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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03842761
• Other study ID #: 1366-0020
• Status: Completed
• Phase: Phase 1
• Start date: March 6, 2019
• Est. completion date: May 20, 2021

Study information

• Verified date: June 2021
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: May 20, 2021
• Est. primary completion date: April 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Healthy
• Hepatic Insufficiency
• Liver Failure

Intervention

Drug:
• BI 685509
Tablet
• Placebo
Tablet

Locations

Country	Name	City	State
United States	American Research Corporation at the Texas Liver Institute	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The percentage of subjects with drug-related Adverse Events (AEs) among different dose regimes over each up-titration		Up to day 28
Secondary	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
Secondary	Cmax (maximum measured concentration of the analyte in plasma)		Up to 72 hours
Secondary	AUCt,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t) [AUCt,ss will be AUC0-12,ss for bid dosing]		Up to 72 hours
Secondary	Cmax,ss (maximum measured concentration of the analyte in plasma at steady)		Up to 72 hours
Secondary	Change from baseline in seated systolic blood pressure (SBP)		Baseline and Up to 28 days
Secondary	Change from baseline in seated diastolic blood pressure (DBP)		Baseline and Up to 28 days
Secondary	Change from baseline in heart rate (HR)		Baseline and Up to 28 days
Secondary	Change from baseline in body weight		Baseline and Up to 28 days

External Links

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