Trial Outcomes & Findings for A Study to Test the Effect of Different Doses of Avenciguat (BI 685509) on Kidney Function in People With Chronic Kidney Disease (NCT NCT04736628)

Last Updated: 2024-09-04

Results Overview

Change from baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in 10-hour urine after 20 weeks of trial treatment is reported. Least Squares Mean (Standard error) were estimated by restricted maximum likelihood (REML)-based mixed-effect model for repeated measures (MMRM) including the fixed, categorical effects of treatment at each visit (baseline, Week 6, Week 12, and Week 20), and the continuous effect of baseline at each visit (Week 6, Week 12, and Week 20) as well as random effects of patient. Log transformed UACR at Week 20 was log of (average of all available scheduled measurements between week 18 and week 20). The data in the Outcome Measure Data Table represent the Least Squares Mean (Standard error) at Week 20.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

261 participants

Primary outcome timeframe

The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week -2, Week -1, Week 0 pre-dose) and Week 6, Week 12 and Week 20. The data represent the Least Squares Mean at Week 20.

Results posted on

2024-09-04

Participant Flow

This trial was a Phase II, randomised, placebo-controlled, double-blind (within dose groups), parallel, multicentre clinical trial in patients with non-diabetic kidney disease (non-DKD) to demonstrate the effectiveness and safety of avenciguat and to characterize the dose-response relationship for avenciguat in patients with non-DKD by assessing 3 doses and placebo.

Patients underwent a screening period of up to 3 weeks from the time of informed consent. After confirmation of eligibility at screening, patients continued in a 2-week baseline run-in period. Patients who successfully completed the screening and baseline run-in periods and met the inclusion/exclusion criteria were randomised equally into 1 of 3 parallel dose groups, and in each dose group to treatment either with avenciguat or matching placebo in a 3:1 ratio.

Participant milestones

Participant milestones
Measure	Avenciguat 1 mg TID Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 2 mg TID Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 3 mg TID Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 4 of treatment. Then if medication was tolerated, up-titration to 3 mg avenciguat (one film-coated tablet of 3 mg) TID occurred from Week 5 until Week 20. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Placebo This arm comprises all placebo treated participants. Participants were administered film-coated tablets of placebo matching avenciguat 1mg, 2mg or 3mg 3 times a day (TID) during 20 weeks of treatment. Placebo matching avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
Overall Study STARTED	64	65	66	66
Overall Study Treated	64	65	66	64
Overall Study COMPLETED	58	60	60	55
Overall Study NOT COMPLETED	6	5	6	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Avenciguat 1 mg TID Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 2 mg TID Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 3 mg TID Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 4 of treatment. Then if medication was tolerated, up-titration to 3 mg avenciguat (one film-coated tablet of 3 mg) TID occurred from Week 5 until Week 20. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Placebo This arm comprises all placebo treated participants. Participants were administered film-coated tablets of placebo matching avenciguat 1mg, 2mg or 3mg 3 times a day (TID) during 20 weeks of treatment. Placebo matching avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
Overall Study Not treated	0	0	0	2
Overall Study Other reason than listed	1	2	2	3
Overall Study Protocol deviation	0	0	0	1
Overall Study Burden of study procedures	1	0	0	1
Overall Study Change of residence	0	1	0	0
Overall Study Perceived lack of efficacy	1	0	0	1
Overall Study Adverse Event	3	2	4	3

Baseline Characteristics

A Study to Test the Effect of Different Doses of Avenciguat (BI 685509) on Kidney Function in People With Chronic Kidney Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Avenciguat 1 mg TID n=64 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 2 mg TID n=65 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 3 mg TID n=66 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 4 of treatment. Then if medication was tolerated, up-titration to 3 mg avenciguat (one film-coated tablet of 3 mg) TID occurred from Week 5 until Week 20. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Placebo n=66 Participants This arm comprises all placebo treated participants. Participants were administered film-coated tablets of placebo matching avenciguat 1mg, 2mg or 3mg 3 times a day (TID) during 20 weeks of treatment. Placebo matching avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Total n=261 Participants Total of all reporting groups
Age, Continuous	54.6 Years STANDARD_DEVIATION 16.3 • n=5 Participants	60.4 Years STANDARD_DEVIATION 15.5 • n=7 Participants	59.3 Years STANDARD_DEVIATION 15.0 • n=5 Participants	58.1 Years STANDARD_DEVIATION 14.4 • n=4 Participants	58.1 Years STANDARD_DEVIATION 15.4 • n=21 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	16 Participants n=7 Participants	26 Participants n=5 Participants	17 Participants n=4 Participants	80 Participants n=21 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	49 Participants n=7 Participants	40 Participants n=5 Participants	49 Participants n=4 Participants	181 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	20 Participants n=7 Participants	11 Participants n=5 Participants	18 Participants n=4 Participants	67 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	46 Participants n=5 Participants	45 Participants n=7 Participants	55 Participants n=5 Participants	48 Participants n=4 Participants	194 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	12 Participants n=21 Participants
Race (NIH/OMB) Asian	18 Participants n=5 Participants	20 Participants n=7 Participants	12 Participants n=5 Participants	15 Participants n=4 Participants	65 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants	5 Participants n=4 Participants	17 Participants n=21 Participants
Race (NIH/OMB) White	39 Participants n=5 Participants	38 Participants n=7 Participants	42 Participants n=5 Participants	40 Participants n=4 Participants	159 Participants n=21 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use at randomization Yes	17 Participants n=5 Participants	14 Participants n=7 Participants	15 Participants n=5 Participants	16 Participants n=4 Participants	62 Participants n=21 Participants
Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use at randomization No	47 Participants n=5 Participants	51 Participants n=7 Participants	51 Participants n=5 Participants	50 Participants n=4 Participants	199 Participants n=21 Participants
Baseline urine albumine creatinine ratio (UACR), 10-hour urine	1024.1 milligram/gram STANDARD_DEVIATION 920.1 • n=5 Participants	868.2 milligram/gram STANDARD_DEVIATION 727.7 • n=7 Participants	941.5 milligram/gram STANDARD_DEVIATION 1155.2 • n=5 Participants	1076.2 milligram/gram STANDARD_DEVIATION 1786.2 • n=4 Participants	977.6 milligram/gram STANDARD_DEVIATION 1213.7 • n=21 Participants
Baseline Urine Albumine Creatinine Ratio (UACR) in First Morning Void (FMV)	879.1 milligram/gram STANDARD_DEVIATION 840.8 • n=5 Participants	745.4 milligram/gram STANDARD_DEVIATION 661.9 • n=7 Participants	821.3 milligram/gram STANDARD_DEVIATION 1083.5 • n=5 Participants	874.1 milligram/gram STANDARD_DEVIATION 1142.0 • n=4 Participants	829.9 milligram/gram STANDARD_DEVIATION 949.5 • n=21 Participants

PRIMARY outcome

Timeframe: The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week -2, Week -1, Week 0 pre-dose) and Week 6, Week 12 and Week 20. The data represent the Least Squares Mean at Week 20.

Population: Full Analysis Set (FAS): included all patients who had at least one baseline measurement of UACR in Week -2, -1, or 0 and at least 1 post-baseline measurement after Week 6.

Outcome measures

Outcome measures
Measure	Avenciguat 1 mg TID n=64 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 2 mg TID n=61 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 3 mg TID n=62 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 4 of treatment. Then if medication was tolerated, up-titration to 3 mg avenciguat (one film-coated tablet of 3 mg) TID occurred from Week 5 until Week 20. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Placebo n=62 Participants This arm comprises all placebo treated participants. Participants were administered film-coated tablets of placebo matching avenciguat 1mg, 2mg or 3mg 3 times a day (TID) during 20 weeks of treatment. Placebo matching avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment	-0.210 log (mg/g) Standard Error 0.067	-0.190 log (mg/g) Standard Error 0.068	-0.217 log (mg/g) Standard Error 0.068	0.018 log (mg/g) Standard Error 0.068

SECONDARY outcome

Timeframe: The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week -2 and Week -1) and Week 6, Week 12 and Week 20. The data represent the Least Squares Mean at Week 20.

Population: Full Analysis Set (FAS): included all patients who had at least one baseline measurement of UACR in Week -2, -1, or 0 and at least 1 post-baseline measurement after Week 6.

Change from baseline in log transformed UACR measured in First Morning Void urine after 20 weeks of trial treatment is reported. Least Squares Mean (Standard error) were estimated by restricted maximum likelihood (REML)-based mixed-effect model for repeated measures (MMRM) including the fixed, categorical effects of treatment at each visit (baseline, Week 6, Week 12 and Week 20), and the continuous effect of baseline at each visit (Week 6, Week 12, and Week 20) as well as random effects of patient. The first morning void (FMV) was the first urination after the patient woke up at their usual time to start their day. Log transformed UACR at Week 20 was log of (average of all available scheduled measurements between week 18 and week 20). The data in the Outcome Measure Data Table represent the Least Squares Mean (Standard error) at Week 20.

Outcome measures

Outcome measures
Measure	Avenciguat 1 mg TID n=64 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 2 mg TID n=61 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 3 mg TID n=62 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 4 of treatment. Then if medication was tolerated, up-titration to 3 mg avenciguat (one film-coated tablet of 3 mg) TID occurred from Week 5 until Week 20. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Placebo n=62 Participants This arm comprises all placebo treated participants. Participants were administered film-coated tablets of placebo matching avenciguat 1mg, 2mg or 3mg 3 times a day (TID) during 20 weeks of treatment. Placebo matching avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
Change From Baseline in Log Transformed UACR Measured in First Morning Void Urine After 20 Weeks of Trial Treatment	-0.190 log (mg/g) Standard Error 0.071	-0.180 log (mg/g) Standard Error 0.073	-0.161 log (mg/g) Standard Error 0.071	0.027 log (mg/g) Standard Error 0.072

SECONDARY outcome

Timeframe: At baseline (Day -14 and Day -7) and at Week 20 (Day 141) after start of trial treatment.

Population: Full Analysis Set (FAS): included all patients who had at least one baseline measurement of UACR in Week -2, -1, or 0 and at least 1 post-baseline measurement after Week 6.

Number of patients achieving urine albumin creatinine ratio (UACR) decreases in 10-hour urine of at least 20% from baseline after 20 weeks of trial treatment. During the 10-hour period every time the patient urinates, and the patient collected their urine into a provided container. An aliquot of this urine was taken and used as the 10-hour UACR sample.

Outcome measures

Outcome measures
Measure	Avenciguat 1 mg TID n=64 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 2 mg TID n=61 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 3 mg TID n=62 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 4 of treatment. Then if medication was tolerated, up-titration to 3 mg avenciguat (one film-coated tablet of 3 mg) TID occurred from Week 5 until Week 20. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Placebo n=62 Participants This arm comprises all placebo treated participants. Participants were administered film-coated tablets of placebo matching avenciguat 1mg, 2mg or 3mg 3 times a day (TID) during 20 weeks of treatment. Placebo matching avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment	25 Participants	27 Participants	31 Participants	14 Participants

SECONDARY outcome

Timeframe: At baseline (Day -14 and Day -7) and at Week 20 (Day 141) after start of trial treatment.

Population: Full Analysis Set (FAS): included all patients who had at least one baseline measurement of UACR in Week -2, -1, or 0 and at least 1 post-baseline measurement after Week 6.

Number of patients achieving urine albumin creatinine ratio (UACR) decreases in First Morning Void urine of at least 20% from baseline after 20 weeks of trial treatment is reported. The first morning void (FMV) was the first urination after the patient woke up at their usual time to start their day.

Outcome measures

Outcome measures
Measure	Avenciguat 1 mg TID n=64 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 2 mg TID n=61 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 3 mg TID n=62 Participants Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 4 of treatment. Then if medication was tolerated, up-titration to 3 mg avenciguat (one film-coated tablet of 3 mg) TID occurred from Week 5 until Week 20. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Placebo n=62 Participants This arm comprises all placebo treated participants. Participants were administered film-coated tablets of placebo matching avenciguat 1mg, 2mg or 3mg 3 times a day (TID) during 20 weeks of treatment. Placebo matching avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
Number of Patients Achieving UACR Decreases in First Morning Void Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment	27 Participants	26 Participants	26 Participants	16 Participants

Adverse Events

Avenciguat 1 mg TID

Serious events: 3 serious events

Other events: 17 other events

Deaths: 0 deaths

Avenciguat 2 mg TID

Serious events: 3 serious events

Other events: 19 other events

Deaths: 0 deaths

Avenciguat 3 mg TID

Serious events: 6 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Avenciguat 1 mg TID n=64 participants at risk Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 2 mg TID n=65 participants at risk Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Avenciguat 3 mg TID n=66 participants at risk Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 4 of treatment. Then if medication was tolerated, up-titration to 3 mg avenciguat (one film-coated tablet of 3 mg) TID occurred from Week 5 until Week 20. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	Placebo n=64 participants at risk This arm comprises all placebo treated participants. Participants were administered film-coated tablets of placebo matching avenciguat 1mg, 2mg or 3mg 3 times a day (TID) during 20 weeks of treatment. Placebo matching avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
Gastrointestinal disorders Diarrhoea	3.1% 2/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	4.6% 3/65 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	9.1% 6/66 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	6.2% 4/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.
Gastrointestinal disorders Nausea	3.1% 2/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	0.00% 0/65 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	6.1% 4/66 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	1.6% 1/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.
General disorders Fatigue	0.00% 0/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	3.1% 2/65 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	9.1% 6/66 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	3.1% 2/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.
General disorders Oedema peripheral	0.00% 0/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	6.2% 4/65 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	7.6% 5/66 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	7.8% 5/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.
Infections and infestations COVID-19	6.2% 4/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	7.7% 5/65 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	4.5% 3/66 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	6.2% 4/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.
Infections and infestations Nasopharyngitis	6.2% 4/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	3.1% 2/65 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	4.5% 3/66 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	3.1% 2/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.
Metabolism and nutrition disorders Gout	1.6% 1/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	4.6% 3/65 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	7.6% 5/66 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	0.00% 0/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.
Nervous system disorders Headache	7.8% 5/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	1.5% 1/65 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	7.6% 5/66 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	4.7% 3/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.
Vascular disorders Hypotension	4.7% 3/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	9.2% 6/65 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	7.6% 5/66 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.	4.7% 3/64 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first avenciguat intake until last avenciguat intake or patient's trial termination date, whichever occurs earlier + 7 days of Residual effect period (REP), up to 148 days. Treated Set (TS): this patient set included all patients who received at least 1 dose of trial medication.

Additional Information

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