| CTRI Number |
CTRI/2022/03/041244 [Registered on: 22/03/2022] Trial Registered Prospectively |
| Last Modified On: |
07/06/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
A study to test whether different doses of BI 690517 alone or in combination with empagliflozin improve kidney function in people with chronic kidney disease |
|
Scientific Title of Study
|
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 Acronym |
|
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| 1378-0005, Version 3.0, dated 30 Mar 2022 |
Protocol Number |
| 2021-001434-19 |
EudraCT |
| NCT05182840 |
ClinicalTrials.gov |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Designation |
|
| Affiliation |
|
| Address |
|
| Phone |
|
| Fax |
|
| Email |
|
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Annappa Kamath |
| Designation |
Senior Solutions Consultant Director |
| Affiliation |
PAREXEL International Clinical Research Private Limited |
| Address |
CoWrks, Coworking Spaces Pvt. Ltd. – RMZ Eco World, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village
Bangalore Rural
KARNATAKA
560103
India |
| Phone |
918067169360 |
| Fax |
918067723001 |
| Email |
Annappa.Kamath@PAREXEL.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Annappa Kamath |
| Designation |
Senior Solutions Consultant Director |
| Affiliation |
PAREXEL International Clinical Research Private Limited |
| Address |
CoWrks, Coworking Spaces Pvt. Ltd. – RMZ Eco World, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village
KARNATAKA
560103
India |
| Phone |
918067169360 |
| Fax |
918067723001 |
| Email |
Annappa.Kamath@PAREXEL.com |
|
|
Source of Monetary or Material Support
|
| Boehringer Ingelheim International GmbH Binger Strasse 173 55216 Ingelheim am Rhein
Germany |
|
|
Primary Sponsor
|
| Name |
Boehringer Ingelheim International GmbH |
| Address |
Binger Strasse 173
55216 Ingelheim am Rhein
Germany
|
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| PAREXEL International Clinical Research Private Limited |
CoWrks, Coworking Spaces Pvt. Ltd. – RMZ Eco World, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village, BENGALURU – 560103, Karnataka, INDIA |
|
|
Countries of Recruitment
|
Argentina
Australia
Belgium
Brazil
Bulgaria
Canada
China
Czech Republic
Denmark
Finland
France
Germany
Greece
Hong Kong
Hungary
India
Israel
Italy
Japan
Malaysia
Mexico
Norway
Peru
Philippines
Poland
Portugal
Republic of Korea
Russian Federation
South Africa
Spain
Sweden
Switzerland
Turkey
Ukraine
United States of America
Viet Nam |
Sites of Study
Modification(s)
|
| No of Sites = 13 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Raj Kawar Yadav |
All India Institute of Medical Sciences |
Department of Nephrology, Room No 4087A, 4th Floor,
Teaching Block, Sri Aurobindo Marg, Ansari Nagar East, New Delhi - 110029
New Delhi
DELHI |
01126588500
01126588500
rkyadavnephrology@gmail.com |
| Dr Nihal Thomas |
Christian Medical College |
Department of Endocrinology, 810, Diabetes and Metabolism, Vellore - 632002
Vellore
TAMIL NADU |
9843111996
04162281000
nihal_thomas@yahoo.com |
| Dr Sinha Dhananjay Kumar |
Galaxy Lifecare Services Pvt Ltd |
Department of Nephrology, Plot no 427, Dayal Enclave, Mehmoorganj, Varanasi – 221010
Varanasi
UTTAR PRADESH |
9415304564
08874205817
dksinha15@gmail.com |
| Dr Gulati Yuvraj |
Ganesh Shankar Vidyarthi Memorial Medical College |
Department of Nephrology, GSVM medical college, Swaroop Nagar, Kanpur – 208002
Kanpur Nagar
UTTAR PRADESH |
7505873663
05122535881
yuvraj.gulati@gmail.com |
| Dr Meenakshi Bhattacharya |
Government Medical College and Hospital |
Department of Medicine, 2nd floor, Government Medical College and Hospital, Panchakki Road, Aurangabad – 431001
Aurangabad
MAHARASHTRA |
9922931527
02402402412
mabhattacharya@gmail.com |
| Dr Saxena Navneet |
Jaipur National University Institute for Medical Science & Research Centre |
Department of Nephrology, Dr Jaswant Goyal, Chief Advisor, Medical Sciences, Jagatpura, Jaipur - 302017
Jaipur
RAJASTHAN |
8696903400
18001021900
drnavneet.nephro@jnujaipur.ac.in |
| Dr Niranjan M R |
K R Hospital |
Department of Nephrology, Irwin Road, Mysuru-570001
Mysore
KARNATAKA |
9448672501
08212526200
drniranjanmr@gmail.com |
| Dr Khetan Prakash Prahlad |
Kingsway Hospitals |
Department of Nephrology, Room no 401, 4th Floor, 44, Kingsway Near Kasturchand Park, Nagpur - 440001
Nagpur
MAHARASHTRA |
9823071748
07126789100
prakashkhe@gmail.com |
| Dr Dinesh Khullar |
Max Super Specialty Hospital |
Department of Nephrology, 1-Press Enclave road, Saket - 110017
New Delhi
DELHI |
011-66114545
011-26510050
drdineshkhullar@gmail.com |
| Dr Umapati Hegde |
Muljibhai Patel Urological Hospital |
Department of
Nephrology, Dr. Virendra Desai road, Nadiad-387001
Kheda
GUJARAT |
02682520323
02682520248
umapatih@gmail.com |
| Dr Savalia Denish Dhirajlal |
Shree Giriraj Multispecialty Hospital |
Department of Nephrology, 27 Navjot Park Corner, 150 Feet Ring Road, Rajkot-360005
Rajkot
GUJARAT |
7730072741
02817151203
drsavalia@gmail.com |
| Dr Bal Ram Sharma |
SMS Medical College & Hospital |
Department of Endocrinology Room No. 43 A, Fourth Floor Dhanvantri OPD Block,
Jaipur -302004, Rajasthan, India
Jaipur
RAJASTHAN |
9660226666
drbalramendo@gmail.com |
| Dr Jain Siddharth Hariprasad |
Unity Hospital, Unity Trauma Center And ICU |
Department of Nephrology, D.R. World, Opp Raghuvir Business Empire, Aai Mata Rd, Parvat Patiya, Surat - 395010
Surat
GUJARAT |
9979530073
02616107000
drsiddharthhjain@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 13 |
| Name of Committee |
Approval Status |
| Ethics Committee GSVM Medical College, Kanpur |
Approved |
| Ethics Committee SMS Medical College & Attached Hospitals, Jaipur, Rajasthan |
Approved |
| Galaxy Hospital Ethics Committee, Galaxy Lifecare Services Private Limited, Uttar Pradesh |
Approved |
| IEC-Mysore Medical College and Research Institute and Associated Hospital, Mysore |
Approved |
| Institute Ethics Committee, All India Institute of Medical Sciences , New Delhi |
Approved |
| Institutional Ethics committee, Department of Pharmacology, Government Medical College, Aurangabad |
Approved |
| Institutional Ethics Committee, Jaipur National University Institute for Medical Sciences and Research Centre, Jaipur |
Approved |
| Institutional Review Board-Ethics Committee Silver, Christian Medical College, Vellore |
Approved |
| Kingsway Hospitals Ethics Committee, Nagpur |
Approved |
| Max Healthcare Ethics Committee Ground Floor, Office of Ethics Committee West Block, New Delhi |
Approved |
| Muljibhai Patel Society for Research in Nephro- Urology Ethics Committee, Gujarat |
Approved |
| Shree Giriraj Hospital Research Ethics Committee, Shree Giriraj Multispeciality Hospital, Gujarat |
Approved |
| Unity Hospital Ethics Committee, Unity Hospital, Gujarat |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: N189||Chronic kidney disease, unspecified, (2) ICD-10 Condition: E132||Other specified diabetes mellituswith kidney complications, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
BI 690517 and Empagliflozin |
3 mg, 10 mg and 20 mg of BI 690517 and Empagliflozin 10 mg
film-coated tablets will be given
orally once daily and duration of
treatment will be 22 weeks (8 weeks run-in with empagliflozin/placebo and 14 weeks of treatment with BI 690517/placebo alone or in combination with
empagliflozin/ placebo)
|
| Comparator Agent |
Placebo to BI 690517 and
Placebo to Empagliflozin
|
Placebo matching each dose of BI 690517 and empagliflozin |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1) Signed and dated written informed consent in accordance with International Council on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
2) Male or female patients of legal adult age (according to local legislation) and aged greater than or equal to 18 years at time of consent
3) estimated Glomerular Filtration Rate (eGFR, Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) greater than or equal to 30 and less than 90 mL/min/1.73 m2 at Visit 1 by central laboratory analysis
4) Urine Albumin Creatinine Ratio (UACR) greater than or equal to 200 and less than 5,000 mg/g in spot urine (midstream urine sample) by central laboratory analysis at Visit 1.1
5) If the patient is taking any of the following medications they should be on a stable dose for at least 4 weeks prior to visit 1 and until first randomisation prior to run-in with no planned change of the therapy during the trial: anti-hypertensives, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), endothelin receptor antagonists, low dose systemic steroids (e.g. prednisolone less than or equal to 10 mg or equivalent)
6) Treatment with a clinically appropriate, stable dose of either Angiotensin-Converting Enzyme Inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) (but not both together), for greater than or equal to 4 weeks prior to visit 1 and until first randomisation with no planned change of the therapy during the trial
7) In the Investigators opinion, any kind of diagnosed chronic kidney disease (Diagnosis can be reached by standard clinical method, no biopsy required). Patients with diabetic kidney disease must have type 2 diabetes mellitus and their treatment (including GLP1 receptor agonist) should be unchanged or changes deemed minor (according to investigators judgement) within 4 weeks prior to Visit 1 and until first randomisation
8) Glycated Haemoglobin (HbA1c) less than 10.0% at Visit 1 measured by the central laboratory
9) Serum potassium less than or equal to 4.8 mmol/L at Visit 1 measured by the central laboratory
10) Seated Systolic Blood Pressure (SBP) greater than or equal to 110 and less than or equal to 160 mmHg and Diastolic Blood Pressure (DBP) greater than or equal to 65 and less than or equal to 110 mmHg at Visit 1 (mean values from three Blood Pressure (BP) measurements) and optimised anti-hypertensive treatment according to local standard of care and investigators judgement
11) Body Mass Index (BMI) greater than or equal to 18.5 and less than 50 kg/m2 at Visit 1
12) Women of child-bearing potential2 (WOCBP) must be ready and able to use highly effective methods of birth control. Such methods should be used throughout the trial. Men must be vasectomised or willing and able to use a condom if their partner is a WOCBP
Additional inclusion criteria to be assessed before second randomisation (start of Treatment Period):
13) Serum potassium less than or equal to 4.8 mmol/L measured by local or central laboratory within 7 days prior to randomisation to the Treatment Period
14) eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) greater than or equal to 20 mL/min/1.73 m2 measured by local or central laboratory within 7 days prior to randomisation to the Treatment Period |
|
| ExclusionCriteria |
| Details |
1) Treatment with inhibitors of aldosterone mediated effects (e.g., mineralocorticoid receptor antagonists such as spironolactone), or intake of other potassium sparing diuretics (e.g., amiloride) within 7 days prior to first randomisation or planned during trial treatment phase
2) Treatment with other Renin Angiotensin Aldosterone System (RAAS) interventions (apart from either Angiotensin-Converting Enzyme Inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB)) within 4 weeks prior to Visit 1 and throughout screening or planned during the trial. Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial are also excluded
3) Type 1 diabetes mellitus, or history of other autoimmune causes of diabetes mellitus (e.g. Latent Autoimmune Diabetes (LADA))
4) Patients at increased risk of ketoacidosis in the opinion of the investigator
5) Currently receiving Sodium-glucose cotransporter (SGLT)-2 or SGLT-1/2 inhibitor or planned initiation during the trial |
|
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Method of Generating Random Sequence
|
Stratified randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Change from treatment period baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in First Morning Void urine |
up to 14 weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline |
up to 14 weeks |
| UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline |
up to 14 weeks |
|
|
Target Sample Size
|
Total Sample Size="552"
Sample Size from India="38"
Final Enrollment numbers achieved (Total)= "38"
Final Enrollment numbers achieved (India)="18" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
19/04/2022 |
| Date of Study Completion (India) |
27/06/2023 |
| Date of First Enrollment (Global) |
02/02/2022 |
| Date of Study Completion (Global) |
10/07/2023 |
|
Estimated Duration of Trial
|
Years="2"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
This study is open to adults with chronic kidney
disease. People with and without type 2 diabetes can take part in this studyThe purpose of this study is to find out
whether a medicine called BI 690517 improves kidney function in people with
chronic kidney disease when taken alone or in combination with a medicine
called empagliflozin.
In the first part of the study,
participants take empagliflozin or placebo as tablets every day for 2 months.
Placebo tablets look like empagliflozin tablets but do not contain any
medicine.
In the second part, participants are
divided into several groups. Depending on the group, the participants then
additionally take different doses of BI 690517 or placebo as tablets for 3.5
months. In this case, placebo tablets look like BI 690517 tablets but do not
contain any medicine.
Participants are in the study for about 6
months. During this time, they visit the study site about 12 times. Where
possible, about 4 of the 12 visits can be done at the participant’s home
instead of the study site. The trial staff may also contact the participants by
phone or video call.
Participants collect urine
samples at home. These samples are then analysed to assess kidney function. At
the end of the trial the results are compared between the different groups. The
doctors also regularly check participants health and take note of any unwanted
effects. |