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

NCT03842761 | Completed Phase 1 FDA Drug

• 1 other identifier: 1366-0020
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy; Hepatic Insufficiency

Outcome Measures

Primary Outcomes (1)

• The percentage of subjects with drug-related Adverse Events (AEs) among different dose regimes over each up-titration

  Up to day 28

Secondary Outcomes (8)

• 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

• Cmax (maximum measured concentration of the analyte in plasma)

  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

Study Arms (4)

Dose group 1

EXPERIMENTAL

Low Dose

Drug: BI 685509; Drug: Placebo

Dose group 2

EXPERIMENTAL

Medium Dose

Drug: BI 685509; Drug: Placebo

Dose group 3

EXPERIMENTAL

High Dose

Drug: BI 685509; Drug: Placebo

Dose Group 4

EXPERIMENTAL

Dose for healthy volunteers dependent on results from prior dose groups with patients

Drug: BI 685509; Drug: Placebo

Interventions

BI 685509 DRUG

Tablet

Dose Group 4; Dose group 1; Dose group 2; Dose group 3

Placebo DRUG

Tablet

Dose Group 4; Dose group 1; Dose group 2; Dose group 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)
• 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
• 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
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

American Research Corporation at the Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Hepatic Insufficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: February 15, 2019
• Study Start: March 6, 2019
• Primary Completion: April 9, 2021
• Study Completion: May 20, 2021
• Last Updated: June 10, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)