Safety and Efficacy of Different Oral Doses of BAY94-8862 in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Nephropathy

Phase 2

Completed

• Conditions: Diabetic Nephropathies
• Interventions: Drug: Finerenone (BAY94-8862); Drug: Placebo

• Registration Number: NCT01874431
• Lead Sponsor: Bayer

Brief Summary

To assess a new drug, BAY94-8862 given orally at different doses, to evaluate whether it was safe and can help the well being of patients with type 2 diabetes and diabetic nephropathy. These treatment doses were compared to placebo.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-06-07
• Study First Submitted QC: 2013-06-07
• Study First Posted: 2013-06-11
• Study Start: 2013-06-12
• Primary Completion: 2014-07-09
• Study Completion: 2014-08-07
• Disposition First Submitted: 2015-06-04
• Disposition First Submitted QC: 2015-06-04
• Disposition First Posted: 2015-07-01
• Results First Submitted: 2021-04-15
• Results First Submitted QC: 2021-04-15
• Results First Posted: 2021-05-04
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-30
• Last Update Posted: 2021-07-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 823

Inclusion Criteria

• Men and women aged 18 years and older.The lower age limit may be higher if legally required in the participating country

• Women of childbearing potential can only be included in the study if a pregnancy test is negative and if they agree to use adequate contraception when sexually active.

• Subjects with type 2 diabetes mellitus fulfilling at least 1 of the following criteria

  • are on oral antidiabetics and / or insulin,
  • have a documented fasting glucose >/= 7.0 mmol/L in the medical history,
  • have a 2 hour plasma glucose >/=11.1 mmol/L during an oral glucose tolerance test in the medical history, or
  • have a glycated hemoglobin (HbA1c) >/=6.5% [National Glycohemoglobin Standardization Program (NGSP) / Diabetes Control and Complications Trial (DCCT)] in the medical history or at the run-in visit

• Subjects with a clinical diagnosis of diabetic nephropathy (DN) based on at least 1 of the following criteria:

  • Persistent very high albuminuria defined as urinary albumin-to-creatine ratio (UACR) of >/=300 mg/g ( >/= 34 mg/mmol) in 2 out of 3 first morning void samples and estimated glomerular filtration rate (eGFR) >/=30 mL/min/1.73 m² but < 90 mL/min/1.73m² (Chronic Kidney Disease Epidemiology Collaboration, CKD EPI) (mL = milliliter; min = minute; m2 = square meter; g = gram; mmol = millimole) or
  • Persistent high albuminuria defined as UACR of >/=30 mg/g but <300 mg/g in (>/=3.4mg/mmol but <34 mg/mmol) in 2 out of 3 first morning void samples and eGFR >/=30 mL/min/1.73 m² but < 90 mL/min/1.73m²

• Subjects treated with an angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) for at least 3 months without any adjustments to this therapy for at least 4 weeks prior to the screening visit

• Serum potassium </= 4.8 mmol/L at both the run-in visit and the screening visit

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Exclusion Criteria

• Non-diabetic renal disease
• Glycated hemoglobin (HbA1c) >12% at the run-in visit or the screening visit
• UACR >3000 mg/g (339mg/mmol) in any of the urinary first morning void samples at the run-in visit or screening visit
• Hypertension with mean sitting systolic blood pressure (SBP) >/=180 mmHg or mean sitting diastolic blood pressure (DBP) >/=110 mmHg at the run-in visit or mean supine SBP >/=160 mmHg or mean sitting DBP >/=100 mmHg at the screening visit
• Subjects with a clinical diagnosis of heart failure with reduced ejection fraction (HFrEF) and persistent symptoms (New York Heart Association class II-IV) at the run-in visit
• Concomitant therapy with eplerenone, spironolactone, any renin inhibitor, or potassium-sparing diuretic
• Dialysis for acute renal failure within the previous 6 months prior to the run-in visit

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Finerenone (BAY94-8862) (15 mg)	Finerenone (BAY94-8862)	15 mg dose oral once daily for 90 days
Finerenone (BAY94-8862)(20 mg)	Finerenone (BAY94-8862)	20 mg dose oral once daily for 90 days
Placebo	Placebo	Placebo oral dose once daily for 90 days
Finerenone (BAY94-8862) (1.25 mg)	Finerenone (BAY94-8862)	1.25 mg dose oral once daily for 90 days
Finerenone (BAY94-8862)(2.5 mg)	Finerenone (BAY94-8862)	2.5 mg dose oral once daily for 90 days
Finerenone (BAY94-8862)(5 mg)	Finerenone (BAY94-8862)	5 mg dose oral once daily for 90 days
Finerenone (BAY94-8862)(7.5 mg)	Finerenone (BAY94-8862)	7.5 mg dose oral once daily for 90 days
Finerenone (BAY94-8862) (10 mg)	Finerenone (BAY94-8862)	10 mg dose oral once daily for 90 days

Primary Outcome Measures

Name	Time	Method
Ratio of UACR at Day 90 to UACR at Baseline	Baseline and Day 90±2	Albumin-to-creatinine ratio (UACR) is defined as gram of albumin per kilogram of creatinine. UACR was calculating the average of 3 first morning void samples taken on 3 consecutive days.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Day 90 in Serum Potassium	Baseline and Day 90±2
Change From Baseline to Day 90 in eGFR	Baseline and Day 90±2	An estimated glomerular filtration rate (eGFR) indicates the renal function. An eGFR was calculated based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
Change From Baseline to Day 90 in KDQOL-36 Domain Score (Effects of Kidney Disease)	Baseline and Day 90±2	The Kidney Disease QOL \[KDQOL\]-36 questionnaire is a specific measure of Health-Related Quality of Life (HRQoL) for chronic kidney disease (CKD) that includes effects and burden of kidney disease as well as physical and mental health scores. Index score ranges from 0 (severe problems in all items) to 100 (no problem in all items). "Effects of Kidney disease" subscore was analyzed.
Change From Baseline to Day 90 in EQ-5D Scores (EQ5D - Visual Analog Scale)	Baseline and Day 90±2	EuroQol Group 5-Dimension, 3-Level (EQ-5D-3L) questionnaires consist of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. EQ VAS was analyzed for this endpoint and it ranges from 0 (worst possible health state) to 100 (best possible health state).