Diabetic Nephropathies
Conditions
Brief summary
This study is open to adults with diabetic kidney disease. The purpose of the study is to find out whether a medicine called BI 685509 improves kidney function. Three different doses of BI 685509 are tested in this study. Participants get either one of the three doses of BI 685509 or placebo. It is decided by chance who gets which BI 685509 dose and who gets placebo. Participants take BI 685509 or placebo as tablets 3 times a day. Placebo tablets look like BI 685509 tablets but do not contain any medicine. Participants continue taking their usual medicine for diabetes and 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 BI 685509 and placebo. During the study, the doctors also regularly check the general health of the participants.
Interventions
DRUGPlacebo matching BI 685509
film-coated tablet
DRUGBI 685509
film-coated tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Multicentre, randomised, double-blind (within dose groups), parallel, placebo-controlled trial. Patients will be randomised equally into one of three parallel dose groups, and in each dose group to treatment either with BI 685509 or matching placebo in a 3:1 ratio.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed and dated written informed consent in accordance with International Council of Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial. 2. Male or female patients aged ≥ 18 years at time of consent. 3. 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. 4. Urine Albumin Creatinine Ratio (UACR) ≥ 200 and \< 3,500 mg/g in spot urine (midstream urine sample) by central laboratory analysis at Visit 1. 5. Treatment with the highest tolerated dose of either Angiotensin Converting Enzyme inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) (but not both together), and stable dose for ≥ 4 weeks before Visit 1 with no planned change of the therapy during the trial. 6. 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 drug(s) (NSAIDs), endothelin receptor antagonists, systemic steroids or Sodium-Glucose co-Transporter-2 (SGLT2) inhibitors. 7. Patients with stable type 1 or type 2 diabetes mellitus, diagnosed before informed consent. Treatment (including SGLT2 inhibitor and/or Glucagon-Like Peptide 1 (GLP1) receptor agonist) should have been unchanged or changes deemed minor (according to investigator's judgement) within 4 weeks before Visit 1 and until start of trial treatment. 8. Glycated Haemoglobin (HbA1c) \< 10.0% at Visit 1 measured by the central laboratory. Further inclusion criteria apply.
Exclusion criteria
1. 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, sGC-stimulators/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. 2. Any clinically relevant laboratory value from screening until start of trial treatment, which in the investigator's judgement puts the patient at additional risk. 3. Biopsy or otherwise confirmed non-diabetic chronic kidney disease, or non-diabetic chronic kidney disease in the opinion of investigator, e.g., Autosomal Dominant Polycystic Kidney Disease (ADPKD), uncontrolled lupus nephritis. The presence of a hypertensive etiology does not need to be excluded unless it is evident this is the only cause for the Chronic Kidney Disease (CKD). 4. Any immunosuppression therapy or immunotherapy in the last 3 months prior to visit 1 and throughout screening and baseline run-in (except prednisolone ≤10 mg or equivalent). 5. Acute kidney injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) in the 30 days prior to Visit 1 until the start of trial treatment. 6. Planned start of chronic renal replacement therapy during the trial or end stage renal disease before start of trial treatment. 7. Known history of moderate or severe symptomatic orthostatic dysregulation as judged by the investigator before start of trial treatment. 8. 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 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 Urine Albumin Creatinine Ratio (UACR) after 20 weeks is reported. As soon as the First Morning Void sample was collected the clock starts for the 10-hour urine collection. During the 10-hour period every time the patient urinates, they collected their urine into a provided container. An aliquot of this urine was taken and used as the 10-hour UACR sample. Least Square Means and Standard error were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based 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 Least Squares Mean (Standard error) at Week 20 is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (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 Urine Albumin Creatinine Ratio (UACR) measured in First Morning Void urine 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. Least Square Means and Standard error were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based 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 Least Squares Mean (Standard error) at Week 20 is reported. |
| Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | Baseline (day -14 and -7) and week 20 (day 141). | 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 is reported. As soon as the First Morning Void sample was collected the clock starts for the 10-hour urine collection. During the 10-hour period every time the patient urinates, they 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 | Baseline (day -14 and -7) and week 20 (day 141). | Number of patients achieving 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, Hong Kong, Japan, Malaysia, Mexico, Netherlands, New Zealand, Poland, Portugal, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study was a phase II, randomized, double-blind (within dose groups), placebo controlled and parallel group trial in patients with diabetic kidney disease (DKD) to demonstrate the effectiveness of BI 685509 and to characterize the dose-response relationship for BI 685509 in patients with DKD by assessing 3 doses and placebo.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| BI 685509 1 mg TID The patients were administered 1 milligram (mg) BI 685509 Film-coated tablets 3 times a day during 20 weeks of treatment in total, with water and taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first. | 61 |
| BI 685509 2mg TID The patients were administered 1 milligram (mg) BI 685509 Film-coated tablets 3 times a day during the first 2 weeks of treatment, If the medication was tolerated, up-titration to 2 mg TID BI 685509 occurred after 2 weeks until Week 20 of treatment. The tablets were taken with water, with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first. | 61 |
| BI 685509 3 mg TID The patients were administered 1 milligram (mg) BI 685509 Film-coated tablets 3 times a day during the first 2 weeks of treatment, If the medication was tolerated, up-titration to 2 mg TID BI 685509 occurred after 2 weeks until Week 4 of treatment. Then if medication was tolerated, up-titration to 3 mg TID BI 685509 occurred from Week 5 until Week 20.
The tablets were taken with water, with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first. | 61 |
| Placebo This arm comprises all placebo treated participants. Participants were randomized in the dose group in a 3:1 ratio (test treatment to placebo). Participants were administered Film-coated tablets of matching placebo 3 times a day during 20 weeks of treatment. The tablets were taken with water, with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first. | 60 |
| Total | 243 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 10 | 8 | 1 |
| Overall Study | Burden of study procedures | 0 | 2 | 2 | 0 |
| Overall Study | Change of residence | 0 | 0 | 1 | 0 |
| Overall Study | Not treated | 0 | 0 | 0 | 2 |
| Overall Study | Other than listed | 3 | 2 | 2 | 1 |
| Overall Study | Prematurely discontinued | 0 | 0 | 0 | 2 |
| Overall Study | Protocol deviation | 1 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | BI 685509 1 mg TID | BI 685509 2mg TID | BI 685509 3 mg TID | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 65.2 Years STANDARD_DEVIATION 9.3 | 64.8 Years STANDARD_DEVIATION 11 | 65.2 Years STANDARD_DEVIATION 8.8 | 67.6 Years STANDARD_DEVIATION 8.7 | 65.7 Years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 21 Participants | 23 Participants | 21 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 40 Participants | 38 Participants | 39 Participants | 162 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 | 1 Participants | 3 Participants | 3 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) Asian | 23 Participants | 16 Participants | 16 Participants | 16 Participants | 71 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 11 Participants | 10 Participants | 6 Participants | 33 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 31 Participants | 32 Participants | 34 Participants | 127 Participants |
| Sex: Female, Male Female | 16 Participants | 14 Participants | 13 Participants | 16 Participants | 59 Participants |
| Sex: Female, Male Male | 45 Participants | 47 Participants | 48 Participants | 44 Participants | 184 Participants |
| Urine Albumin Creatinine Ratio (UACR) - 10 Hour | 1093.5 milligram/gram (mg/g) STANDARD_DEVIATION 980.3 | 1090.7 milligram/gram (mg/g) STANDARD_DEVIATION 794.4 | 880.8 milligram/gram (mg/g) STANDARD_DEVIATION 722.4 | 913.1 milligram/gram (mg/g) STANDARD_DEVIATION 657.3 | 994.9 milligram/gram (mg/g) STANDARD_DEVIATION 799.5 |
| Urine Albumin Creatinine Ratio (UACR) FMV | 991.7 Milligram/gram (mg/g) STANDARD_DEVIATION 889 | 1033 Milligram/gram (mg/g) STANDARD_DEVIATION 760.4 | 818.4 Milligram/gram (mg/g) STANDARD_DEVIATION 686.9 | 866.1 Milligram/gram (mg/g) STANDARD_DEVIATION 658.1 | 927.5 Milligram/gram (mg/g) STANDARD_DEVIATION 754.8 |
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 / 61 | 1 / 61 | 2 / 61 | 0 / 58 |
| other Total, other adverse events | 13 / 61 | 15 / 61 | 15 / 61 | 14 / 58 |
| serious Total, serious adverse events | 4 / 61 | 8 / 61 | 7 / 61 | 4 / 58 |
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) after 20 weeks is reported. As soon as the First Morning Void sample was collected the clock starts for the 10-hour urine collection. During the 10-hour period every time the patient urinates, they collected their urine into a provided container. An aliquot of this urine was taken and used as the 10-hour UACR sample. Least Square Means and Standard error were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based 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 Least Squares Mean (Standard error) at Week 20 is reported.
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): The patient set included all patients who had at least one baseline measurement of UACR in week -2, -1, or 0 and at least one post-baseline measurement after week 6.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 685509 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 | -0.069 milligram/gram (mg/g) | Standard Error 0.074 |
| BI 685509 2mg TID | Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment | -0.029 milligram/gram (mg/g) | Standard Error 0.079 |
| BI 685509 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 milligram/gram (mg/g) | Standard Error 0.076 |
| Placebo | Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment | 0.034 milligram/gram (mg/g) | Standard Error 0.073 |
Comparison: A flat vs. non-flat dose-response relationship across the 3 doses of BI 685509 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, exponential, quadratic, Emax and 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 BI 685509 3 mg, 6 mg, and 9 mg).p-value: 0.0245MCP-Mod exponential model fit
Comparison: A flat vs. non-flat dose-response relationship across the 3 doses of BI 685509 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, exponential, quadratic, Emax and 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 BI 685509 3 mg, 6 mg, and 9 mg).p-value: 0.0294MCP-Mod linear model fit
p-value: 0.0468MCP-Mod quadratic model fit
Comparison: A flat vs. non-flat dose-response relationship across the 3 doses of BI 685509 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, exponential, quadratic, Emax and 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 BI 685509 3 mg, 6 mg, and 9 mg).p-value: 0.0586MCP-Mod Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 3 doses of BI 685509 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, exponential, quadratic, Emax and 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 BI 685509 3 mg, 6 mg, and 9 mg).p-value: 0.0659MCP-Mod Sigmoid emax model fit
Comparison: Least Square Means difference and 95% confidence interval were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based 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: 0.322495% CI: [-0.309, 0.102]Mixed-effect Model Repeat Measurement
Comparison: Least Square Means difference and 95% confidence interval were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based 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: 0.561695% CI: [-0.275, 0.15]Mixed-effect Model Repeat Measurement
Comparison: Least Square Means difference and 95% confidence interval were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based 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: 0.018395% CI: [-0.459, -0.043]Mixed-effect Model Repeat Measurement
Secondary
Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in First Morning Void Urine After 20 Weeks of Trial Treatment
Change from baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in First Morning Void urine 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. Least Square Means and Standard error were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based 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 Least Squares Mean (Standard error) at Week 20 is reported.
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): The patient set included all patients who had at least one baseline measurement of UACR in week -2, -1, or 0 and at least one post-baseline measurement after week 6.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 685509 1 mg TID | Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in First Morning Void Urine After 20 Weeks of Trial Treatment | -0.112 milligram/gram (mg/g) | Standard Error 0.072 |
| BI 685509 2mg TID | Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in First Morning Void Urine After 20 Weeks of Trial Treatment | -0.020 milligram/gram (mg/g) | Standard Error 0.076 |
| BI 685509 3 mg TID | Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in First Morning Void Urine After 20 Weeks of Trial Treatment | -0.258 milligram/gram (mg/g) | Standard Error 0.074 |
| Placebo | Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in First Morning Void Urine After 20 Weeks of Trial Treatment | 0.099 milligram/gram (mg/g) | Standard Error 0.072 |
Comparison: Least Square Means difference and 95% confidence interval were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based 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: 0.03960.95% CI: [-0.413, -0.01]Mixed Models Analysis
Comparison: Least Square Means difference and 95% confidence interval were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based 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: 0.25680.95% CI: [-0.327, 0.088]Mixed Models Analysis
Comparison: Least Square Means difference and 95% confidence interval were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based 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: 0.00060.95% CI: [-0.56, -0.154]Mixed Models Analysis
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 is reported. As soon as the First Morning Void sample was collected the clock starts for the 10-hour urine collection. During the 10-hour period every time the patient urinates, they collected their urine into a provided container. An aliquot of this urine was taken and used as the 10-hour UACR sample.
Time frame: Baseline (day -14 and -7) and week 20 (day 141).
Population: Full Analysis Set (FAS): The patient set included all patients who had at least one baseline measurement of UACR in week -2, -1, or 0 and at least one post-baseline measurement after week 6.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 685509 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 | 23 Participants |
| BI 685509 2mg TID | Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | 16 Participants |
| BI 685509 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 | 26 Participants |
| Placebo | Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | 13 Participants |
Comparison: Treatment, sodium-Glucose co-Transporter-2 Inhibitor (SGLT2i) use at baseline, and type of diabetes were used as covariates in the logistic regression model.p-value: 0.051995% CI: [0.99, 5.1]Regression, Logistic
Comparison: Treatment, sodium-Glucose co-Transporter-2 Inhibitor (SGLT2i) use at baseline, and type of diabetes were used as covariates in the logistic regression model.p-value: 0.415995% CI: [0.61, 3.36]Regression, Logistic
Comparison: Treatment, sodium-Glucose co-Transporter-2 Inhibitor (SGLT2i) use at baseline, and type of diabetes were used as covariates in the logistic regression model.p-value: 0.010695% CI: [1.28, 6.55]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 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: Baseline (day -14 and -7) and week 20 (day 141).
Population: Full Analysis Set (FAS): The patient set included all patients who had at least one baseline measurement of UACR in week -2, -1, or 0 and at least one post-baseline measurement after week 6.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 685509 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 | 23 Participants |
| BI 685509 2mg TID | Number of Patients Achieving UACR Decreases in First Morning Void Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment | 13 Participants |
| BI 685509 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 | 29 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 | 11 Participants |
Comparison: Treatment, sodium-Glucose co-Transporter-2 Inhibitor (SGLT2i) use at baseline, and type of diabetes were used as covariates in the logistic regression model.p-value: 0.017695% CI: [1.2, 6.53]Regression, Logistic
Comparison: Treatment, sodium-Glucose co-Transporter-2 Inhibitor (SGLT2i) use at baseline, and type of diabetes were used as covariates in the logistic regression model.p-value: 0.546795% CI: [0.53, 3.29]Regression, Logistic
Comparison: Treatment, sodium-Glucose co-Transporter-2 Inhibitor (SGLT2i) use at baseline, and type of diabetes were used as covariates in the logistic regression model.p-value: 0.000595% CI: [1.91, 10.39]Regression, Logistic