HealthyPhase 1NCT03842761
A Study to Test How Different Doses of BI 685509 Are Tolerated in Patients With Liver Problems
A Phase 1 study testing BI 685509 in people with Healthy and Hepatic Insufficiency, run by Boehringer Ingelheim at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Healthy, Hepatic Insufficiency
- What is being tested?
- BI 685509
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Mar 2019to 20 May 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- Further inclusion criteria apply
Who cannot join
- 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
- Further exclusion criteria apply
Trial locations and contacts
1 site in 1 country.
United States1 site
American Research Corporation at the Texas Liver Institute
San Antonio, Texas, 78215
About this study
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
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
- Being tested
- BI 685509, Placebo
- Medical subject headings
- Hepatic Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 685509Drug
Tablet
PlaceboDrug
Tablet
| Study group | Role | What they receive |
|---|---|---|
| Dose group 1 | Experimental | Low Dose Receives: Drug: BI 685509; Drug: Placebo |
| Dose group 2 | Experimental | Medium Dose Receives: Drug: BI 685509; Drug: Placebo |
| Dose group 3 | Experimental | High Dose Receives: Drug: BI 685509; Drug: Placebo |
| Dose Group 4 | Experimental | Dose for healthy volunteers dependent on results from prior dose groups with patients Receives: Drug: BI 685509; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The percentage of subjects with drug-related Adverse Events (AEs) among different dose regimes over each up-titration
Measured: 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)
Measured: Baseline and Up to 72 hours
Cmax (maximum measured concentration of the analyte in plasma)
Measured: 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]
Measured: Up to 72 hours
Cmax,ss (maximum measured concentration of the analyte in plasma at steady)
Measured: Up to 72 hours
Change from baseline in seated systolic blood pressure (SBP)
Measured: Baseline and Up to 28 days
Change from baseline in seated diastolic blood pressure (DBP)
Measured: Baseline and Up to 28 days
Change from baseline in heart rate (HR)
Measured: Baseline and Up to 28 days
Change from baseline in body weight
Measured: Baseline and Up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start6 Mar 2019
- Primary completion9 Apr 2021
- Study completion20 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03842761
- Sponsor's protocol ID
- 1366-0020
- Status last verified
- Jun 2021
- First submitted
- 13 Feb 2019
- Last updated
- 10 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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
Publications
Lawitz EJ, Ertle J, Schoelch C, Gashaw I, McRae MP, Helmke SM, Everson GT. Hepatic improvement within 27 days of avenciguat treatment in Child-Pugh A cirrhosis detected by an oral cholate challenge test. Liver Transpl. 2024 Oct 1;30(10):982-990. doi: 10.1097/LVT.0000000000000420. Epub 2024 Jun 12.
PubMed 38869987
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03842761
- Acronym / sponsor ID
- 1366-0020
- Conditions
- Healthy, Hepatic Insufficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 6 Mar 2019 (actual)
- Primary completion
- 9 Apr 2021 (actual)
- Study completion
- 20 May 2021 (actual)
- First posted
- 15 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose group 1 | Experimental | Drug: BI 685509, Drug: PlaceboLow Dose |
| Dose group 2 | Experimental | Drug: BI 685509, Drug: PlaceboMedium Dose |
| Dose group 3 | Experimental | Drug: BI 685509, Drug: PlaceboHigh Dose |
| Dose Group 4 | Experimental | Drug: BI 685509, Drug: PlaceboDose for healthy volunteers dependent on results from prior dose groups with patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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 exclusion criteria (5 listed)
- 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
- Further exclusion criteria apply
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BI 685509Tablet | Drug | Dose Group 4, Dose group 1, Dose group 2, Dose group 3 |
| PlaceboTablet | Drug | Dose Group 4, Dose group 1, Dose group 2, Dose group 3 |
Primary outcome
The percentage of subjects with drug-related Adverse Events (AEs) among different dose regimes over each up-titration
Time frame: Up to day 28
8 secondary outcomes
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)
Time frame: Baseline and Up to 72 hours
Cmax (maximum measured concentration of the analyte in plasma)
Time frame: 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]
Time frame: Up to 72 hours
Cmax,ss (maximum measured concentration of the analyte in plasma at steady)
Time frame: Up to 72 hours
Change from baseline in seated systolic blood pressure (SBP)
Time frame: Baseline and Up to 28 days
Change from baseline in seated diastolic blood pressure (DBP)
Time frame: Baseline and Up to 28 days
Change from baseline in heart rate (HR)
Time frame: Baseline and Up to 28 days
Change from baseline in body weight
Time frame: Baseline and Up to 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2021.
- Derived from this study: PubMed 38869987Lawitz EJ, Ertle J, Schoelch C, Gashaw I, McRae MP, Helmke SM, Everson GT. Hepatic improvement within 27 days of avenciguat treatment in Child-Pugh A cirrhosis detected by an oral cholate challenge test. Liver Transpl. 2024 Oct 1;30(10):982-990. doi: 10.1097/LVT.0000000000000420. Epub 2024 Jun 12.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BI 685509 in people with Healthy and Hepatic Insufficiency, run by Boehringer Ingelheim at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The percentage of subjects with drug-related Adverse Events (AEs) among different dose regimes over each up-titration (time frame: Up to day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03842761, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2021.