Chronic Kidney Disease
Conditions
Brief summary
This study is open to adults who have kidney disease that is not caused by diabetes. The purpose of the study is to find out whether a medicine called avenciguat (BI 685509) improves kidney function. Three different doses of avenciguat are tested in this study. Participants get either one of the three doses of avenciguat or placebo. It is decided by chance who gets which avenciguat dose and who gets placebo. Participants take avenciguat or placebo as tablets 3 times a day. Placebo tablets look like avenciguat tablets but do not contain any medicine. Participants continue taking their usual medicine for kidney disease throughout the study. Participants are in the study for about 7 months. During this time, they visit the study site about 11 times. Where possible, about 6 of the 11 visits can be done at the participant's home instead of the study site. The trial staff may also contact the participants by phone or video call. Kidney function is assessed based on the analysis of urine samples, which participants collect at home. At the end of the trial the results are compared between the different doses of avenciguat and placebo. During the study, the doctors also regularly check the general health of the participants.
Interventions
DRUGAvenciguat
Avenciguat
DRUGPlacebo
Placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated written informed consent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial. * Male or female patients aged ≥18 years at time of consent. * Estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula) ≥ 20 and \< 90 mL/min/1.73 m2 at Visit 1 by central laboratory analysis. 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. * Urine albumin creatinine ratio (UACR) ≥ 200 and \< 3,500 mg/g in spot urine (midstream urine sample) by central laboratory analysis at Visit 1. * Patients with macroalbuminuria (\>300 mg/g) should be treated with the highest tolerated dose of either Angiotensin Converting Enzyme inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) (but not both). For patients with microalbuminuria the use of ACEi or ARB is at the discretion of the Investigator. Treatment should be at a stable dose for ≥ 4 weeks before Visit 1 with no planned change of the therapy during the trial. * If the patient is taking any of the following medications they should be on a stable dose at least 4 weeks prior to visit 1 until start of treatment, with no planned change of the therapy during the trial: anti-hypertensives, non-steroidal anti-inflammatory drugs (NSAIDs), endothelin receptor antagonists, systemic steroids or Sodium-glucose co-transporter-2 (SGLT2) inhibitors. * In the Investigator's judgment any kind of diagnosed chronic kidney disease whose primary cause is clinically not considered to be of diabetic origin. Further inclusion criteria apply
Exclusion criteria
* 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), Nitric Oxide (NO) donors including nitrates, soluble Guanylate Cyclase (sGC)-stimulators/activators (other than trial treatment) or any other restricted medication (including Organic Anion-Transporting Polypeptide 1B1 and 1B3 (OATP1B1/3) inhibitors, Uridine 5'-diphosphate -glucuronosyltransferase (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. * Any clinically relevant laboratory value from screening until start of trial treatment which, in the investigator's judgement, puts the patient at additional risk. * Diagnosed with diabetic kidney disease. * Any immunosuppression therapy or immunotherapy in last 3 months prior to visit 1 and throughout screening and baseline run-in (except prednisolone ≤10 mg or equivalent). * Acute kidney injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition in the 30 days prior to Visit 1 until the start of trial treatment. * Planned start of chronic renal replacement therapy during the trial or end stage renal disease before start of trial treatment. * Known history of moderate or severe symptomatic orthostatic dysregulation as judged by the investigator before start of trial treatment. * The patient has an active infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (or is known to have a positive test from screening until randomisation). * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Log Transformed UACR Measured in First Morning Void Urine After 20 Weeks of Trial Treatment | 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. | 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. |
| Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | At baseline (Day -14 and Day -7) and at Week 20 (Day 141) after start of trial treatment. | 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. |
| Number of Patients Achieving UACR Decreases in First Morning Void Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | At baseline (Day -14 and Day -7) and at Week 20 (Day 141) after start of trial treatment. | 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. |
Countries
Argentina, Australia, Canada, China, Denmark, Germany, Hong Kong, Japan, Malaysia, Mexico, New Zealand, Poland, Portugal, Russia, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 64 |
| 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. | 65 |
| 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. | 66 |
| 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. | 66 |
| Total | 261 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 4 | 3 |
| Overall Study | Burden of study procedures | 1 | 0 | 0 | 1 |
| Overall Study | Change of residence | 0 | 1 | 0 | 0 |
| Overall Study | Not treated | 0 | 0 | 0 | 2 |
| Overall Study | Other reason than listed | 1 | 2 | 2 | 3 |
| Overall Study | Perceived lack of efficacy | 1 | 0 | 0 | 1 |
| Overall Study | Protocol deviation | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Avenciguat 2 mg TID | Total | Placebo | Avenciguat 1 mg TID | Avenciguat 3 mg TID |
|---|---|---|---|---|---|
| Age, Continuous | 60.4 Years STANDARD_DEVIATION 15.5 | 58.1 Years STANDARD_DEVIATION 15.4 | 58.1 Years STANDARD_DEVIATION 14.4 | 54.6 Years STANDARD_DEVIATION 16.3 | 59.3 Years STANDARD_DEVIATION 15 |
| Baseline urine albumine creatinine ratio (UACR), 10-hour urine | 868.2 milligram/gram STANDARD_DEVIATION 727.7 | 977.6 milligram/gram STANDARD_DEVIATION 1213.7 | 1076.2 milligram/gram STANDARD_DEVIATION 1786.2 | 1024.1 milligram/gram STANDARD_DEVIATION 920.1 | 941.5 milligram/gram STANDARD_DEVIATION 1155.2 |
| Baseline Urine Albumine Creatinine Ratio (UACR) in First Morning Void (FMV) | 745.4 milligram/gram STANDARD_DEVIATION 661.9 | 829.9 milligram/gram STANDARD_DEVIATION 949.5 | 874.1 milligram/gram STANDARD_DEVIATION 1142 | 879.1 milligram/gram STANDARD_DEVIATION 840.8 | 821.3 milligram/gram STANDARD_DEVIATION 1083.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 67 Participants | 18 Participants | 18 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 194 Participants | 48 Participants | 46 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 12 Participants | 4 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 65 Participants | 15 Participants | 18 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 17 Participants | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 38 Participants | 159 Participants | 40 Participants | 39 Participants | 42 Participants |
| Sex: Female, Male Female | 16 Participants | 80 Participants | 17 Participants | 21 Participants | 26 Participants |
| Sex: Female, Male Male | 49 Participants | 181 Participants | 49 Participants | 43 Participants | 40 Participants |
| Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use at randomization No | 51 Participants | 199 Participants | 50 Participants | 47 Participants | 51 Participants |
| Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use at randomization Yes | 14 Participants | 62 Participants | 16 Participants | 17 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 65 | 0 / 66 | 0 / 64 |
| other Total, other adverse events | 17 / 64 | 19 / 65 | 26 / 66 | 21 / 64 |
| serious Total, serious adverse events | 3 / 64 | 3 / 65 | 6 / 66 | 6 / 64 |
Outcome results
Primary
Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Avenciguat 1 mg TID | 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 |
| Avenciguat 2 mg TID | Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment | -0.190 log (mg/g) | Standard Error 0.068 |
| Avenciguat 3 mg TID | Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment | -0.217 log (mg/g) | Standard Error 0.068 |
| Placebo | Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment | 0.018 log (mg/g) | Standard Error 0.068 |
Comparison: Least Squares Mean differences and 95% confidence intervals 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.p-value: 0.017995% CI: [-0.417, -0.04]Mixed-effect Model repeat Measurement
Comparison: Least Squares Mean differences and 95% confidence intervals 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.p-value: 0.030795% CI: [-0.398, -0.02]Mixed-effect Model repeat Measurement
Comparison: Least Squares Mean differences and 95% confidence intervals 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.p-value: 0.015195% CI: [-0.425, -0.046]Mixed-effect Model repeat Measurement
Comparison: A flat vs. non-flat dose-response relationship across the 3 doses of avenciguat and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (Emax, exponential, linear, quadratic, sigmoid emax) while protecting the overall probability of type I error (one-sided alpha of 0.050).~The total daily dose was considered for MCP-Mod analysis (placebo, active avenciguat 3 mg, 6 mg, and 9 mg).p-value: 0.0053MCP-Mod E-max model fit
Comparison: A flat vs. non-flat dose-response relationship across the 3 doses of avenciguat and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (Emax, exponential, linear, quadratic, sigmoid emax) while protecting the overall probability of type I error (one-sided alpha of 0.050).~The total daily dose was considered for MCP-Mod analysis (placebo, active avenciguat 3 mg, 6 mg, and 9 mg).p-value: 0.0102MCP-Mod quadratic model fit
Comparison: A flat vs. non-flat dose-response relationship across the 3 doses of avenciguat and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (Emax, exponential, linear, quadratic, sigmoid emax) while protecting the overall probability of type I error (one-sided alpha of 0.050).~The total daily dose was considered for MCP-Mod analysis (placebo, active avenciguat 3 mg, 6 mg, and 9 mg).p-value: 0.023MCP-Mod linear model fit
Comparison: A flat vs. non-flat dose-response relationship across the 3 doses of avenciguat and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (Emax, exponential, linear, quadratic, sigmoid emax) while protecting the overall probability of type I error (one-sided alpha of 0.050).~The total daily dose was considered for MCP-Mod analysis (placebo, active avenciguat 3 mg, 6 mg, and 9 mg).p-value: 0.0292MCP-Mod Sigmoid Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 3 doses of avenciguat and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (Emax, exponential, linear, quadratic, sigmoid emax) while protecting the overall probability of type I error (one-sided alpha of 0.050).~The total daily dose was considered for MCP-Mod analysis (placebo, active avenciguat 3 mg, 6 mg, and 9 mg).p-value: 0.0468MCP-Mod Exponential model fit
Secondary
Change From Baseline in Log Transformed UACR Measured in First Morning Void Urine After 20 Weeks of Trial Treatment
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Avenciguat 1 mg TID | 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 |
| Avenciguat 2 mg TID | Change From Baseline in Log Transformed UACR Measured in First Morning Void Urine After 20 Weeks of Trial Treatment | -0.180 log (mg/g) | Standard Error 0.073 |
| Avenciguat 3 mg TID | Change From Baseline in Log Transformed UACR Measured in First Morning Void Urine After 20 Weeks of Trial Treatment | -0.161 log (mg/g) | Standard Error 0.071 |
| Placebo | Change From Baseline in Log Transformed UACR Measured in First Morning Void Urine After 20 Weeks of Trial Treatment | 0.027 log (mg/g) | Standard Error 0.072 |
Comparison: Least Squares Mean differences and 95% confidence intervals 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.p-value: 0.032795% CI: [-0.416, -0.018]Mixed-effect Model repeat Measurement
Comparison: Least Squares Mean differences and 95% confidence intervals 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.p-value: 0.044795% CI: [-0.408, -0.005]Mixed-effect Model repeat Measurement
Comparison: Least Squares Mean differences and 95% confidence intervals 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.p-value: 0.065495% CI: [-0.387, 0.012]Mixed-effect Model repeat Measurement
Secondary
Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Avenciguat 1 mg TID | Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | 25 Participants |
| Avenciguat 2 mg TID | Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | 27 Participants |
| Avenciguat 3 mg TID | Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | 31 Participants |
| Placebo | Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | 14 Participants |
Comparison: Treatment and sodium-glucose co-transporter-2 inhibitor (SGLT2i) use at randomization were used as covariates in the logistic regression model.p-value: 0.047695% CI: [1.01, 4.79]Regression, Logistic
Comparison: Treatment and sodium-glucose co-transporter-2 inhibitor (SGLT2i) use at randomization were used as covariates in the logistic regression model.p-value: 0.011995% CI: [1.25, 5.94]Regression, Logistic
Comparison: Treatment and sodium-glucose co-transporter-2 inhibitor (SGLT2i) use at randomization were used as covariates in the logistic regression model.p-value: 0.001995% CI: [1.58, 7.45]Regression, Logistic
Secondary
Number of Patients Achieving UACR Decreases in First Morning Void Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Avenciguat 1 mg TID | 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 |
| Avenciguat 2 mg TID | Number of Patients Achieving UACR Decreases in First Morning Void Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | 26 Participants |
| Avenciguat 3 mg TID | Number of Patients Achieving UACR Decreases in First Morning Void Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | 26 Participants |
| Placebo | Number of Patients Achieving UACR Decreases in First Morning Void Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | 16 Participants |
Comparison: Treatment and sodium-glucose co-transporter-2 inhibitor (SGLT2i) use at randomization were used as covariates in the logistic regression model.p-value: 0.049795% CI: [1, 4.55]Regression, Logistic
Comparison: Treatment and sodium-glucose co-transporter-2 inhibitor (SGLT2i) use at randomization were used as covariates in the logistic regression model.p-value: 0.050295% CI: [1, 4.61]Regression, Logistic
Comparison: Treatment and sodium-glucose co-transporter-2 inhibitor (SGLT2i) use at randomization were used as covariates in the logistic regression model.p-value: 0.057295% CI: [0.98, 4.49]Regression, Logistic