BAY63-2521:Long-term Extension Study in Patients With Pulmonary Arterial Hypertension (PATENT-2)

Long-term Extension, Multicentre, Multi-national Study to Evaluate the Safety and Tolerability of Oral BAY63-2521 (1mg,1.5 mg, 2.0 mg, 2.5 mg Tid) in Patients With Symptomatic Pulmonary Arterial Hypertension (PAH)

Patients who have completed the 12 weeks treatment of the PATENT-1 trial (study number 12934) will be asked to participate in this long term extension study with BAY63-2521.

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

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 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.

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

Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation

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.

Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation

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.

Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry

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.

Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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).

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)

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)

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")

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).

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).

Inclusion Criteria: Patients who have completed 12 weeks of treatment in the double blind trial PATENT 1 Exclusion Criteria: Patients who have an ongoing serious adverse event from PATENT 1 that is assessed as related to BAY63-2521 are not allowed to participate in the extension trial.

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