard Deviation 11.72	-2.13 mmHg Standard Deviation 9.65

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to termination visit, up to 10 years

Population: Participants in SAF with evaluable data for each visit

Heart rate was measured after the participant had been at rest for 10 minutes in a supine position. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=231 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change of Heart Rate Baseline (Week 0)	76.47 beats/minute (BPM) Standard Deviation 11.04	77.30 beats/minute (BPM) Standard Deviation 12.53	76.04 beats/minute (BPM) Standard Deviation 10.83
Change of Heart Rate Change from baseline to Termination visit	0.75 beats/minute (BPM) Standard Deviation 13.92	0.18 beats/minute (BPM) Standard Deviation 14.07	-1.10 beats/minute (BPM) Standard Deviation 14.74

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to termination visit, up to 10 years

Population: Participants in SAF with evaluable data for each visit

Weight was evaluated for safety. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=231 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change of Weight Baseline (Week 0)	68.24 kilogram (kg) Standard Deviation 18.25	69.03 kilogram (kg) Standard Deviation 16.94	69.57 kilogram (kg) Standard Deviation 14.69
Change of Weight Change from baseline to Termination visit	-1.67 kilogram (kg) Standard Deviation 6.45	0.04 kilogram (kg) Standard Deviation 6.04	-1.79 kilogram (kg) Standard Deviation 8.08

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to termination visit, up to 10 years

Population: Participants in SAF with evaluable data for each visit

SaO2 is one parameters of blood gas. The sample was obtained with the participant resting in a sitting or supine position for at least 10 minutes. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=227 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change of Oxygen Saturation (SaO2) Baseline (Week 0)	95.10 Percentage Standard Deviation 2.61	94.32 Percentage Standard Deviation 3.18	94.00 Percentage Standard Deviation 2.95
Change of Oxygen Saturation (SaO2) Change from baseline to Termination visit	-1.14 Percentage Standard Deviation 3.48	-0.56 Percentage Standard Deviation 4.45	-4.30 Percentage Standard Deviation 5.23

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to termination visit, up to 10 years

Population: Participants in SAF with evaluable data for each visit

PaO2 is one parameter of blood gas. The sample was obtained with the participant resting in a sitting or supine position for at least 10 minutes. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=227 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change of Arterial Partial Oxygen Pressure (PaO2) Baseline (Week 0)	76.99 mmHg Standard Deviation 17.60	74.54 mmHg Standard Deviation 17.84	72.12 mmHg Standard Deviation 13.63
Change of Arterial Partial Oxygen Pressure (PaO2) Change from baseline to Termination visit	-4.77 mmHg Standard Deviation 17.42	7.14 mmHg Standard Deviation 58.00	-8.05 mmHg Standard Deviation 2.76

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to termination visit, up to 10 years

Population: Participants in SAF with evaluable data for each visit

PaCO2 is one parameter of blood gas. The sample was obtained with the participant resting in a sitting or supine position for at least 10 minutes. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=227 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) Baseline (Week 0)	32.94 mmHg Standard Deviation 4.62	32.46 mmHg Standard Deviation 4.63	33.40 mmHg Standard Deviation 4.41
Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) Change from baseline to Termination visit	-1.87 mmHg Standard Deviation 3.72	-0.68 mmHg Standard Deviation 5.70	2.00 mmHg Standard Deviation 4.24

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Month 48

Population: Participants in SAF with evaluable data for each visit

Heart rate from ECG is derived from the RR duration, unless arrhythmias such as atrial fibrillation or ventricular extra beats require additional calculations. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=218 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=103 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=53 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change of RR Duration From Electrocardiogram (ECG) Baseline (Week 0)	817.69 millisecond (msec) Standard Deviation 125.61	828.96 millisecond (msec) Standard Deviation 146.32	822.33 millisecond (msec) Standard Deviation 130.27
Change of RR Duration From Electrocardiogram (ECG) Change from baseline to Month 48	59.07 millisecond (msec) Standard Deviation 109.89	75.69 millisecond (msec) Standard Deviation 181.94	89.61 millisecond (msec) Standard Deviation 113.25

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Month 48

Population: Participants in SAF with evaluable data for each visit

PR duration was evaluated as part of ECG. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=211 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=102 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=53 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change of PR Duration From ECG Baseline (Week 0)	171.07 msec Standard Deviation 27.76	173.97 msec Standard Deviation 32.90	171.74 msec Standard Deviation 25.77
Change of PR Duration From ECG Change from baseline to Month 48	7.51 msec Standard Deviation 16.29	16.50 msec Standard Deviation 19.41	-3.22 msec Standard Deviation 17.18

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Month 48

Population: Participants in SAF with evaluable data for each visit

QRS duration was evaluated as part of ECG. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=213 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=103 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=53 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change of QRS Duration From ECG Change from baseline to Month 48	5.07 msec Standard Deviation 8.56	11.14 msec Standard Deviation 18.69	-0.44 msec Standard Deviation 7.52
Change of QRS Duration From ECG Baseline (Week 0)	99.59 msec Standard Deviation 17.38	100.09 msec Standard Deviation 16.15	103.22 msec Standard Deviation 19.82

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Month 48

Population: Participants in SAF with evaluable data for each visit

QT duration was evaluated as part of ECG. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=177 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=76 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=40 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change of QT Duration in ECG Baseline (Week 0)	401.56 msec Standard Deviation 31.35	406.67 msec Standard Deviation 35.44	405.10 msec Standard Deviation 30.52
Change of QT Duration in ECG Change from baseline to Month 48	10.93 msec Standard Deviation 27.58	16.89 msec Standard Deviation 16.78	27.34 msec Standard Deviation 28.61

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to End of study visit, up to 10 years and 5 months.

6MWD is exercise testing and is one of efficacy evaluation

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=231 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change in Six-minute Walking Distance (6MWD) Test Baseline (Week 0)	375.0 meters Full Range 160 • Interval 160.0 to 468.0	395.0 meters Full Range 174 • Interval 174.0 to 450.0	376.0 meters Full Range 158 • Interval 158.0 to 448.0
Change in Six-minute Walking Distance (6MWD) Test Change from baseline to End of study visit	19.0 meters Full Range -448 • Interval -448.0 to 309.0	9.0 meters Full Range -446 • Interval -446.0 to 275.0	1.5 meters Full Range -448 • Interval -448.0 to 492.0

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Termination visit, up to 10 years 5 months

Population: Participants in SAF with evaluable data for each visit

Pulmonary vascular resistance (PVR) was measured only if right-heart catheterization was performed as part of a regular diagnostic work-up. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=228 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=103 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change in Pulmonary Vascular Resistance (PVR) Baseline (Week 0)	802.40 dynscm^-5 Standard Deviation 452.97	835.45 dynscm^-5 Standard Deviation 476.52	855.70 dynscm^-5 Standard Deviation 552.92
Change in Pulmonary Vascular Resistance (PVR) Change from baseline to Termination visit	34.25 dynscm^-5 Standard Deviation 104.83	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to End of study visit, up to 10 year and 5 months

Population: Participants in SAF with evaluable data for each visit

NT-proBNP levels in the blood are used for diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=210 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=97 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=47 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) Baseline (Week 0)	996.30 picograms/millilitre (pg/mL) Standard Deviation 1627.48	1135.68 picograms/millilitre (pg/mL) Standard Deviation 1533.20	1220.11 picograms/millilitre (pg/mL) Standard Deviation 1457.90
Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) Change from baseline to End of study visit	82.52 picograms/millilitre (pg/mL) Standard Deviation 2253.30	202.42 picograms/millilitre (pg/mL) Standard Deviation 3466.94	115.77 picograms/millilitre (pg/mL) Standard Deviation 1918.81

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to End of study visit, up to 10 years and 5 months.

Population: Participants in SAF with evaluable data for each visit

WHO classification: I: Participants with PH. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope. II: Participants with PH are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope. III: Participants with PH are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. IV: Participants with PH with inability to carry out any physical activity. They manifest signs of right-heart failure. Dyspnea and/or fatigue may even be present at rest. For class change from baseline, minus indicates a participant's functional class decreased compared with baseline (e.g. "-1" indicates a participant changed from class IV to class III, or from class II to class I), plus indicates a participant's functional class increased compared with baseline (e.g. "+1" indicates a participant changed from class I to class II, or from class III to class IV).

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=231 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change in World Health Organization (WHO) Functional Class Baseline (Week 0)-class I	5 Participants	3 Participants	4 Participants
Change in World Health Organization (WHO) Functional Class Baseline (Week 0)-class II	98 Participants	54 Participants	17 Participants
Change in World Health Organization (WHO) Functional Class Baseline (Week 0)-class III	128 Participants	49 Participants	35 Participants
Change in World Health Organization (WHO) Functional Class Baseline (Week 0)-class IV	0 Participants	2 Participants	0 Participants
Change in World Health Organization (WHO) Functional Class Baseline (Week 0)-Missing	0 Participants	1 Participants	0 Participants
Change in World Health Organization (WHO) Functional Class Change from baseline to EOS visit- -2	5 Participants	0 Participants	1 Participants
Change in World Health Organization (WHO) Functional Class Change from baseline to EOS visit- -1	50 Participants	16 Participants	13 Participants
Change in World Health Organization (WHO) Functional Class Change from baseline to EOS visit- 0	101 Participants	52 Participants	28 Participants
Change in World Health Organization (WHO) Functional Class Change from baseline to EOS visit- +1	23 Participants	15 Participants	6 Participants
Change in World Health Organization (WHO) Functional Class Change from baseline to EOS visit- +2	33 Participants	17 Participants	5 Participants
Change in World Health Organization (WHO) Functional Class Change from baseline to EOS visit- +3	19 Participants	8 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to End of study visit, up to 10 years and 5 months.

Time to clinical worsening was a parameter that combined death and events reflective of persistent clinical worsening of the participant's underlying diagnosis of pulmonary hypertension (PH)

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=231 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Number of Participants With Clinical Worsening Decrease in 6MWD due to pulmonary hypertension	7 Participants	6 Participants	2 Participants
Number of Participants With Clinical Worsening Any clinical worsening	87 Participants	41 Participants	18 Participants
Number of Participants With Clinical Worsening Heart/lung transplantation	3 Participants	0 Participants	2 Participants
Number of Participants With Clinical Worsening Atrial septostomy	1 Participants	1 Participants	0 Participants
Number of Participants With Clinical Worsening Hospitalization due to pulmonary hypertension	29 Participants	12 Participants	8 Participants
Number of Participants With Clinical Worsening Start of new pulmonary hypertension treatment	52 Participants	20 Participants	14 Participants
Number of Participants With Clinical Worsening Persistent worsening of functional class due to PH	8 Participants	2 Participants	1 Participants
Number of Participants With Clinical Worsening Death	48 Participants	30 Participants	7 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to End of study visit, up to 10 years and 5 months.

Time to clinical worsening was a parameter that combined death and events reflective of persistent clinical worsening of the participant's underlying diagnosis of pulmonary hypertension (PH)

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=231 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Incidence of Clinical Worsening Events Per 100 Person Years Death	5.49 Percentage per 100 person-years	7.62 Percentage per 100 person-years	3.13 Percentage per 100 person-years
Incidence of Clinical Worsening Events Per 100 Person Years Any clinical worsening event	22.09 Percentage per 100 person-years	22.10 Percentage per 100 person-years	19.20 Percentage per 100 person-years
Incidence of Clinical Worsening Events Per 100 Person Years Heart/Lung Transplantation	0.34 Percentage per 100 person-years	0 Percentage per 100 person-years	0.89 Percentage per 100 person-years
Incidence of Clinical Worsening Events Per 100 Person Years Atrial Septostomy	0.11 Percentage per 100 person-years	0.25 Percentage per 100 person-years	0 Percentage per 100 person-years
Incidence of Clinical Worsening Events Per 100 Person Years Hospitalization due to PH	4.46 Percentage per 100 person-years	3.81 Percentage per 100 person-years	5.80 Percentage per 100 person-years
Incidence of Clinical Worsening Events Per 100 Person Years Start of new PH treatment	9.73 Percentage per 100 person-years	8.13 Percentage per 100 person-years	7.59 Percentage per 100 person-years
Incidence of Clinical Worsening Events Per 100 Person Years Decrease in 6MWD due to PH	1.03 Percentage per 100 person-years	1.78 Percentage per 100 person-years	0.89 Percentage per 100 person-years
Incidence of Clinical Worsening Events Per 100 Person Years Persistent worsening of functional class due to PH	0.92 Percentage per 100 person-years	0.51 Percentage per 100 person-years	0.89 Percentage per 100 person-years

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Week 12

Population: Participants in SAF with evaluable data for each visit

The Borg CR10 Scale was measured in conjunction with the 6MWD test. The test was explained to the participant before starting the 6MWD test. Participants were asked to rank their exertion at the end of the 6MWD test. Low values indicate low levels of exertion; high values indicate more intense exertion reported by the participant. The score ranges from 0 ("Nothing at all") to 10 ("Extremely strong - Maximal")

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=231 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=109 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=56 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change From Baseline in Borg CR 10 Scale Baseline (Week 0)	3.87 Scores on a scale Standard Deviation 2.24	3.80 Scores on a scale Standard Deviation 2.26	3.41 Scores on a scale Standard Deviation 1.77
Change From Baseline in Borg CR 10 Scale Change from baseline to Week 12	-0.58 Scores on a scale Standard Deviation 1.84	-0.54 Scores on a scale Standard Deviation 1.91	-0.52 Scores on a scale Standard Deviation 1.64

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to End of study visit, up to 10 years and 5 months.

Population: Participants in SAF with evaluable data for each visit

The EQ-5D is a standardized instrument for use as a measure of health outcome. The EQ-5D is a self report questionnaire. The utility score is calculated based on five questions concerning problems with mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the utility score represents an improvement in quality of life. The score ranges from -0.594 (worst answer in all five questions) to 1 (best answer in all five questions).

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=230 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=107 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=55 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change in Score of EQ-5D Questionnaire Baseline (Week 0)	0.6883 Scores on a scale Standard Deviation 0.2339	0.6929 Scores on a scale Standard Deviation 0.2302	0.6338 Scores on a scale Standard Deviation 0.2744
Change in Score of EQ-5D Questionnaire Change from baseline to EOS Visit	-0.2452 Scores on a scale Standard Deviation 0.5894	-0.2812 Scores on a scale Standard Deviation 0.5944	-0.0925 Scores on a scale Standard Deviation 0.4376

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to End of study visit, up to 10 years and 5 months.

Population: Participants in SAF with evaluable data for each visit

The LPH questionnaire is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The LPH is a self-report questionnaire and was completed by the participant. The LPH total score can range from 0 (best) to 105 (worst).

Outcome measures

Outcome measures
Measure	Riociguat-Former Riociguat 1.0-2.5 mg n=225 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.	Riociguat-Former Placebo n=105 Participants Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day.	Riociguat-Former Riociguat 1.0-1.5 mg n=55 Participants Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1.
Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire Baseline (Week 0)	41.77 Scores on a scale Standard Deviation 22.18	41.94 Scores on a scale Standard Deviation 23.34	45.10 Scores on a scale Standard Deviation 22.08
Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire Change from baseline to EOS Visit	4.99 Scores on a scale Standard Deviation 34.04	12.28 Scores on a scale Standard Deviation 32.76	-4.07 Scores on a scale Standard Deviation 31.40

Adverse Events

Former Riociguat 1.0- 2.5 mg

Serious events: 161 serious events

Other events: 218 other events

Deaths: 48 deaths

Former Riociguat 1.0 - 1.5 mg

Serious events: 39 serious events

Other events: 54 other events

Deaths: 7 deaths

Former Placebo

Serious events: 76 serious events

Other events: 106 other events

Deaths: 30 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head

Bayer AG

Phone: (+) 1-888-8422937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER