Randomised, Double-blind, Placebo-controlled Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 3 Multiple Rising Oral Doses of BI 685509 Over 28 Days in Male and Female Patients With Diabetic Nephropathy

Boehringer Ingelheim35 sites in 5 countries75 target enrollmentOctober 17, 2017

ConditionsDiabetic Nephropathies

InterventionsBI 685509 Placebo

DrugsBI 685509 Placebo

Overview

Phase: Phase 1
Intervention: BI 685509
Conditions: Diabetic Nephropathies
Sponsor: Boehringer Ingelheim
Enrollment: 75
Locations: 35
Primary Endpoint: Percentage of patients with drug related Adverse Events (AEs)
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The main objective of this trial is the safety and tolerability of 3 multiple rising oral doses of BI 685509 over 28 days in male and female patients with Diabetic Nephropathy (DN) as adjunctive to Angiotensin Converting Enzyme inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB). Another objective is the change in Urine Albumin Creatinine Ratio (UACR), an important diagnostic marker of nephropathy.

Registry

clinicaltrials.gov

Start Date

October 17, 2017

End Date

December 10, 2019

Last Updated

6 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
•Male or postmenopausal (last menstruation ≥ 2 years ago) patients, or female patients who are sterilized by either hysterectomy, bilateral salpingectomy and/or bilateral oophorectomy. Male patients with partners of child-bearing potential must be willing to use condoms from the time of the first intake of study drug until follow-up.
•eGFR (Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula) ≥ 20 and \< 75 ml/min/1.73 m2 at Visit 1 measured by the central laboratory and no planned start of renal replacement therapy during the trial
•UACR ≥ 200 and \<3500 mg/g in spot urine (midstream urine sample) at Visit 1 measured by the central laboratory
•Treatment with either ACEi or ARB, stable dose since ≥ 4 weeks before Visit 1 with no planned change of the therapy
•Patients with type 1 or type 2 diabetes mellitus, diagnosed before informed consent and treated with insulin, glucagon-like peptide (GLP) 1 agonists and/or oral antidiabetic medication. Treatment should have been unchanged (investigator's judgment) within 4 weeks before Visit 1 and until randomisation
•Glycated Haemoglobin (HbA1c) \< 10.0% at Visit 1 measured by the central laboratory
•Seated Systolic Blood Pressure (SBP) ≥ 110 and ≤ 180 mmHg and Diastolic Blood Pressure (DBP) ≥ 70 and ≤ 110 mmHg at Visit 1
•Age at screening ≥ 18 years for male and permanently sterilized female patients and ≥ 45 years for postmenopausal female patients
•Body Mass Index (BMI) ≥ 18.5 and \< 45 kg/m2

Exclusion Criteria

•Treatment with SGLT2 inhibitors and/or phosphodiesterase inhibitors, nitrates or riociguat, from screening (Visit 1) or within 5 half-lives before randomisation whatever is earlier.
•Any laboratory value more than 3 times above upper limit of normal (ULN) at screening (Visit 1) or any other laboratory value outside the reference range and clinically relevant (for safe participation) in the investigator judgment
•Confirmed non-diabetic renal disease in the opinion of investigator
•Any other medical condition that in the investigator's opinion poses a safety risk for the patient or may interfere with the study objectives including
•symptomatic heart failure (NYHA III/IV),
•known history of tachycardia and/or atrial fibrillation
•clinically relevant arrhythmias
•coronary heart disease not compensated by medical treatment (supine pulse rate \>70 beats per minute, existing angina pectoris)
•\<6 months after myocardial infarction.
•Medical history of cancer or treatment for cancer in the last two years prior to Visit 1 (except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix, and prostatic cancer of low grade \[T1 or T2\] is exempted)

Arms & Interventions

BI 685509 Dose 1

Intervention: BI 685509

BI 685509 Dose 2

Intervention: BI 685509

BI 685509 Dose 3

Intervention: BI 685509

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Percentage of patients with drug related Adverse Events (AEs)

Time Frame: Up to 35 days

Secondary Outcomes

Change from baseline in log transformed Urine albumin creatinine ratio (UACR) measured in morning void urine(Up to 28 days)
Change from baseline in log transformed Urine albumin creatinine ratio (UACR) measured in 10-hour urine(Up to 28 days)