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Clinical Trial Results:
Randomised, double-blind, placebo-controlled and parallel dose group trial to investigate efficacy and safety of multiple doses of oral BI 690517 over 14 weeks, alone and in combination with empagliflozin, in patients with diabetic and non-diabetic chronic kidney disease

Summary
EudraCT number	2021-001434-19
Trial protocol	BE FI IT NO SE CZ HU ES DK BG GR PT PL
Global end of trial date	10 Jul 2023

Results information
Results version number	v2(current)
This version publication date	04 Oct 2024
First version publication date	21 Jul 2024
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

1378.5

ISRCTN number

US NCT number

NCT05182840

WHO universal trial number (UTN)

Sponsor organisation name

Boehringer Ingelheim

Sponsor organisation address

Binger Strasse 173, Ingelheim am Rhein, Germany, 55216

Public contact

Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com

Scientific contact

Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

01 Aug 2023

Is this the analysis of the primary completion data?

Yes

Primary completion date

19 Jun 2023

Global end of trial reached?

Yes

Global end of trial date

10 Jul 2023

Was the trial ended prematurely?

Main objective of the trial

The main objectives of the trial were to demonstrate the efficacy of BI 690517, alone and in combination with empagliflozin, and to characterise the BI 690517 dose-response relationship in patients with diabetic and non-diabetic chronic kidney disease (CKD) by assessing three doses and placebo.

Protection of trial subjects

Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all subjects as required.

Background therapy

Evidence for comparator

Actual start date of recruitment

02 Feb 2022

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 128

Country: Number of subjects enrolled

Australia: 10

Country: Number of subjects enrolled

Belgium: 24

Country: Number of subjects enrolled

Brazil: 204

Country: Number of subjects enrolled

Bulgaria: 36

Country: Number of subjects enrolled

Canada: 20

Country: Number of subjects enrolled

China: 21

Country: Number of subjects enrolled

Czechia: 16

Country: Number of subjects enrolled

Finland: 30

Country: Number of subjects enrolled

Germany: 43

Country: Number of subjects enrolled

Greece: 15

Country: Number of subjects enrolled

Hong Kong: 6

Country: Number of subjects enrolled

Hungary: 41

Country: Number of subjects enrolled

India: 63

Country: Number of subjects enrolled

Italy: 9

Country: Number of subjects enrolled

Japan: 84

Country: Number of subjects enrolled

Korea, Republic of: 21

Country: Number of subjects enrolled

Malaysia: 31

Country: Number of subjects enrolled

Mexico: 70

Country: Number of subjects enrolled

Norway: 7

Country: Number of subjects enrolled

Philippines: 127

Country: Number of subjects enrolled

Poland: 75

Country: Number of subjects enrolled

Portugal: 22

Country: Number of subjects enrolled

South Africa: 58

Country: Number of subjects enrolled

Spain: 24

Country: Number of subjects enrolled

Sweden: 4

Country: Number of subjects enrolled

Switzerland: 2

Country: Number of subjects enrolled

Türkiye: 5

Country: Number of subjects enrolled

United States: 518

Worldwide total number of subjects

1714

EEA total number of subjects

346

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

764

From 65 to 84 years

950

85 years and over

Subject disposition

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Recruitment details

In the run-in period patients got empagliflozin or placebo to empagliflozin. The run-in period was followed by a second randomization at which patients were 1:1:1:1 randomized to a treatment period to receive one of three doses of BI 690517 or placebo matching BI 690517 in combination with the background medication assigned in the run-in period.

Screening details

Due to limitations of the EudraCT Results Form 2 patients who did not complete the Run-in period (RP) for the Placebo arm are entered under the milestone completed of the RP. The 2 patients who did not complete the RP were mistakenly randomized to the treatment period (TP) but were not treated during the TP with BI 690517 or placebo to BI 690517.

Period 1 title

Run-in period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Data analyst, Assessor

Blinding implementation details

Patients, investigators and everyone involved in trial conduct or analysis or with any other interest in this double-blind trial remained blinded with regard to the randomised treatment assignments.

Are arms mutually exclusive

Yes

Run-in period: 10 mg Empa

Arm description

Patients received during the run-in period 10 milligrams (mg) of empagliflozin (Empa) once daily orally for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Empagliflozin film-coated tablets 10mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received during the run-in period one film-coated tablet of 10 milligrams (mg) of empagliflozin (Empa) once daily orally for 8 weeks.

Run-in period: Placebo to Empa 10 mg

Arm description

Patients received during the run-in period placebo matching empagliflozin (Empa) 10 milligrams (mg) once daily orally for 8 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to empagliflozin film-coated tablets 10mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received during the run-in period one film-coated tablet of 10 milligrams (mg) of placebo matching empagliflozin (Empa) once daily orally for 8 weeks.

Number of subjects in period 1	Run-in period: 10 mg Empa	Run-in period: Placebo to Empa 10 mg
Started	356	358
Treated with Empa or Placebo to Empa	356	357
Completed	332	332
Not completed	24	26
Adverse event, non-fatal	5	5
No reason available	2	2
Burden of study procedures	2	2
Other reason but not sponsor termination	14	16
Change of residence	1	-
Not treated	-	1

Period 2 title

Screened for treatment period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Data analyst, Assessor

Blinding implementation details

Patients, investigators and everyone involved in trial conduct or analysis or with any other interest in this double-blind trial remained blinded with regard to the randomised treatment assignments.

Are arms mutually exclusive

Yes

Run-in period: 10 mg Empa

Arm description

Patients received during the run-in period 10 milligrams (mg) of empagliflozin (Empa) once daily orally for 8 weeks.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Run-in period: Placebo to Empa 10 mg

Arm description

Patients received during the run-in period placebo matching empagliflozin (Empa) 10 milligrams (mg) once daily orally for 8 weeks.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	Run-in period: 10 mg Empa	Run-in period: Placebo to Empa 10 mg
Started	332	332
Completed the RP and screened for TP	332	330
Entered to TP without completing the RP	0 ^[1]	2 ^[2]
Completed	298	288
Not completed	34	44
Did not meet Treatment Period eligibility criteria	34	44

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only 2 patients in the arm were eligible for this milestone.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: None of the patients who in this arm were eligible for this milestone.

Period 3 title

Treatment period

Is this the baseline period?

Yes ^[3]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Data analyst, Assessor

Blinding implementation details

Patients, investigators and everyone involved in trial conduct or analysis or with any other interest in this double-blind trial remained blinded with regard to the randomised treatment assignments.

Are arms mutually exclusive

Yes

Treatment period: 10 mg Empa + 3 mg BI 690517

Arm description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 3 milligrams (mg) of BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received 3 mg BI 690517 and 10 mg empagliflozin for 14 weeks.

Arm type

Experimental

Investigational medicinal product name

Empagliflozin film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 10 mg of empagliflozin once daily (QD) orally for 14 weeks.

Investigational medicinal product name

BI 690517 film-coated tablets 3 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 3 milligrams (mg) of BI 690517 once daily (QD) for 14 weeks.

Treatment period: 10 mg Empa + 10 mg BI 690517

Arm description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 10 milligrams (mg) of BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received 10 mg BI 690517 and 10 mg empagliflozin for 14 weeks.

Arm type

Experimental

Investigational medicinal product name

Empagliflozin film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 10 mg of empagliflozin once daily (QD) orally for 14 weeks.

Investigational medicinal product name

BI 690517 film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 10 milligrams (mg) of BI 690517 orally for 14 weeks.

Treatment period: 10 mg Empa + 20 mg BI 690517

Arm description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 20 milligrams (mg) of BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received 20 mg BI 690517 and 10 mg empagliflozin for 14 weeks.

Arm type

Experimental

Investigational medicinal product name

Empagliflozin film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 10 mg of empagliflozin once daily (QD) orally for 14 weeks.

Investigational medicinal product name

BI 690517 film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received two film-coated tablets of 10 milligrams (mg) of BI 690517 (total BI 690517 dose=20 mg) orally for 14 weeks.

Treatment period: 10 mg Empa + Placebo to BI 690517

Arm description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received placebo matching BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received placebo matching BI 690517 and 10 mg empagliflozin for 14 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to BI 690517 film-coated tablets 3 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 3 mg of placebo to BI 690517 orally for 14 weeks.

Investigational medicinal product name

Empagliflozin film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 10 mg of empagliflozin once daily (QD) orally for 14 weeks.

Investigational medicinal product name

Placebo to BI 690517 film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received either one film-coated tablet of 10 mg of placebo to BI 690517 or 2 film-coated tablets of 10 mg of placebo to BI 690517 orally for 14 weeks.

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517

Arm description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 3 mg of BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received 3 mg BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Arm type

Experimental

Investigational medicinal product name

Placebo to empagliflozin film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 10 milligrams (mg) of placebo to empagliflozin once daily (QD) orally for 14 weeks.

Investigational medicinal product name

BI 690517 film-coated tablets 3 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 3 milligrams (mg) of BI 690517 once daily (QD) orally for 14 weeks.

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517

Arm description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 10 mg of BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received 10 mg BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Arm type

Experimental

Investigational medicinal product name

Placebo to empagliflozin film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 10 milligrams (mg) of placebo to empagliflozin once daily (QD) orally for 14 weeks.

Investigational medicinal product name

BI 690517 film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 10 milligrams (mg) of BI 690517 once daily (QD) orally for 14 weeks.

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517

Arm description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 20 mg of BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received 20 mg BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Arm type

Experimental

Investigational medicinal product name

Placebo to empagliflozin film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 10 milligrams (mg) of placebo to empagliflozin once daily (QD) orally for 14 weeks.

Investigational medicinal product name

BI 690517 film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received two film-coated tablets of 10 milligrams (mg) of BI 690517 (total BI 690517 dose=20 mg) orally for 14 weeks.

Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Arm description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received placebo matching BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received placebo matching BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to BI 690517 film-coated tablets 3 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 3 mg of placebo to BI 690517 orally for 14 weeks.

Investigational medicinal product name

Placebo to BI 690517 film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received either one film-coated tablet of 10 mg of placebo to BI 690517 or 2 film-coated tablets of 10 mg of placebo to BI 690517 orally for 14 weeks.

Investigational medicinal product name

Empagliflozin film-coated tablets 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients received one film-coated tablet of 10 milligrams (mg) of placebo to empagliflozin once daily (QD) orally for 14 weeks.

Notes
[3] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: Baseline characteristics are reported for the participants who started the Treatment Period. 586 subjects were randomized to treatment period.

Number of subjects in period 3 ^[4]	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517
Started	76	74	74	74	71	72	72	73
Got BI 690517/Placebo to BI 690517	76	73	74	74	70	71	72	73
Completed	63	50	55	58	61	54	48	66
Not completed	13	24	19	16	10	18	24	7
Adverse event, non-fatal	4	16	12	6	4	8	16	5
Did not get BI/Placebo to BI	-	1	-	-	1	1	-	-
No reason available	-	1	-	2	-	1	-	-
Protocol deviation	-	-	-	-	-	-	1	-
Burden of study procedures	-	-	1	-	-	-	-	-
Change of residence	-	-	-	1	-	-	-	-
Other but not sponsor termination	8	6	6	7	5	8	7	2
Reason missing	1	-	-	-	-	-	-	-

Notes
[4] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Out of 1714 participants that were screened only 714 were randomized to the Run-in period.

Baseline characteristics

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Reporting group title

Treatment period: 10 mg Empa + 3 mg BI 690517

Reporting group description

Reporting group title

Treatment period: 10 mg Empa + 10 mg BI 690517

Reporting group description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 10 milligrams (mg) of BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received 10 mg BI 690517 and 10 mg empagliflozin for 14 weeks.

Reporting group title

Treatment period: 10 mg Empa + 20 mg BI 690517

Reporting group description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 20 milligrams (mg) of BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received 20 mg BI 690517 and 10 mg empagliflozin for 14 weeks.

Reporting group title

Treatment period: 10 mg Empa + Placebo to BI 690517

Reporting group description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received placebo matching BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received placebo matching BI 690517 and 10 mg empagliflozin for 14 weeks.

Reporting group title

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517

Reporting group description

Reporting group title

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517

Reporting group description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 10 mg of BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received 10 mg BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Reporting group title

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517

Reporting group description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 20 mg of BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received 20 mg BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Reporting group title

Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Reporting group description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received placebo matching BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received placebo matching BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Reporting group values	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517	Total
Number of subjects	76	74	74	74	71	72	72	73	586
Age categorical
Randomised Set (RS): included all entered and randomised patients based on the treatment groups they were randomised to at the randomisation prior to the treatment period (i.e. at second randomisation (R2)), regardless of being treated by BI 690517 or not.
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	32	30	40	35	32	30	29	39	267
From 65-84 years	41	44	33	39	37	41	42	34	311
85 years and over	3	0	1	0	2	1	1	0	8
Age Continuous
Randomised Set (RS): included all entered and randomised patients based on the treatment groups they were randomised to at the randomisation prior to the treatment period (i.e. at second randomisation (R2)), regardless of being treated by BI 690517 or not.
Units: years
arithmetic mean (standard deviation)	65.4 ( 11.2 )	64.4 ( 12.3 )	61.8 ( 12.2 )	63.4 ( 10.3 )	64.4 ( 11.8 )	64.8 ( 9.9 )	64.3 ( 10.7 )	62.3 ( 11.4 )	-
Sex: Female, Male
Randomised Set (RS): included all entered and randomised patients based on the treatment groups they were randomised to at the randomisation prior to the treatment period (i.e. at second randomisation (R2)), regardless of being treated by BI 690517 or not.
Units: Participants
Male	49	44	54	43	51	49	45	55	390
Female	27	30	20	31	20	23	27	18	196
Ethnicity (NIH/OMB)
Randomised Set (RS): included all entered and randomised patients based on the treatment groups they were randomised to at the randomisation prior to the treatment period (i.e. at second randomisation (R2)), regardless of being treated by BI 690517 or not.
Units: Subjects
Hispanic or Latino	25	21	12	20	22	21	18	24	163
Not Hispanic or Latino	51	53	62	54	49	51	54	49	423
Unknown or Not Reported	0	0	0	0	0	0	0	0	0
Race (NIH/OMB)
Randomised Set (RS): included all entered and randomised patients based on the treatment groups they were randomised to at the randomisation prior to the treatment period (i.e. at second randomisation (R2)), regardless of being treated by BI 690517 or not.
Units: Subjects
American Indian or Alaska Native	0	2	1	2	2	2	3	1	13
Asian	17	27	20	19	23	15	19	16	156
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	1	1
Black or African American	9	6	7	10	3	9	9	10	63
White	49	35	45	42	42	45	40	44	342
More than one race	1	4	1	1	1	1	1	1	11
Unknown or Not Reported	0	0	0	0	0	0	0	0	0
Urine Albumin Creatinine Ratio (UACR) at baseline
UACR is a ratio between two measured substances i.e., albumine and creatinine and it is calculated as: (Urine albumin (milligram (mg)/deciliter (dL)))/(urine creatinine gram (g)/deciliter (dL))= UACR in mg/g. Albuminuria is present when UACR is greater than 30 mg/g and is a marker for chronic kidney disease (CKD). UACR measurements were collected on 2 consecutive days at 3 timepoints from Week -2 to Week 0 (i.e. Week 6-8 of Run-in period) for treatment period baseline. The randomised set (RS) was used to report the UACR at baseline.
Units: milligram/gram
arithmetic mean (standard deviation)	780.3 ( 828.8 )	740.8 ( 915.0 )	695.4 ( 748.0 )	801.4 ( 1132.3 )	934.0 ( 1363.6 )	646.2 ( 685.2 )	785.0 ( 885.7 )	684.4 ( 715.1 )	-

End points

Top of page

Reporting group title

Run-in period: 10 mg Empa

Reporting group description

Patients received during the run-in period 10 milligrams (mg) of empagliflozin (Empa) once daily orally for 8 weeks.

Reporting group title

Run-in period: Placebo to Empa 10 mg

Reporting group description

Patients received during the run-in period placebo matching empagliflozin (Empa) 10 milligrams (mg) once daily orally for 8 weeks.

Reporting group title

Run-in period: 10 mg Empa

Reporting group description

Patients received during the run-in period 10 milligrams (mg) of empagliflozin (Empa) once daily orally for 8 weeks.

Reporting group title

Run-in period: Placebo to Empa 10 mg

Reporting group description

Patients received during the run-in period placebo matching empagliflozin (Empa) 10 milligrams (mg) once daily orally for 8 weeks.

Reporting group title

Treatment period: 10 mg Empa + 3 mg BI 690517

Reporting group description

Reporting group title

Treatment period: 10 mg Empa + 10 mg BI 690517

Reporting group description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 10 milligrams (mg) of BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received 10 mg BI 690517 and 10 mg empagliflozin for 14 weeks.

Reporting group title

Treatment period: 10 mg Empa + 20 mg BI 690517

Reporting group description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 20 milligrams (mg) of BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received 20 mg BI 690517 and 10 mg empagliflozin for 14 weeks.

Reporting group title

Treatment period: 10 mg Empa + Placebo to BI 690517

Reporting group description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received placebo matching BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received placebo matching BI 690517 and 10 mg empagliflozin for 14 weeks.

Reporting group title

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517

Reporting group description

Reporting group title

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517

Reporting group description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 10 mg of BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received 10 mg BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Reporting group title

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517

Reporting group description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 20 mg of BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received 20 mg BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Reporting group title

Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Reporting group description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received placebo matching BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received placebo matching BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Subject analysis set title

3 mg BI 690517

Subject analysis set type

Full analysis

Subject analysis set description

This arm includes patients who received during the Treatment Period 3 milligram (mg) of BI 690517 + 10 mg Empagliflozin (i.e. arm "Treatment period: 10 mg empagliflozin + 3 mg BI 690517" in the Participant Flow) and patients who received during the Treatment period 3 mg BI 690517 + Placebo matching Empagliflozin 10 mg (i.e. arm "Treatment period: Placebo to empagliflozin 10 mg + 3 mg BI 690517" in the Participant Flow).

Subject analysis set title

10 mg BI 690517

Subject analysis set type

Full analysis

Subject analysis set description

This arm includes patients who received during the Treatment Period 10 milligram (mg) of BI 690517 + 10 mg Empagliflozin (i.e. arm "Treatment period: 10 mg empagliflozin + 10 mg BI 690517" in the Participant Flow) and patients who received during the Treatment period 10 mg BI 690517 + Placebo matching Empagliflozin 10 mg (i.e. arm "Treatment period: Placebo to empagliflozin 10 mg + 10 mg BI 690517" in the Participant Flow).

Subject analysis set title

20 mg BI 690517

Subject analysis set type

Full analysis

Subject analysis set description

This arm includes patients who received during the Treatment Period 20 milligram (mg) of BI 690517 + 10 mg Empagliflozin (i.e. arm "Treatment period: 10 mg empagliflozin + 20 mg BI 690517" in the Participant Flow) and patients who received during the Treatment period 20 mg BI 690517 + Placebo matching Empagliflozin 10 mg (i.e. arm "Treatment period: Placebo to empagliflozin 10 mg + 20 mg BI 690517" in the Participant Flow).

Subject analysis set title

Placebo to BI 690517

Subject analysis set type

Full analysis

Subject analysis set description

This arm includes patients who received during the Treatment Period Placebo to BI 690517 + 10 mg Empagliflozin (i.e. arm "Treatment period: 10 mg empagliflozin + Placebo to BI 690517" in the Participant Flow) and patients who received during the Treatment period Placebo to BI 690517 + Placebo matching Empagliflozin 10 mg (i.e. arm "Treatment period: Placebo to empagliflozin 10 mg + Placebo to BI 690517" in the Participant Flow).

Subject analysis set title

3 mg BI 690517

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

BI 690517 3 mg

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

3 mg BI 690517

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

10 mg BI 690517

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

20 mg BI 690517

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Placebo to BI 690517

Subject analysis set type

Full analysis

Subject analysis set description

Primary: Change from treatment period baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in First Morning Void (FMV) urine after 14 weeks - all patients

Top of page

End point title

Change from treatment period baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in First Morning Void (FMV) urine after 14 weeks - all patients

End point description

The adjusted mean change (95% confidence interval) in log transformed FMV UACR from baseline at 14 weeks is presented. The adjusted means and 95 % confidence intervals were estimated by restricted maximum likelihood-based mixed models for repeated measures ((REML)−based MMRM) which includes the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient. Full Analysis Set (FAS): This patient set included all randomised patients to one of 3 doses of BI 690517 (3mg QD, 10 mg QD or 20 mg QD) or placebo matching BI 690517 who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6, 7 or 8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment of BI 690517 or placebo matching BI 690517.

End point type

Primary

End point timeframe

The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period.

End point values	3 mg BI 690517	10 mg BI 690517	20 mg BI 690517	Placebo to BI 690517
Number of subjects analysed	128	121	121	133
Units: log transformed FMV UACR
least squares mean (confidence interval 95%)	-0.235 (-0.355 to -0.114)	-0.553 (-0.681 to -0.425)	-0.487 (-0.616 to -0.357)	-0.066 (-0.184 to 0.051)

Statistical analysis 1

Statistical analysis description

The difference of adjusted means and 95 % confidence interval were estimated by restricted maximum likelihood-based mixed models for repeated measures ((REML)−based MMRM) which included the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient.

Comparison groups

3 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

261

Analysis specification

Pre-specified

Analysis type

other ^[1]

P-value

= 0.0499

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.168

Confidence interval

level

95%

sides

2-sided

lower limit

-0.337

upper limit

Notes
[1] - Least Squares Mean of "3 mg BI 690517" - Least Squares Mean of "Placebo to BI 690517".

Statistical analysis 2

Statistical analysis description

Comparison groups

10 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[2]

P-value

< 0.0001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.486

Confidence interval

level

95%

sides

2-sided

lower limit

-0.66

upper limit

-0.313

Notes
[2] - Least Squares Mean of "10 mg BI 690517" - Least Squares Mean of "Placebo to BI 690517".

Statistical analysis 5

Statistical analysis description

A flat vs. non-flat dose-response relationship across the 3 doses of BI 690517 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod). MMRM estimates were used as input for the MCP-Mod. MMRM included the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient.

Comparison groups

3 mg BI 690517 v 10 mg BI 690517 v 20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

503

Analysis specification

Pre-specified

Analysis type

other ^[3]

P-value

= 0 ^[4]

Method

MCPMod linear model fit

Confidence interval

Notes
[3] - Null hypothesis: The dose-response curve is flat across the 3 BI 690517 doses and the placebo. Linear model fit assumption: No assumption is needed.
[4] - P-value was rounded to four decimal places.

Statistical analysis 4

Statistical analysis description

Comparison groups

3 mg BI 690517 v 10 mg BI 690517 v 20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

503

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

= 0 ^[6]

Method

MCPMod Emax model fit

Confidence interval

Notes
[5] - Null hypothesis: The dose-response curve is flat across the 3 BI 690517 doses and the placebo. Emax model fit assumption: 80% of the maximum effect is achieved at 10 mg.
[6] - P-value was rounded to four decimal places.

Statistical analysis 6

Statistical analysis description

Comparison groups

3 mg BI 690517 v 10 mg BI 690517 v 20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

503

Analysis specification

Pre-specified

Analysis type

other ^[7]

P-value

= 0.0003

Method

MCPMod exponential model fit

Confidence interval

Notes
[7] - Null hypothesis: The dose-response curve is flat across the 3 BI 690517 doses and the placebo. Exponential model fit assumption: 15% of the maximum effect is achieved at 10 mg.

Statistical analysis 3

Statistical analysis description

Comparison groups

20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[8]

P-value

< 0.0001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.421

Confidence interval

level

95%

sides

2-sided

lower limit

-0.596

upper limit

-0.246

Notes
[8] - Least Squares Mean of "20 mg BI 690517" - Least Squares Mean of "Placebo to BI 690517".

Primary: Percent change of FMV UACR from baseline to Week 14 based on adjusted median (95% CI) back transformed from MMRM estimate - all patients

Top of page

End point title

Percent change of FMV UACR from baseline to Week 14 based on adjusted median (95% CI) back transformed from MMRM estimate - all patients

End point description

Percent change of first morning void (FMV) urine albumine creatinine ratio (UACR) from baseline to Week 14 based on adjusted median (95% confidence interval (CI)) back transformed from mixed models for repeated measures (MMRM) estimate for all patients is presented. Percent change of FMV UACR= (FMV UACR at Week 14-FMV UACR at baseline)*100/(FMV UACR at baseline). MMRM included the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient. Full analysis set was used for the analysis of this endpoint.

End point type

Primary

End point timeframe

The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period.

End point values	3 mg BI 690517	10 mg BI 690517	20 mg BI 690517	Placebo to BI 690517
Number of subjects analysed	128	121	121	133
Units: percent change of FMV UACR
median (confidence interval 95%)	-20.9 (-29.9 to -10.8)	-42.5 (-49.4 to -34.6)	-38.5 (-46.0 to -30.0)	-6.4 (-16.8 to 5.3)

Statistical analysis 1

Comparison groups

3 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

261

Analysis specification

Pre-specified

Analysis type

other ^[9]

Method

Parameter type

Median difference (net)

Point estimate

-15.5

Confidence interval

level

95%

sides

2-sided

lower limit

-28.6

upper limit

Notes
[9] - Median of "3 mg BI 690517" - Median of "Placebo to BI 690517"

Statistical analysis 3

Comparison groups

20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[10]

Method

Parameter type

Median difference (net)

Point estimate

-34.3

Confidence interval

level

95%

sides

2-sided

lower limit

-44.9

upper limit

-21.8

Notes
[10] - Median of "10 mg BI 690517" - Median of "Placebo to BI 690517".

Statistical analysis 2

Comparison groups

10 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[11]

Method

Parameter type

Median difference (net)

Point estimate

-38.5

Confidence interval

level

95%

sides

2-sided

lower limit

-48.3

upper limit

-26.8

Notes
[11] - Median of "10 mg BI 690517" - Median of "Placebo to BI 690517".

Primary: Change from baseline to Week 14 in the log transformed FMV UACR − patients with background therapy of placebo matching empagliflozin

Top of page

End point title

Change from baseline to Week 14 in the log transformed FMV UACR − patients with background therapy of placebo matching empagliflozin ^[12]

End point description

The adjusted mean change (95% confidence interval) in log transformed first morning void (FMV) urine albumine creatinine ratio (UACR) from baseline at 14 weeks for patients with background therapy of placebo matching empagliflozin in the Run-in period is presented. The adjusted means and 95 % confidence intervals were estimated by restricted maximum likelihood-based mixed models for repeated measures ((REML)−based MMRM) which includes the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient. This endpoint is reported for the patients in the full analysis set who received placebo to empagliflozin during the Run-in period and had UACR measurement at baseline and at least one post-baseline UACR measurement while still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Primary

End point timeframe

The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period.

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received placebo matching empagliflozin during the Run-in period.

End point values	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517
Number of subjects analysed	65	61	59	69
Units: log transformed FMV UACR
least squares mean (confidence interval 95%)	-0.254 (-0.441 to -0.068)	-0.496 (-0.693 to -0.299)	-0.455 (-0.666 to -0.245)	-0.027 (-0.208 to 0.155)

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

other ^[13]

P-value

= 0.0867

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.227

Confidence interval

level

95%

sides

2-sided

lower limit

-0.488

upper limit

0.033

Notes
[13] - Least Squares Mean of "Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517" - Least Squares Mean of "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[14]

P-value

= 0.0027

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.429

Confidence interval

level

95%

sides

2-sided

lower limit

-0.707

upper limit

-0.151

Notes
[14] - Least Squares Mean of "Treatment period: Placebo to Empa 10 mg + 20 mg BI 6905177" - Least Squares Mean of "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other ^[15]

P-value

= 0.0007

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.469

Confidence interval

level

95%

sides

2-sided

lower limit

-0.737

upper limit

-0.201

Notes
[15] - Least Squares Mean of "Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517" - Least Squares Mean of "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".

Primary: Percent change of FMV UACR from baseline to Week 14 based on adjusted median (95% CI) back transformed from MMRM estimate − patients with background therapy of placebo matching empagliflozin

Top of page

End point title

Percent change of FMV UACR from baseline to Week 14 based on adjusted median (95% CI) back transformed from MMRM estimate − patients with background therapy of placebo matching empagliflozin ^[16]

End point description

Percent change of first morning void (FMV) urine albumine creatinine ratio (UACR) from baseline to Week 14 based on adjusted median (95% confidence interval (CI)) back transformed from mixed models for repeated measures (MMRM) estimate for patients with background therapy of placebo matching empagliflozin in the Run-in period is presented. Percent change of FMV UACR= (FMV UACR at Week 14-FMV UACR at baseline)*100/(FMV UACR at baseline). MMRM included the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient. This endpoint is reported for the patients in the FAS who received placebo to empagliflozin during the Run-in period and had UACR measurement at baseline and at least one post-baseline UACR measurement while still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Primary

End point timeframe

The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period.

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received placebo matching empagliflozin during the Run-in period.

End point values	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517
Number of subjects analysed	65	61	59	69
Units: percent change of FMV UACR
median (confidence interval 95%)	-22.4 (-35.6 to -6.5)	-39.1 (-50.0 to -25.8)	-36.6 (-48.6 to -21.7)	-2.6 (-18.8 to 16.8)

Statistical analysis 1

Comparison groups

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

other ^[17]

Method

Parameter type

Median difference (net)

Point estimate

-20.3

Confidence interval

level

95%

sides

2-sided

lower limit

-38.6

upper limit

3.4

Notes
[17] - Median of "Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517" - median of "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".

Statistical analysis 3

Comparison groups

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[18]

Method

Parameter type

Median difference (net)

Point estimate

-34.9

Confidence interval

level

95%

sides

2-sided

lower limit

-50.7

upper limit

-14

Notes
[18] - Median of "Treatment period: Placebo to Empa 10 mg + 20 mg BI 6905177" - median of "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".

Statistical analysis 2

Statistical analysis description

Median of "Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517" - median of "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517"

Comparison groups

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (net)

Point estimate

-37.4

Confidence interval

level

95%

sides

2-sided

lower limit

-52.2

upper limit

-18.2

Primary: Change from baseline to Week 14 in the log transformed FMV UACR − patients with background therapy of empagliflozin

Top of page

End point title

Change from baseline to Week 14 in the log transformed FMV UACR − patients with background therapy of empagliflozin ^[19]

End point description

The adjusted mean change (95% confidence interval) in log transformed first morning void (FMV) urine albumine creatinine ratio (UACR) from baseline at 14 weeks for patients with background therapy of empagliflozin in the Run-in period is presented. The adjusted means and 95 % confidence intervals were estimated by restricted maximum likelihood-based mixed models for repeated measures ((REML)−based MMRM) which includes the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient. This endpoint is reported for the patients in the FAS who received empagliflozin during the Run-in period and had UACR measurement at baseline and at least one post-baseline UACR measurement while still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Primary

End point timeframe

The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period.

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received empagliflozin during the Run-in period.

End point values	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517
Number of subjects analysed	63	60	62	64
Units: log transformed FMV UACR
least squares mean (confidence interval 95%)	-0.210 (-0.366 to -0.055)	-0.614 (-0.783 to -0.445)	-0.516 (-0.675 to -0.357)	-0.112 (-0.264 to 0.040)

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 3 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

other ^[20]

P-value

= 0.3737

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.098

Confidence interval

level

95%

sides

2-sided

lower limit

-0.316

upper limit

0.119

Notes
[20] - Least Squares Mean of "Treatment period: 10 mg Empa + 3 mg BI 690517" - Least Squares Mean of "Treatment period: 10 mg Empa + Placebo to BI 690517".

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 20 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other ^[21]

P-value

= 0.0004

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.404

Confidence interval

level

95%

sides

2-sided

lower limit

-0.625

upper limit

-0.184

Notes
[21] - Least Squares Mean of "Treatment period: 10 mg Empa + 20 mg BI 690517" - Least Squares Mean of "Treatment period: 10 mg Empa + Placebo to BI 690517".

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 10 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

other ^[22]

P-value

< 0.0001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.502

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

-0.275

Notes
[22] - Least Squares Mean of "Treatment period: 10 mg Empa + 10 mg BI 690517" - Least Squares Mean of "Treatment period: 10 mg Empa + Placebo to BI 690517".

Primary: Percent change of FMV UACR from baseline to Week 14 based on adjusted median (95% CI) of MMRM estimate − patients with background therapy of empagliflozin

Top of page

End point title

Percent change of FMV UACR from baseline to Week 14 based on adjusted median (95% CI) of MMRM estimate − patients with background therapy of empagliflozin ^[23]

End point description

Percent change of first morning void (FMV) urine albumine creatinine ratio (UACR) from baseline to Week 14 based on adjusted median (95% confidence interval (CI)) back transformed from mixed models for repeated measures (MMRM) estimate for patients with background therapy of empagliflozin in the Run-in period is presented. Percent change of FMV UACR= (FMV UACR at Week 14-FMV UACR at baseline)*100/(FMV UACR at baseline). MMRM included the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient. This endpoint is reported for the patients in the FAS who received empagliflozin during the Run-in period and had UACR measurement at baseline and at least one post-baseline UACR measurement while still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Primary

End point timeframe

The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period.

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received empagliflozin during the Run-in period.

End point values	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517
Number of subjects analysed	63	60	62	64
Units: percent change of FMV UACR
median (confidence interval 95%)	-19.0 (-30.6 to -5.4)	-45.9 (-54.3 to -35.9)	-40.3 (-49.1 to -30.0)	-10.6 (-23.2 to 4.1)

Statistical analysis 1

Comparison groups

Treatment period: 10 mg Empa + 3 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

other ^[24]

Method

Parameter type

Median difference (net)

Point estimate

-9.4

Confidence interval

level

95%

sides

2-sided

lower limit

-27.1

upper limit

12.7

Notes
[24] - Median of "Treatment period: 10 mg Empa + 3 mg BI 690517" - median of "Treatment period: 10 mg Empa + Placebo to BI 690517".

Statistical analysis 3

Comparison groups

Treatment period: 10 mg Empa + 20 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other ^[25]

Method

Parameter type

Median difference (net)

Point estimate

-33.2

Confidence interval

level

95%

sides

2-sided

lower limit

-46.5

upper limit

-16.8

Notes
[25] - Median of "Treatment period: 10 mg Empa + 20 mg BI 690517" - median of "Treatment period: 10 mg Empa + Placebo to BI 690517".

Statistical analysis 2

Statistical analysis description

Median of "Treatment period: 10 mg Empa + 10 mg BI 690517" - median of "Treatment period: 10 mg Empa + Placebo to BI 690517".

Comparison groups

Treatment period: 10 mg Empa + 10 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (net)

Point estimate

-39.5

Confidence interval

level

95%

sides

2-sided

lower limit

-51.8

upper limit

-24

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Multiple imputation

Top of page

End point title

UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Multiple imputation

End point description

Number of patients with UACR response I is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. The multiple imputation filled in missing values at Week 14 based on other data observed in the same patient using regression. This endpoint is reporting statistics for the Full Analysis Set (FAS). FAS included all randomised patients who had at least one baseline measurement of UACR at Week -2, -1, or 0 and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the multiple imputation approach.

End point values	3 mg BI 690517	10 mg BI 690517	20 mg BI 690517	Placebo to BI 690517
Number of subjects analysed	128	121	121	133
Units: Participants	40	73	66	24

Statistical analysis 1

Statistical analysis description

The odds ratio, 95% confidence interval, and p-value were calculated based on logistic regression of binary outcome adjusting for treatment, and stratification factors as covariates. Randomisation stratification was used, which is based on estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR) levels at screening.

Comparison groups

3 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

261

Analysis specification

Pre-specified

Analysis type

other ^[26]

P-value

= 0.0136 ^[27]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.08

Confidence interval

level

95%

sides

2-sided

lower limit

1.16

upper limit

3.72

Notes
[26] - Odds ratio of "3 mg BI 690517" vs. "Placebo to BI 690517".
[27] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[28]

P-value

= 0 ^[29]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.48

Confidence interval

level

95%

sides

2-sided

lower limit

3.09

upper limit

9.71

Notes
[28] - Odds ratio of "20 mg BI 690517" vs. "Placebo to BI 690517".
[29] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

10 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[30]

P-value

= 0 ^[31]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.02

Confidence interval

level

95%

sides

2-sided

lower limit

3.94

upper limit

12.49

Notes
[30] - Odds ratio of "10 mg BI 690517" vs. "Placebo to BI 690517".
[31] - P-value was rounded to four decimal places.

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Missing as non−responder

Top of page

End point title

UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Missing as non−responder

End point description

Number of patients with UACR response I is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. The missing as non-responder imputes patients with missing Week 14 data as non-responders. This endpoint is reporting statistics for Full Analysis Set (FAS). FAS included all randomised patients to one of 3 doses of BI 690517 (3mg QD, 10 mg QD or 20 mg QD) or placebo matching BI 690517 who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6, 7 or 8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period.

End point values	3 mg BI 690517	10 mg BI 690517	20 mg BI 690517	Placebo to BI 690517
Number of subjects analysed	128	121	121	133
Units: Participants	40	62	57	23

Statistical analysis 1

Statistical analysis description

Comparison groups

3 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

261

Analysis specification

Pre-specified

Analysis type

other ^[32]

P-value

= 0.0111 ^[33]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.15

Confidence interval

level

95%

sides

2-sided

lower limit

1.19

upper limit

3.88

Notes
[32] - Odds ratio of "3 mg BI 690517" vs. "Placebo to BI 690517".
[33] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[34]

P-value

= 0 ^[35]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.21

Confidence interval

level

95%

sides

2-sided

lower limit

2.88

upper limit

9.44

Notes
[34] - Odds ratio of "20 mg BI 690517" vs. "Placebo to BI 690517".
[35] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

10 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[36]

P-value

= 0 ^[37]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.33

Confidence interval

level

95%

sides

2-sided

lower limit

3.49

upper limit

11.49

Notes
[36] - Odds ratio of "10 mg BI 690517" vs. "Placebo to BI 690517".
[37] - P-value was rounded to four decimal places.

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 week - all patients - Last observation on treatment carried forward (LOCF)

Top of page

End point title

UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 week - all patients - Last observation on treatment carried forward (LOCF)

End point description

Number of patients with UACR response I is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. LOCF uses the last value observed on treatment to substitute all missing values until Week 14. This endpoint is reporting statistics for Full Analysis Set (FAS). FAS included all randomised patients to one of 3 doses of BI 690517 (3mg QD, 10 mg QD or 20 mg QD) or placebo matching BI 690517 who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6, 7 or 8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the last observation carried forward approach.

End point values	10 mg BI 690517	20 mg BI 690517	Placebo to BI 690517	BI 690517 3 mg
Number of subjects analysed	121	121	133	128
Units: Participants	67	73	31	45

Statistical analysis 1

Statistical analysis description

Comparison groups

BI 690517 3 mg v Placebo to BI 690517

Number of subjects included in analysis

261

Analysis specification

Pre-specified

Analysis type

other ^[38]

P-value

= 0.0348 ^[39]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

3.09

Notes
[38] - Odds ratio of "3 mg BI 690517" vs. "Placebo to BI 690517".
[39] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[40]

P-value

= 0 ^[41]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.02

Confidence interval

level

95%

sides

2-sided

lower limit

2.91

upper limit

8.67

Notes
[40] - Odds ratio of "20 mg BI 690517" vs. "Placebo to BI 690517".
[41] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

10 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[42]

P-value

= 0 ^[43]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.12

Confidence interval

level

95%

sides

2-sided

lower limit

2.4

upper limit

7.08

Notes
[42] - Odds ratio of "10 mg BI 690517" vs. "Placebo to BI 690517".
[43] - P-value was rounded to four decimal places.

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - complete case analysis

Top of page

End point title

UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - complete case analysis

End point description

Number of patients with UACR response I is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. Complete case analysis used patients with both baseline and Week 14 data available. All randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who had at least one baseline measurement of UACR at Week -2, -1, or 0 (i.e. Week 6, 7 or 8 of Run-in period) and one post-baseline measurement at Week 12-14 when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period.

End point values	3 mg BI 690517	10 mg BI 690517	20 mg BI 690517	Placebo to BI 690517
Number of subjects analysed	124	107	106	127
Units: Participants	40	62	57	23

Statistical analysis 1

Statistical analysis description

Comparison groups

3 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

251

Analysis specification

Pre-specified

Analysis type

other ^[44]

P-value

= 0.0111 ^[45]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.15

Confidence interval

level

95%

sides

2-sided

lower limit

1.19

upper limit

3.88

Notes
[44] - Odds ratio of "3 mg BI 690517" vs. "Placebo to BI 690517".
[45] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

10 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

234

Analysis specification

Pre-specified

Analysis type

other ^[46]

P-value

= 0 ^[47]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.33

Confidence interval

level

95%

sides

2-sided

lower limit

3.49

upper limit

11.49

Notes
[46] - Odds ratio of "10 mg BI 690517" vs. "Placebo to BI 690517".
[47] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

other ^[48]

P-value

= 0 ^[49]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.21

Confidence interval

level

95%

sides

2-sided

lower limit

2.88

upper limit

9.44

Notes
[48] - Odds ratio of "20 mg BI 690517" vs. "Placebo to BI 690517".
[49] - P-value was rounded to four decimal places.

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Multiple imputation

Top of page

End point title

UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Multiple imputation ^[50]

End point description

Number of patients with UACR response I for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. The multiple imputation filled in missing values at Week 14 based on other data observed in the same patient using regression. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo to BI 690517 who received placebo to empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6,7,8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo to BI 690517.

End point type

Secondary

End point timeframe

UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the multiple imputation approach.

Notes
[50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received placebo matching empagliflozin during the Run-in period.

End point values	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517
Number of subjects analysed	65	61	59	69
Units: Participants	19	31	30	10

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

other ^[51]

P-value

= 0.0419 ^[52]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.44

Confidence interval

level

95%

sides

2-sided

lower limit

1.03

upper limit

5.74

Notes
[51] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[52] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[53]

P-value

= 0 ^[54]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.13

Confidence interval

level

95%

sides

2-sided

lower limit

2.64

upper limit

14.25

Notes
[53] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[54] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other ^[55]

P-value

= 0 ^[56]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.09

Confidence interval

level

95%

sides

2-sided

lower limit

2.64

upper limit

14.08

Notes
[55] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[56] - P-value was rounded to four decimal places.

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Missing as non−responder

Top of page

End point title

End point description

Number of patients with UACR response I for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. The missing as non-responder imputes patients with missing Week 14 data as non-responders. This endpoint reports statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who received placebo to empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6,7,8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period.

Notes
[57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received placebo matching empagliflozin during the Run-in period.

End point values	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517
Number of subjects analysed	65	61	59	69
Units: Participants	19	28	25	9

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

other ^[58]

P-value

= 0.0195 ^[59]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.88

Confidence interval

level

95%

sides

2-sided

lower limit

1.19

upper limit

7.02

Notes
[58] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[59] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[60]

P-value

= 0.0001 ^[61]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.39

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

15.67

Notes
[60] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[61] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other ^[62]

P-value

= 0 ^[63]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.38

Confidence interval

level

95%

sides

2-sided

lower limit

2.65

upper limit

15.35

Notes
[62] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[63] - P-value was rounded to four decimal places.

Secondary: UACR response I, defined as decrease of at least 30% absolute change in FMV urine of UACR from treatment period baseline to 14 weeks - background therapy of placebo matching empagliflozin - Last observation on treatment carried forward (LOCF)

Top of page

End point title

UACR response I, defined as decrease of at least 30% absolute change in FMV urine of UACR from treatment period baseline to 14 weeks - background therapy of placebo matching empagliflozin - Last observation on treatment carried forward (LOCF) ^[64]

End point description

Number of patients with UACR response I for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void (FMV) urine of UACR from treatment period baseline to 14 weeks. LOCF uses the last value observed on treatment to substitute all missing values until Week 14. This endpoint reports statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who received placebo to empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6,7,8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the last observation carried forward approach.

Notes
[64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received placebo matching empagliflozin during the Run-in period.

End point values	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517
Number of subjects analysed	65	61	59	69
Units: Participants	22	31	32	14

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

other ^[65]

P-value

= 0.0767 ^[66]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

4.42

Notes
[65] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[66] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[67]

P-value

= 0.0001 ^[68]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.69

Confidence interval

level

95%

sides

2-sided

lower limit

2.15

upper limit

10.24

Notes
[67] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[68] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other ^[69]

P-value

= 0.0003 ^[70]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.11

Confidence interval

level

95%

sides

2-sided

lower limit

1.89

upper limit

8.91

Notes
[69] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[70] - P-value was rounded to four decimal places.

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - complete case analysis

Top of page

End point title

End point description

Number of patients with UACR response I for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. Complete case analysis used patients with both baseline and Week 14 data available. This endpoint reports statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who had received placebo matching empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (i.e. Week 6, 7 or 8 of Run-in period) and one post-baseline measurement at Week 12-14 when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period.

Notes
[71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received placebo matching empagliflozin during the Run-in period.

End point values	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517
Number of subjects analysed	61	56	50	66
Units: Participants	19	28	25	9

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

other ^[72]

P-value

= 0.0195 ^[73]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.88

Confidence interval

level

95%

sides

2-sided

lower limit

1.19

upper limit

7.02

Notes
[72] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[73] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

other ^[74]

P-value

= 0.0001 ^[75]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.39

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

15.67

Notes
[74] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[75] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517 v Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

other ^[76]

P-value

= 0 ^[77]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.38

Confidence interval

level

95%

sides

2-sided

lower limit

2.65

upper limit

15.35

Notes
[76] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[77] - P-value was rounded to four decimal places.

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Multiple imputation

Top of page

End point title

End point description

Number of patients with UACR response I for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. The multiple imputation filled in missing values at Week 14 based on other data observed in the same patient using regression. This endpoint reports statistics for all randomised patients to of 3 doses of BI 690517 or placebo matching BI 690517 who received empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6,7,8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 placebo matching BI 690517.

End point type

Secondary

End point timeframe

UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the multiple imputation approach.

Notes
[78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received empagliflozin during the Run-in period.

End point values	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517
Number of subjects analysed	63	60	62	64
Units: Participants	21	42	36	14

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 3 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

other ^[79]

P-value

= 0.1398 ^[80]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

4.04

Notes
[79] - Odds ratio of "Treatment period: 10 mg Empa+ 3 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[80] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 10 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

other ^[81]

P-value

= 0 ^[82]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

8.42

Confidence interval

level

95%

sides

2-sided

lower limit

3.73

upper limit

19.02

Notes
[81] - Odds ratio of "Treatment period: 10 mg Empa + 10 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[82] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 20 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other ^[83]

P-value

= 0.0001 ^[84]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.98

Confidence interval

level

95%

sides

2-sided

lower limit

2.28

upper limit

10.9

Notes
[83] - P-value was rounded to four decimal places.
[84] - Odds ratio of "Treatment period: 10 mg Empa + 20 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Missing as non−responder

Top of page

End point title

End point description

Number of patients with UACR response I for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. The missing as non-responder imputes patients with missing Week 14 data as non-responders. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who received empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6,7,8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period.

Notes
[85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received empagliflozin during the Run-in period.

End point values	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517
Number of subjects analysed	63	60	62	64
Units: Participants	21	34	32	14

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 3 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

other ^[86]

P-value

= 0.1884 ^[87]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

3.79

Notes
[86] - Odds ratio of "Treatment period: 10 mg Empa + 3 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[87] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 20 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other ^[88]

P-value

= 0.0003 ^[89]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.46

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

9.94

Notes
[88] - Odds ratio of "Treatment period: 10 mg Empa + 20 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[89] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 10 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

other ^[90]

P-value

= 0 ^[91]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.8

Confidence interval

level

95%

sides

2-sided

lower limit

2.94

upper limit

15.72

Notes
[90] - Odds ratio of "Treatment period: 10 mg Empa + 10 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[91] - P-value was rounded to four decimal places.

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - complete case analysis

Top of page

End point title

End point description

Number of patients with UACR response I for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. Complete case analysis used patients with both baseline and Week 14 data available. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who had received empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (i.e. Week 6, 7 or 8 of Run-in period) and one post-baseline measurement at Week 12-14 when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period.

Notes
[92] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received empagliflozin during the Run-in period.

End point values	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517
Number of subjects analysed	63	51	56	61
Units: Participants	21	34	32	14

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 3 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

other ^[93]

P-value

= 0.1884 ^[94]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

3.79

Notes
[93] - Odds ratio of "Treatment period: 10 mg Empa + 3 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[94] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 10 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

other ^[95]

P-value

= 0 ^[96]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.8

Confidence interval

level

95%

sides

2-sided

lower limit

2.94

upper limit

15.72

Notes
[95] - Odds ratio of "Treatment period: 10 mg Empa + 10 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[96] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 20 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

other ^[97]

P-value

= 0.0003 ^[98]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.46

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

9.94

Notes
[97] - Odds ratio of "Treatment period: 10 mg Empa+ 20 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[98] - P-value was rounded to four decimal places.

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients -multiple imputation

Top of page

End point title

UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients -multiple imputation

End point description

Number of patients with UACR response II is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 week. The multiple imputation filled in missing values at Week 14 based on other data observed in the same patient using regression. This endpoint is reporting statistics for the Full Analysis Set (FAS). FAS included all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6, 7 or 8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the multiple imputation approach.

End point values	3 mg BI 690517	10 mg BI 690517	20 mg BI 690517	Placebo to BI 690517
Number of subjects analysed	128	121	121	133
Units: Participants	68	82	81	46

Statistical analysis 1

Statistical analysis description

Comparison groups

3 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

261

Analysis specification

Pre-specified

Analysis type

other ^[99]

P-value

= 0.0024 ^[100]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.18

Confidence interval

level

95%

sides

2-sided

lower limit

1.32

upper limit

3.61

Notes
[99] - Odds ratio of "3 mg BI 690517" vs. "Placebo to BI 690517".
[100] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[101]

P-value

= 0 ^[102]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.87

Confidence interval

level

95%

sides

2-sided

lower limit

2.29

upper limit

6.55

Notes
[101] - Odds ratio of "20 mg BI 690517" vs. "Placebo to BI 690517".
[102] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

10 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[103]

P-value

= 0 ^[104]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.05

Confidence interval

level

95%

sides

2-sided

lower limit

2.39

upper limit

6.86

Notes
[103] - Odds ratio of "10 mg BI 690517" vs. "Placebo to BI 690517".
[104] - P-value was rounded to four decimal places.

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Missing as non−responder

Top of page

End point title

UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Missing as non−responder

End point description

Number of patients with UACR response II is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. The missing as non-responder imputes patients with missing Week 14 data as non-responders. This endpoint is reporting statistics for the Full Analysis Set (FAS). FAS included all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6, 7 or 8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period.

End point values	3 mg BI 690517	10 mg BI 690517	20 mg BI 690517	Placebo to BI 690517
Number of subjects analysed	128	121	121	133
Units: Participants	67	71	70	44

Statistical analysis 1

Statistical analysis description

Comparison groups

3 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

261

Analysis specification

Pre-specified

Analysis type

other ^[105]

P-value

= 0.0019 ^[106]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.26

Confidence interval

level

95%

sides

2-sided

lower limit

1.35

upper limit

3.77

Notes
[105] - Odds ratio of "3 mg BI 690517" vs. "Placebo to BI 690517".
[106] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[107]

P-value

= 0 ^[108]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.67

Confidence interval

level

95%

sides

2-sided

lower limit

2.12

upper limit

6.35

Notes
[107] - Odds ratio of "20 mg BI 690517" vs. "Placebo to BI 690517".
[108] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

10 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[109]

P-value

= 0 ^[110]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.81

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

6.59

Notes
[109] - Odds ratio of "10 mg BI 690517" vs. "Placebo to BI 690517"
[110] - P-value was rounded to four decimal places.

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Last observation on treatment carried forward (LOCF)

Top of page

End point title

UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Last observation on treatment carried forward (LOCF)

End point description

Number of patients with UACR response II is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. LOCF uses the last value observed on treatment to substitute all missing values until Week 14. This endpoint is reporting statistics for Full Analysis Set (FAS). FAS included all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6, 7 or 8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the last observation carried forward approach.

End point values	3 mg BI 690517	10 mg BI 690517	20 mg BI 690517	Placebo to BI 690517
Number of subjects analysed	128	121	121	133
Units: Participants	67	87	85	53

Statistical analysis 1

Statistical analysis description

Comparison groups

3 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

261

Analysis specification

Pre-specified

Analysis type

other ^[111]

P-value

= 0.0418 ^[112]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.67

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

2.74

Notes
[111] - Odds ratio of "3 mg BI 690517" vs. "Placebo to BI 690517".
[112] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[113]

P-value

= 0 ^[114]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.58

Confidence interval

level

95%

sides

2-sided

lower limit

2.11

upper limit

6.05

Notes
[113] - Odds ratio of "20 mg BI 690517" vs. "Placebo to BI 690517".
[114] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

10 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[115]

P-value

= 0 ^[116]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.91

Confidence interval

level

95%

sides

2-sided

lower limit

2.3

upper limit

6.65

Notes
[115] - Odds ratio of "10 mg BI 690517" vs. "Placebo to BI 690517".
[116] - P-value was rounded to four decimal places.

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - complete case analysis

Top of page

End point title

UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - complete case analysis

End point description

Number of patients with UACR response II is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. Complete case analysis used patients with both baseline and Week 14 data available. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who had at least one baseline measurement of UACR at Week -2, -1, or 0 (i.e. Week 6, 7 or 8 of Run-in period) and one post-baseline measurement at Week 12-14 when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period.

End point values	3 mg BI 690517	10 mg BI 690517	20 mg BI 690517	Placebo to BI 690517
Number of subjects analysed	124	107	106	127
Units: Participants	67	71	70	44

Statistical analysis 1

Statistical analysis description

Comparison groups

3 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

251

Analysis specification

Pre-specified

Analysis type

other ^[117]

P-value

= 0.0019 ^[118]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.26

Confidence interval

level

95%

sides

2-sided

lower limit

1.35

upper limit

3.77

Notes
[117] - Odds ratio of "3 mg BI 690517" vs. "Placebo to BI 690517".
[118] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

20 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

other ^[119]

P-value

= 0 ^[120]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.67

Confidence interval

level

95%

sides

2-sided

lower limit

2.12

upper limit

6.35

Notes
[119] - Odds ratio of "20 mg BI 690517" vs. "Placebo to BI 690517".
[120] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

10 mg BI 690517 v Placebo to BI 690517

Number of subjects included in analysis

234

Analysis specification

Pre-specified

Analysis type

other ^[121]

P-value

= 0 ^[122]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.81

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

6.59

Notes
[121] - Odds ratio of "10 mg BI 690517" vs. "Placebo to BI 690517".
[122] - P-value was rounded to four decimal places.

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Multiple imputation

Top of page

End point title

UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Multiple imputation ^[123]

End point description

Number of patients with UACR response II for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. The multiple imputation filled in missing values at Week 14 based on other data observed in the same patient using regression. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo to BI 690517 who received placebo to empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6,7,8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo to BI 690517.

End point type

Secondary

End point timeframe

UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the multiple imputation approach.

Notes
[123] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received placebo matching empagliflozin during the Run-in period.

End point values	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517
Number of subjects analysed	65	61	59	69
Units: Participants	33	35	39	22

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

other ^[124]

P-value

= 0.0285 ^[125]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

4.45

Notes
[124] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[125] - P-value was rounded to four decimal places.

Statistica analysis 3

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[126]

P-value

= 0.0002 ^[127]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.15

Confidence interval

level

95%

sides

2-sided

lower limit

1.97

upper limit

8.72

Notes
[126] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[127] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other ^[128]

P-value

= 0.0038 ^[129]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

1.41

upper limit

5.96

Notes
[128] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[129] - P-value was rounded to four decimal places.

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Missing as non−responder

Top of page

End point title

End point description

Number of patients with UACR response II for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. The missing as non-responder imputes patients with missing Week 14 data as non-responders. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who received placebo to empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6,7,8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period.

Notes
[130] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received placebo matching empagliflozin during the Run-in period.

End point values	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517
Number of subjects analysed	65	61	59	69
Units: Participants	32	32	32	20

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

other ^[131]

P-value

= 0.0116 ^[132]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.56

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

5.31

Notes
[131] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[132] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[133]

P-value

= 0.0004 ^[134]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.07

Confidence interval

level

95%

sides

2-sided

lower limit

1.86

upper limit

8.91

Notes
[133] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[134] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other ^[135]

P-value

= 0.0032 ^[136]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.08

Confidence interval

level

95%

sides

2-sided

lower limit

1.46

upper limit

6.52

Notes
[135] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[136] - P-value was rounded to four decimal places.

Secondary: UACR response II, defined as decrease of at least 15% absolute change in FMV urine of UACR from treatment period baseline to 14 weeks - background therapy of placebo matching empagliflozin - Last observation on treatment carried forward (LOCF)

Top of page

End point title

UACR response II, defined as decrease of at least 15% absolute change in FMV urine of UACR from treatment period baseline to 14 weeks - background therapy of placebo matching empagliflozin - Last observation on treatment carried forward (LOCF) ^[137]

End point description

Number of patients with UACR response II for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void (FMV) urine of UACR from treatment period baseline to 14 weeks. LOCF uses the last value observed on treatment to substitute all missing values until Week 14. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who received placebo to empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6,7,8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the last observation carried forward approach.

Notes
[137] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received placebo matching empagliflozin during the Run-in period.

End point values	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517
Number of subjects analysed	65	61	59	69
Units: Participants	28	41	41	25

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

other ^[138]

P-value

= 0.4092 ^[139]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.34

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

2.69

Notes
[138] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[139] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[140]

P-value

= 0.0002 ^[141]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.04

Confidence interval

level

95%

sides

2-sided

lower limit

1.92

upper limit

8.49

Notes
[140] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[141] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other ^[142]

P-value

= 0.0005 ^[143]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.66

Confidence interval

level

95%

sides

2-sided

lower limit

1.77

upper limit

7.58

Notes
[142] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[143] - P-value was rounded to four decimal places.

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Multiple imputation

Top of page

End point title

End point description

Number of patients with UACR response II for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. The multiple imputation filled in missing values at Week 14 based on other data observed in the same patient using regression. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who received empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6,7,8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the multiple imputation approach.

Notes
[144] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received empagliflozin during the Run-in period.

End point values	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517
Number of subjects analysed	63	60	62	64
Units: Participants	35	47	42	24

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 3 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

other ^[145]

P-value

= 0.0348 ^[146]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.16

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

4.43

Notes
[145] - Odds ratio of "Treatment period: 10 mg Empa + 3 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[146] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 10 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

other ^[147]

P-value

= 0 ^[148]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.08

Confidence interval

level

95%

sides

2-sided

lower limit

2.73

upper limit

13.57

Notes
[147] - Odds ratio of "Treatment period: 10 mg Empa + 10 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[148] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 20 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other ^[149]

P-value

= 0.0007 ^[150]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.58

Confidence interval

level

95%

sides

2-sided

lower limit

1.71

upper limit

7.52

Notes
[149] - Odds ratio of "Treatment period: 10 mg Empa + 20 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[150] - P-value was rounded to four decimal places.

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Missing as non−responder

Top of page

End point title

End point description

Number of patients with UACR response II for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. The missing as non-responder imputes patients with missing Week 14 data as non-responders. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who received empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6,7,8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period.

Notes
[151] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received empagliflozin during the Run-in period.

End point values	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517
Number of subjects analysed	63	60	62	64
Units: Participants	35	39	38	24

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 3 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

other ^[152]

P-value

= 0.0578 ^[153]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

4.14

Notes
[152] - Odds ratio of "Treatment period: 10 mg Empa + 3 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[153] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 20 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other ^[154]

P-value

= 0.0022 ^[155]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.32

Confidence interval

level

95%

sides

2-sided

lower limit

1.54

upper limit

7.16

Notes
[154] - Odds ratio of "Treatment period: 10 mg Empa + 20 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[155] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 10 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

other ^[156]

P-value

= 0.0001 ^[157]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.12

Confidence interval

level

95%

sides

2-sided

lower limit

2.23

upper limit

11.78

Notes
[156] - Odds ratio of "Treatment period: 10 mg Empa + 10 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[157] - P-value was rounded to four decimal places.

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks -patients with background therapy of placebo matching empagliflozin - complete case analysis

Top of page

End point title

UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks -patients with background therapy of placebo matching empagliflozin - complete case analysis ^[158]

End point description

Number of patients with UACR response II for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. Complete case analysis used patients with both baseline and Week 14 data available. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who had received placebo matching empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (i.e. Week 6, 7 or 8 of Run-in period) and one post-baseline measurement at Week 12-14 when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period.

Notes
[158] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received placebo matching empagliflozin during the Run-in period.

End point values	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517
Number of subjects analysed	61	56	50	66
Units: Participants	32	32	32	20

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

other ^[159]

P-value

= 0.0116 ^[160]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.56

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

5.31

Notes
[159] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[160] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

other ^[161]

P-value

= 0.0004 ^[162]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.07

Confidence interval

level

95%

sides

2-sided

lower limit

1.86

upper limit

8.91

Notes
[161] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[162] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517 v Treatment period: Placebo to Empa 10 mg+Placebo to BI 690517

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

other ^[163]

P-value

= 0.0032 ^[164]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.08

Confidence interval

level

95%

sides

2-sided

lower limit

1.46

upper limit

6.52

Notes
[163] - Odds ratio of "Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517" vs. "Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517".
[164] - P-value was rounded to four decimal places.

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - complete case analysis

Top of page

End point title

End point description

Number of patients with UACR response II for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. Complete case analysis used patients with both baseline and Week 14 data available. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who had received empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (i.e. Week 6, 7 or 8 of Run-in period) and post-baseline measurement at Week 12-14 when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period.

Notes
[165] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received empagliflozin during the Run-in period.

End point values	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517
Number of subjects analysed	63	51	56	61
Units: Participants	35	39	38	24

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 3 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

other ^[166]

P-value

= 0.0578 ^[167]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

4.14

Notes
[166] - Odds ratio of "Treatment period: 10 mg Empa + 3 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[167] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 20 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

other ^[168]

P-value

= 0.0022 ^[169]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.32

Confidence interval

level

95%

sides

2-sided

lower limit

1.54

upper limit

7.16

Notes
[168] - Odds ratio of "Treatment period: 10 mg Empa + 20 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[169] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 10 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

other ^[170]

P-value

= 0.0001 ^[171]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.12

Confidence interval

level

95%

sides

2-sided

lower limit

2.23

upper limit

11.78

Notes
[170] - Odds ratio of "Treatment period: 10 mg Empa + 10 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[171] - P-value was rounded to four decimal places.

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Last observation on treatment carried forward

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End point title

UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Last observation on treatment carried forward ^[172]

End point description

Number of patients with UACR response I for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. Last observation on treatment carried forward (LOCF) uses the last value observed on treatment to substitute all missing values until Week 14. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who received empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6,7,8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the last observation carried forward approach.

Notes
[172] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received empagliflozin during the Run-in period.

End point values	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517
Number of subjects analysed	63	60	62	64
Units: Participants	23	36	41	17

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 3 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

other ^[173]

P-value

= 0.214 ^[174]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

3.46

Notes
[173] - Odds ratio of "Treatment period: 10 mg Empa + 3 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[174] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 20 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other ^[175]

P-value

= 0 ^[176]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.43

Confidence interval

level

95%

sides

2-sided

lower limit

2.52

upper limit

11.71

Notes
[175] - Odds ratio of "Treatment period: 10 mg Empa + 20 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[176] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 10 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

other ^[177]

P-value

= 0.0003 ^[178]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.13

Confidence interval

level

95%

sides

2-sided

lower limit

1.93

upper limit

8.85

Notes
[177] - Odds ratio of "Treatment period: 10 mg Empa + 10 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[178] - P-value was rounded to four decimal places.

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Last observation on treatment carried forward

Top of page

End point title

UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Last observation on treatment carried forward ^[179]

End point description

Number of patients with UACR response II for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks. Last observation on treatment carried forward (LOCF) uses the last value observed on treatment to substitute all missing values until Week 12-14. This endpoint is reporting statistics for all randomised patients to one of 3 doses of BI 690517 or placebo matching BI 690517 who received empagliflozin during the Run-in Period and who had at least one baseline measurement of UACR at Week -2, -1, or 0 (Week 6,7,8 of the Run-in Period) and at least one post-baseline measurement when patients were still on treatment with BI 690517 or placebo matching BI 690517.

End point type

Secondary

End point timeframe

UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the last observation carried forward approach.

Notes
[179] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reporting statistics only for the patients who received empagliflozin during the Run-in period.

End point values	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517
Number of subjects analysed	63	60	62	64
Units: Participants	39	46	44	28

Statistical analysis 1

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 3 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

other ^[180]

P-value

= 0.0342 ^[181]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.17

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

4.44

Notes
[180] - Odds ratio of "Treatment period: 10 mg Empa + 3 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[181] - P-value was rounded to four decimal places.

Statistical analysis 3

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 20 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other ^[182]

P-value

= 0.0023 ^[183]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.19

Confidence interval

level

95%

sides

2-sided

lower limit

1.52

upper limit

6.73

Notes
[182] - Odds ratio of "Treatment period: 10 mg Empa + 20 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[183] - P-value was rounded to four decimal places.

Statistical analysis 2

Statistical analysis description

Comparison groups

Treatment period: 10 mg Empa + 10 mg BI 690517 v Treatment period: 10 mg Empa + Placebo to BI 690517

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

other ^[184]

P-value

= 0.0003 ^[185]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.23

Confidence interval

level

95%

sides

2-sided

lower limit

1.93

upper limit

9.24

Notes
[184] - Odds ratio of "Treatment period: 10 mg Empa + 10 mg BI 690517" vs. "Treatment period: 10 mg Empa + Placebo to BI 690517".
[185] - P-value was rounded to four decimal places.

Adverse events

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Timeframe for reporting adverse events

From first study drug administration in the treatment period until end of the residual effect period (i.e. 7 days for empagliflozin and BI 690517), up to 15 weeks.

Adverse event reporting additional description

Adverse events were planned in the protocol and statistical analysis plan to be reported for the treated set. Treated Set (TS): This patient set included all patients who received at least one dose of BI 690517 or placebo matching BI 690517.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

Treatment period: 10 mg Empa + 3 mg BI 690517

Reporting group description

Reporting group title

Treatment period: 10 mg Empa + 20 mg BI 690517

Reporting group description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 20 milligrams (mg) of BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received 20 mg BI 690517 and 10 mg empagliflozin for 14 weeks.

Reporting group title

Treatment period: 10 mg Empa + 10 mg BI 690517

Reporting group description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 10 milligrams (mg) of BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received 10 mg BI 690517 and 10 mg empagliflozin for 14 weeks.

Reporting group title

Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517

Reporting group description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 20 mg of BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received 20 mg BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Reporting group title

Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517

Reporting group description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received 10 mg of BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received 10 mg BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Reporting group title

Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517

Reporting group description

Reporting group title

Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517

Reporting group description

This arm includes patients who received placebo matching empagliflozin (Empa) 10 milligrams (mg) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received placebo matching BI 690517 once daily (QD) orally in combination with placebo matching empagliflozin 10 mg QD orally. Patients received placebo matching BI 690517 and placebo matching empagliflozin 10 mg for 14 weeks.

Reporting group title

Treatment period: 10 mg Empa + Placebo to BI 690517

Reporting group description

This arm includes patients who received 10 mg of empagliflozin (Empa) during the run-in period and met the eligibility criteria to enter the treatment period. In the treatment period patients received placebo matching BI 690517 once daily (QD) orally in combination with 10 mg of empagliflozin QD orally. Patients received placebo matching BI 690517 and 10 mg empagliflozin for 14 weeks.

Serious adverse events	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 76 (5.26%)	5 / 74 (6.76%)	7 / 73 (9.59%)	6 / 72 (8.33%)	4 / 71 (5.63%)	3 / 70 (4.29%)	3 / 73 (4.11%)	7 / 74 (9.46%)
number of deaths (all causes)	1	0	1	1	1	0	0	2
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon
subjects affected / exposed	1 / 76 (1.32%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of lung
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	1 / 74 (1.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transitional cell carcinoma metastatic
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Aortic thrombosis
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	1 / 72 (1.39%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coeliac artery occlusion
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	1 / 72 (1.39%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Phlebitis
subjects affected / exposed	1 / 76 (1.32%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Sudden death
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	1 / 71 (1.41%)	0 / 70 (0.00%)	0 / 73 (0.00%)	1 / 74 (1.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	1 / 73 (1.37%)	1 / 74 (1.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	1 / 76 (1.32%)	0 / 74 (0.00%)	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	1 / 73 (1.37%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Haematuria traumatic
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	1 / 73 (1.37%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac failure
subjects affected / exposed	1 / 76 (1.32%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	1 / 73 (1.37%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	1 / 73 (1.37%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	1 / 70 (1.43%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive heart disease
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intracardiac thrombus
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	1 / 72 (1.39%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebral infarction
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	1 / 72 (1.39%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dizziness
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	1 / 72 (1.39%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic cerebral infarction
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	1 / 71 (1.41%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	1 / 74 (1.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	1 / 72 (1.39%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	1 / 72 (1.39%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombosis mesenteric vessel
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	1 / 72 (1.39%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Diabetic foot
subjects affected / exposed	0 / 76 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	2 / 72 (2.78%)	1 / 71 (1.41%)	0 / 70 (0.00%)	1 / 73 (1.37%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 2	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Focal segmental glomerulosclerosis
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	1 / 74 (1.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal artery stenosis
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhage urinary tract
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	1 / 73 (1.37%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal mass
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subcapsular renal haematoma
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	1 / 70 (1.43%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 76 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)	2 / 72 (2.78%)	0 / 71 (0.00%)	1 / 70 (1.43%)	0 / 73 (0.00%)	1 / 74 (1.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 2	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Glucocorticoid deficiency
subjects affected / exposed	1 / 76 (1.32%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess soft tissue
subjects affected / exposed	0 / 76 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	1 / 74 (1.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dengue fever
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	1 / 71 (1.41%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	1 / 76 (1.32%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	1 / 74 (1.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 76 (1.32%)	0 / 74 (0.00%)	1 / 73 (1.37%)	0 / 72 (0.00%)	1 / 71 (1.41%)	0 / 70 (0.00%)	1 / 73 (1.37%)	1 / 74 (1.35%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	1 / 71 (1.41%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 76 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	1 / 72 (1.39%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus inadequate control
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	1 / 73 (1.37%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	0 / 76 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 76 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)	1 / 72 (1.39%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolic syndrome
subjects affected / exposed	0 / 76 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 71 (0.00%)	0 / 70 (0.00%)	0 / 73 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Treatment period: 10 mg Empa + 3 mg BI 690517	Treatment period: 10 mg Empa + 20 mg BI 690517	Treatment period: 10 mg Empa + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 20 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 10 mg BI 690517	Treatment period: Placebo to Empa 10 mg + 3 mg BI 690517	Treatment period: Placebo to Empa 10 mg + Placebo to BI 690517	Treatment period: 10 mg Empa + Placebo to BI 690517
Total subjects affected by non serious adverse events
subjects affected / exposed	11 / 76 (14.47%)	19 / 74 (25.68%)	20 / 73 (27.40%)	25 / 72 (34.72%)	16 / 71 (22.54%)	15 / 70 (21.43%)	9 / 73 (12.33%)	13 / 74 (17.57%)
Investigations
Cortisol decreased
subjects affected / exposed	2 / 76 (2.63%)	0 / 74 (0.00%)	1 / 73 (1.37%)	2 / 72 (2.78%)	4 / 71 (5.63%)	3 / 70 (4.29%)	0 / 73 (0.00%)	1 / 74 (1.35%)
occurrences all number	2	0	1	2	4	3	0	1
Glomerular filtration rate decreased
subjects affected / exposed	4 / 76 (5.26%)	7 / 74 (9.46%)	8 / 73 (10.96%)	6 / 72 (8.33%)	7 / 71 (9.86%)	1 / 70 (1.43%)	3 / 73 (4.11%)	2 / 74 (2.70%)
occurrences all number	4	7	8	6	7	1	4	2
Vascular disorders
Hypotension
subjects affected / exposed	0 / 76 (0.00%)	2 / 74 (2.70%)	4 / 73 (5.48%)	0 / 72 (0.00%)	0 / 71 (0.00%)	1 / 70 (1.43%)	0 / 73 (0.00%)	1 / 74 (1.35%)
occurrences all number	0	2	4	0	0	1	0	1
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	1 / 76 (1.32%)	4 / 74 (5.41%)	1 / 73 (1.37%)	3 / 72 (4.17%)	1 / 71 (1.41%)	2 / 70 (2.86%)	2 / 73 (2.74%)	4 / 74 (5.41%)
occurrences all number	1	4	1	5	1	2	2	5
Metabolism and nutrition disorders
Hyperkalaemia
subjects affected / exposed	5 / 76 (6.58%)	7 / 74 (9.46%)	11 / 73 (15.07%)	17 / 72 (23.61%)	7 / 71 (9.86%)	8 / 70 (11.43%)	4 / 73 (5.48%)	5 / 74 (6.76%)
occurrences all number	5	7	11	20	8	8	6	10

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

25 Oct 2021

Global protocol amendment 1 included the following changes in the protocol. The screening period was extended from 14 to 21 days to allow for any allowed repetition of screening procedures. The Flowchart was changed to detect and mitigate the potential risk of adrenal insufficiency by addition of extensive serum and urine cortisol sampling and addition of an adrenocorticotropic hormone (ACTH) challenge test (on an as-needed basis based on cortisol levels); serum cortisol was added to the list of hormones to be tested in safety laboratory parameters. The Flowchart was changed to allow pre-screening for urine albumin creatinine ratio (UACR) and estimated Glomerular Filtration Rate (eGFR) subject to pre-screening informed consent. Legal adult age (according to local legislation) as part of the inclusion criteria was added on top of 18+ years of age. Patients who needed to or wished to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial were excluded. An exclusionary criterion regarding intake biotin or related preparations was introduced. Patients who had taken Vitamin B7, Vitamin H, or coenzyme-R at doses ≥5 mg/day (including food supplements) within 72 h of Visit 1 or who planned to take above dosesof biotin during the trial were excluded. The original cut off value of increase in serum cortisol of 200 nmol/L at 30 min postinjection was modified to absolute cortisol value of <18 μg/dL (496.6 nmol/L) at 30 min (± 5 min) after injection of ACTH at Visit 1 to follow the Cosyntropin label and relevant United States (US) guidelines. Any clinically relevant abnormal laboratory value was expanded to specifically include a serum cortisol level <5 μg/dL (138.0 nmol/L) at Visit 1 or until first randomization to exclude those patients at greater risk of adrenal insufficiency.

25 Oct 2021

Global protocol amendment 1 continued: Added requirements for discontinuation of trial treatment (BI 690517/placebo) in patients who develop Cushing’s syndrome, adrenal insufficiency (including cortisol level <18 μg/dL 30 min (±5 min) after ACTH application), or cortisol levels <3 μg/dL (82.8 nmol/L) at any point in the trial should. Added requirement to permanently discontinue patients who permanently discontinue empagliflozin/placebo during the randomised run-in period due to any reason. Adrenal insufficiency and Cushing’s syndrome were added as an AESI to the protocol. Requirements for ACTH challenge tests during the study and at the end of treatment were added. The shipment of trial medication from the site to the patient’s home was allowed to support regular visits performed at the patient’s home specified by the Flowchart. Management of eGFR decrease was specified. Management of serum cortisol decrease was specified.

30 Mar 2022

Global protocol amendment 2 included the following changes. Flowchart was modified to remove 24-hour urine sample at EOT for patients who discontinue prematurely before initiation of treatment with BI 690517/placebo. Inclusion criteria on chronic kidney disease as baseline condition was simplified to include patients with any kind of diagnosed chronic kidney disease according to Investigator’s opinion and that diagnosis of chronic kidney disease (CKD) could be reached by standard clinical method and no biopsy was required. An additional criterion mandating screening of patients before the second randomization to treatment period was added to exclude patients with known hepatic cirrhosis (Child Pugh A, B or C), or other liver disease causing impaired liver function according to investigator’s judgement. An additional criterion was added to exclude those patients with CKD in whom no benefit to treatment with BI 690517 was expected due to underlying causes of CKD attributed to either of the following: CKD secondary due to malignancy (e.g. Cast-Nephropathy, AL-amyloidosis), CKD secondary to infectious disease (e.g. Hepatitis-/HIV-associated), autosomal-dominant polycystic kidney disease. Clarification was provided regarding unblinding status at last patient last visit primary endpoint snapshot. Methotrexate was added to the restricted medications list.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: Randomised, double-blind, placebo-controlled and parallel dose group trial to investigate efficacy and safety of multiple doses of oral BI 690517 over 14 weeks, alone and in combination with empagliflozin, in patients with diabetic and non-diabetic chronic kidney disease

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from treatment period baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in First Morning Void (FMV) urine after 14 weeks - all patients

Primary: Change from treatment period baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in First Morning Void (FMV) urine after 14 weeks - all patients

Primary: Percent change of FMV UACR from baseline to Week 14 based on adjusted median (95% CI) back transformed from MMRM estimate - all patients

Primary: Percent change of FMV UACR from baseline to Week 14 based on adjusted median (95% CI) back transformed from MMRM estimate - all patients

Primary: Change from baseline to Week 14 in the log transformed FMV UACR − patients with background therapy of placebo matching empagliflozin

Primary: Change from baseline to Week 14 in the log transformed FMV UACR − patients with background therapy of placebo matching empagliflozin

Primary: Percent change of FMV UACR from baseline to Week 14 based on adjusted median (95% CI) back transformed from MMRM estimate − patients with background therapy of placebo matching empagliflozin

Primary: Percent change of FMV UACR from baseline to Week 14 based on adjusted median (95% CI) back transformed from MMRM estimate − patients with background therapy of placebo matching empagliflozin

Primary: Change from baseline to Week 14 in the log transformed FMV UACR − patients with background therapy of empagliflozin

Primary: Change from baseline to Week 14 in the log transformed FMV UACR − patients with background therapy of empagliflozin

Primary: Percent change of FMV UACR from baseline to Week 14 based on adjusted median (95% CI) of MMRM estimate − patients with background therapy of empagliflozin

Primary: Percent change of FMV UACR from baseline to Week 14 based on adjusted median (95% CI) of MMRM estimate − patients with background therapy of empagliflozin

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Multiple imputation

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Multiple imputation

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Missing as non−responder

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Missing as non−responder

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 week - all patients - Last observation on treatment carried forward (LOCF)

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 week - all patients - Last observation on treatment carried forward (LOCF)

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - complete case analysis

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - complete case analysis

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Multiple imputation

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Multiple imputation

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Missing as non−responder

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Missing as non−responder

Secondary: UACR response I, defined as decrease of at least 30% absolute change in FMV urine of UACR from treatment period baseline to 14 weeks - background therapy of placebo matching empagliflozin - Last observation on treatment carried forward (LOCF)

Secondary: UACR response I, defined as decrease of at least 30% absolute change in FMV urine of UACR from treatment period baseline to 14 weeks - background therapy of placebo matching empagliflozin - Last observation on treatment carried forward (LOCF)

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - complete case analysis

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - complete case analysis

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Multiple imputation

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Multiple imputation

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Missing as non−responder

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Missing as non−responder

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - complete case analysis

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - complete case analysis

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients -multiple imputation

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients -multiple imputation

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Missing as non−responder

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Missing as non−responder

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Last observation on treatment carried forward (LOCF)

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - Last observation on treatment carried forward (LOCF)

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - complete case analysis

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - all patients - complete case analysis

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Multiple imputation

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Multiple imputation

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Missing as non−responder

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of placebo matching empagliflozin - Missing as non−responder

Secondary: UACR response II, defined as decrease of at least 15% absolute change in FMV urine of UACR from treatment period baseline to 14 weeks - background therapy of placebo matching empagliflozin - Last observation on treatment carried forward (LOCF)

Secondary: UACR response II, defined as decrease of at least 15% absolute change in FMV urine of UACR from treatment period baseline to 14 weeks - background therapy of placebo matching empagliflozin - Last observation on treatment carried forward (LOCF)

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Multiple imputation

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Multiple imputation

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Missing as non−responder

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Missing as non−responder

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks -patients with background therapy of placebo matching empagliflozin - complete case analysis

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks -patients with background therapy of placebo matching empagliflozin - complete case analysis

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - complete case analysis

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - complete case analysis

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Last observation on treatment carried forward

Secondary: UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Last observation on treatment carried forward

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Last observation on treatment carried forward

Secondary: UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks - patients with background therapy of empagliflozin - Last observation on treatment carried forward

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
Randomised, double-blind, placebo-controlled and parallel dose group trial to investigate efficacy and safety of multiple doses of oral BI 690517 over 14 weeks, alone and in combination with empagliflozin, in patients with diabetic and non-diabetic chronic kidney disease