Global Amendment 1: Version 2.0 is considered to be the initial version of the CTP and included some modifications after version 1.0 has been archived. The original version 1.0 of this protocol was not submitted to any authorities, ethics committees or institutional review board for approval of the clinical trial.

Global Amendment 2: -The column header “Post dose” and a cross to indicate post dose ECG at Visit 3 were added to the flow chart.-Extended the maximum time before randomisation from 28 to 35 days throughout the protocol.-Further requirement to inclusion criterion #3 was added: eGFR must remain ≥20 mL/min/1.73 m2 after Visit 1 up to the start of Visit 3, measured by central or any local laboratory analysis.-Adverse events to be summarized by the treatment to which the subject was randomised, and the treatment at the onset of AE for the drug-related AE rather than the treatment at end of the up-titration period as was before.

Global Amendment 3: Addition of ECGs at visits where there were previously no ECGs: three ECGs at visits 4, 5 and one ECG at Visits 7 and 8. At Visits 3 and 6 an additional ECG to be done to the two already performed. -eGFR has been added as a test that patients can be pre-screened for if consent is given.Potential QT-interval prolongation was added as a risk along with the summary of data, rationale for the risk and the mitigation strategy.-Exclusion criteria 11) Removal of lactose monohydrate as an example of an excipient.Addition of the following exclusion criteria:17. QTcF -interval >450 ms in men or >470 ms in women at any time from screening (Visit 1) until start of treatment. 18. A family history of long QT syndrome. 19. Concomitant use of therapies with a known risk of Torsade de Pointes at screening (Visit 1) and throughout screening and baseline run-in or planned initiation of such therapies during the trial.The following was added to Discontinuation of Trial Treatment: Patients with a QT or QTcF interval >500 ms, or an increase of QT or QTcF of >60 ms from the pre-dosevalue at Visit 3 (baseline). Such cases must be reported as AEs.-Text was added to state that ECGs were to be performed prior to blood draws and after the patient has been in the supine position for 5 min.

Global Amendment 4: Exclusion criterion #1 was changed to: Treatment with Renin Angiotensin Aldosterone System (RAAS) interventions (apart from either ACEi or ARB), phosphodiesterase-5 inhibitors, non-specific phosphodiesterase inhibitors (such as dipyridamole and theophylline), NO donors including nitrates, sGCstimulators/activators (other than trial treatment) or any other restricted medication (including OATP1B1/3 inhibitors, UGT inhibitors/inducers) as provided in the Investigator Site File (ISF) within 4 weeks prior to Visit 1 and throughout screening and baseline run-in. Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial are also excluded.

Global Amendment 4: Patients who must or wish to continue the intake of restricted medications (see section 4.2.2.1) or any drug considered likely to interfere with the safe conduct of the trial are also excluded. 3.3.4.1 Discontinuation of trial treatment: The patient experiences a severe infection e.g. with SARSCoV- 2, as determined by the Investigator. Was changed to: The patient experiences a severe infection, e.g. with SARSCoV-2 that precludes their safe participation in the trial, as determined by the Investigator. 4.2.2.1 Restrictions regarding concomitant treatment: Phosphodiesterase inhibitors Nitrates in table 4.2.2.1:1 replaced with: Phosphodiesterase-5 inhibitors, non-specific phosphodiesterase inhibitors (such as dipyridamole and theophylline). 7.2.1: The TS is used for safety analyses as well as demographics and baseline characteristics. was replaced with: The TS is used for safety analyses and exposure.