CADA DIA: A Double-blind Study to Investigate Efficacy, Safety and Tolerability of BAY1142524 in Patients With Type II Diabetes and a Clinical Diagnosis of Diabetic Kidney Disease

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT03412006

Collaborator

(none)

152

Enrollment

Locations

Arms

20.2

Actual Duration (Months)

5.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the trial is the analysis of safety and efficacy of the chymase inhibitor BAY1142524 at a dose of 25 mg BID in comparison to placebo using a 6 months treatment period in type II diabetic patients with a clinical diagnosis of diabetic kidney disease. BAY1142524 or placebo will be given on top of evidence-based standard of care for diabetic kidney disease. Primary objective is the analysis of first signs of efficacy as determined by favourable changes in urinary albumin creatinine ratio. Secondary objective is the analysis of safety and tolerability as evidenced by the incidence and severity of adverse events. 64 valid patients have to complete treatment with verum and 32 valid patients have to complete treatment with placebo.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Kidney Disease	Drug: Fulacimstat (BAY1142524) Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

152 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Multicenter Study to Assess the Efficacy and Safety of a 6 Month Oral Treatment With the Chymase Inhibitor BAY 1142524 at a Dose of 25 mg BID in Comparison to Placebo on Top of Standard of Care in Patients With Type II Diabetes and a Clinical Diagnosis of Diabetic Kidney Disease

Actual Study Start Date :

Feb 2, 2018

Actual Primary Completion Date :

Oct 2, 2019

Actual Study Completion Date :

Oct 10, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fulacimstat (BAY1142524) Patients have to have a clinical diagnosis of diabetic kidney disease and have to be treated with standard of care for this condition	Drug: Fulacimstat (BAY1142524) 25 mg BAY1142524 are given twice daily over a treatment period of 6 months
Placebo Comparator: Placebo Patients have to have a clinical diagnosis of diabetic kidney disease and have to be treated with standard of care for this condition	Drug: Placebo Matching placebo tablets are given twice daily over a treatment period of 6 months

Arm

Intervention/Treatment

Experimental: Fulacimstat (BAY1142524)

Patients have to have a clinical diagnosis of diabetic kidney disease and have to be treated with standard of care for this condition

Drug: Fulacimstat (BAY1142524)

25 mg BAY1142524 are given twice daily over a treatment period of 6 months

Placebo Comparator: Placebo

Patients have to have a clinical diagnosis of diabetic kidney disease and have to be treated with standard of care for this condition

Drug: Placebo

Matching placebo tablets are given twice daily over a treatment period of 6 months

Outcome Measures

Primary Outcome Measures

Change in urinary albumin to creatinine ratio (UACR) [Baseline and at 6 months]
The ratio of albumin to creatinin will be determined in first morning void urine at baseline (before treatment start) and after 6 months of treatment

Secondary Outcome Measures

Number of patients with treatment-emergent adverse event [From first intake of study drug up to 3 days after last administration of study drug]
Number of patients with serious adverse events [From first intake of study drug up to 3 days after last administration of study drug]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with Type 2 Diabetes Mellitus and a clinical diagnosis of diabetic kidney disease (DKD) (as judged by the investigator) who have finished their up-titration with an angiotensin receptor blocker (ARB) or an ACEI (angiotensin-converting enzyme inhibitor) to their maximum tolerated dose at least 3 months prior to the screening visit, whereby the maximum tolerated dose has to be at least as high as the minimal recommended dose of an ARB or ACEI according to local and/or international guidelines. Patients have to be treated with an ARB or ACEI, but not with both simultaneously, without any adjustments to this therapy for at least 4 weeks prior to the screening visit.
UACR >50 mg/g and <3000 mg/g in 2 out of 3 consecutive morning void samples at the screening and the baseline visit
estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 and <90 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at the screening visit and the baseline visit

Exclusion Criteria:

Non-DKD if it is the main diagnosis contributory to chronic kidney disease (CKD), as judged by the investigator
Known bilateral clinical relevant renal artery stenosis (>75%)
New York Heart Association (NYHA) Class IV
Acute kidney injury or dialysis within the last 3 months before the screening visit
Renal replacement therapy during study conduct
Renal allograft in place or a scheduled kidney transplant during study conduct
Stroke, transient ischemic cerebral attack, acute coronary syndrome, or hospitalization for heart failure in the last 3 months prior to screening visit
Clinically relevant hepatic dysfunction
Uncontrolled hypertension as evidenced by systolic blood pressure >160 mmHg, diastolic blood pressure >100 mmHg (mean of triplicate values at the screening or baseline visit)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Med Centre Diamedical 2013	Dimitrovgrad		Bulgaria	6400
2	MCOMH Preventsia-2000	Stara Zagora		Bulgaria	6000
3	Med. Center Equita	Varna		Bulgaria	9000
4	Steno Diabetes Center Copenhagen	Gentofte		Denmark	2730
5	Nordsjællands Hospital	Hillerød		Denmark	3400
6	Rigshospitalet	København		Denmark	2100
7	Pihlajalinna ITE Kuopio	Kuopio		Finland	70100
8	Terveystalo Oulu	Oulu		Finland	FI-90100
9	TAYS TKI Keskus Tutkimusvastaanotto	Tampere		Finland	33520
10	Turun yliopistollinen keskussairaala, kantasairaala	Turku		Finland	FIN-20520
11	Barzilai Medical Center	Ashkelon		Israel	7830604
12	Edith Wolfson Medical Center	Holon		Israel	5822012
13	Hadassah Hebrew University Hospital Ein Kerem	Jerusalem		Israel	9112001
14	The Nazareth Trust Hospital EMMS	Nazareth		Israel	16100
15	DMC - Diabetes Medical Center	Tel Aviv		Israel	6937947
16	Shamir Medical Center (Assaf Harofeh)	Zerifin		Israel	7030000
17	A.O.U. Policlinico Federico II Napoli	Napoli	Campania	Italy	80131
18	Univ. Alma Mater - Dip. Medicina Spec, Diagnostica e Sperim	Bologna	Emilia-Romagna	Italy	40138
19	IRCCS Casa Sollievo della Sofferenza	Foggia	Puglia	Italy	71013
20	A.O.U. di Padova	Padova	Veneto	Italy	35128
21	Complexo Hospitalario Universitario de Ferrol	Ferrol	A Coruña	Spain	15405
22	Hospital de Galdakao	Galdakao	Vizcaya	Spain	48960
23	Hospital Fundació Puigvert	Barcelona		Spain	08025
24	Centralsjukhuset Kristianstad	Kristianstad		Sweden	29185
25	Akardo MedSite AB	Stockholm		Sweden	114 46
26	S3 Clinical Research Centers	Vällingby		Sweden	162 68
27	Universitetssjukhuset Örebro	Örebro		Sweden	701 85