A Study to Test How Different Doses of BI 685509 Are Tolerated in Patients With Liver Problems

Randomized, Double-blind, Placebo-controlled Trial to Investigate Safety, Tolerability, and Pharmacokinetics of Multiple Rising Oral Doses of BI 685509 Over 28 Days in Patients With Mild and Moderate Hepatic Impairment and of Single Oral BI 685509 Dose Compared to Healthy Volunteers

The primary objective of this trial is the evaluation of safety and tolerability in patients with mild to moderate hepatic impairment [Child-Turcotte-Pugh (CTP) classification A and B] over different dose regimes of BI 685509 compared to placebo. A secondary objective is to investigate pharmacokinetics of different doses of BI 685509 in patients with mild to moderate hepatic impairment (CTP A and CTP B). In addition, another secondary objective is to compare safety, tolerability, and pharmacokinetics in patients with mild to moderate hepatic impairment (CTP A and CTP B) of single BI 685509 dose to individually matched healthy volunteers

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency; Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 685509

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at the Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria for all trial participants:

• Age ≥ 18 years at Screening
• Male or female. Women of childbearing potential (WOCBP) participants and male participants able to father a child must be ready and able to use a highly effective method of birth control per ICH M3 (R2) that results in a low failure rate of less than 1% per year when used consistently and correctly throughout the Trial
• Mean Arterial Pressure (MAP) ≥ 85 mmHg at screening visit
• Estimated Glomerular Filtration rate (eGFR) > 70 mL/min/1.73m² according to the CKD-EPI formula at screening visit
• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial

Key inclusion for Patient Groups 1 and 2

• If on treatment with non-selective beta blockers (NSBB), stable dose since ≥ 8 weeks prior to screening, with no planned dose change of the therapy during study conduct. All other medications stable 4 weeks prior to screening.
• Patient Group 1: Patients with CTP A and portal hypertension (defined as liver stiffness >15 kPa during screening) and without a previous decompensation event [ascites, variceal hemorrhage, encephalopathy, or jaundice (except Gilbert's disease or hemolysis when bilirubin will be almost exclusively indirect hyperbilirubinemia)]. Self-limited and resolved historical events of decompensation like ascites or encephalopathy are allowed if they have occurred at least 6 weeks prior to screening and do not require continued therapeutic intervention at the time of screening.
• Patient Group 2: Patients with CTP B (with liver stiffness >15 kPa during screening)

Key inclusion for Healthy Volunteer group

• Subjects who are healthy, according to the investigator's assessment, individually matched to a participant among Patient Groups 1 and 2 according to the following criteria: age within ± 5 years, body weight within ± 15%, and gender
• Further inclusion criteria apply

Key exclusion for all trial participants

• Ongoing chronic alcohol or drug use, which in the investigator's opinion, makes the patient an unreliable trial participant or unlikely to complete the trial.
• History of relevant orthostatic hypotension, fainting spells, or blackouts based on the investigator´s judgment

Key exclusion for Patient Groups

• Patient Group 2: treatment-refractory ascites
• Patient Group 2: recent decompensation event (refractory ascites, recurrent variceal hemorrhage, recurrent hepatic encephalopathy, spontaneous bacterial peritonitis or hepatorenal syndrome) within 6 weeks of screening
• Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dose group 1; Low Dose	Drug: Placebo; Tablet; Drug: BI 685509; Tablet
EXPERIMENTAL: Dose group 2; Medium Dose	Drug: Placebo; Tablet; Drug: BI 685509; Tablet
EXPERIMENTAL: Dose group 3; High Dose	Drug: Placebo; Tablet; Drug: BI 685509; Tablet
EXPERIMENTAL: Dose Group 4; Dose for healthy volunteers dependent on results from prior dose groups with patients	Drug: Placebo; Tablet; Drug: BI 685509; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of subjects with drug-related Adverse Events (AEs) among different dose regimes over each up-titration	Up to day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax (maximum measured concentration of the analyte in plasma)	Up to 72 hours
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to time of the last quantifiable data point)	Baseline and Up to 72 hours
AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) [AUCτ,ss will be AUC0-12,ss for bid dosing]	Up to 72 hours
Cmax,ss (maximum measured concentration of the analyte in plasma at steady)	Up to 72 hours
Change from baseline in seated systolic blood pressure (SBP)	Baseline and Up to 28 days
Change from baseline in seated diastolic blood pressure (DBP)	Baseline and Up to 28 days
Change from baseline in heart rate (HR)	Baseline and Up to 28 days
Change from baseline in body weight	Baseline and Up to 28 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 6, 2019
• Primary Completion (ACTUAL): April 9, 2021
• Study Completion (ACTUAL): May 20, 2021

Study Registration Dates

• First Submitted: February 13, 2019
• First Submitted That Met QC Criteria: February 14, 2019
• First Posted (ACTUAL): February 15, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 10, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency
• Other Study ID Numbers: 1366-0020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datasharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No