Hepatic ImpairmentPhase 1NCT04252495
The Effect of Hepatic Impairment on Aprocitentan Pharmacokinetics
A Phase 1 study testing Aprocitentan in people with Hepatic Impairment and Healthy Subjects, run by Idorsia Pharmaceuticals Ltd. at 2 sites in 2 countries.
Trial summary
This is a prospective, open-label, single-dose, Phase 1 study, to assess the effect of moderate hepatic impairment due to liver cirrhosis on the pharmacokinetics of aprocitentan (ACT-132577). Read more about this study
- Who is it for?
- Ages 30 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment, Healthy Subjects
- What is being tested?
- Aprocitentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 26 Jun 2020to 6 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 30 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Signed informed consent in a language understandable to the subject prior to any study-mandated procedure.
- Women of childbearing potential (WoCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1 and must agree to use highly effective methods of contraception from screening up to 30 days after study treatment.
- A Women of non-childbearing potential (WoNCBP) must meet one of the following criteria:
- Previous bilateral salpingectomy, salpingo-oophorectomy or hysterectomy.
- Premature ovarian failure confirmed by a specialist gynecologist.
- Post-menopausal, defined as 12 consecutive months with amenorrhea prior to screening without alternative medical cause and confirmed with a follicle stimulating hormone test.
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- Body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening.
- Normal renal function confirmed by a creatinine clearance at screening according to Cockcroft and Gault adjusted to age.
- Additional principal inclusion criteria for subjects with moderate hepatic impairment (Group 1)
- Moderate hepatic function impairment due to liver cirrhosis defined as a score of 7-9 (inclusive) according to the Child-Pugh classification.
- Systolic blood pressure 95 to 160 mmHg, diastolic blood pressure 60 to 95 mmHg, and pulse rate 50 to 100 bpm (inclusive), measured on the same arm, after 5 minutes in the supine position at screening and on Day 1 pre-dose.
- International normalized ratio equal or less than 2.5 at screening.
- Stable concomitant medications for at least 3 weeks prior to screening and up to Day 1 and expected to be stable during the conduct of the study.
- Additional principal inclusion criteria for healthy subjects (Group 2)
- Healthy on the basis of medical history, physical examination, cardiovascular assessments, and clinical laboratory tests.
Who cannot join
- Pregnant or lactating women.
- Previous exposure to aprocitentan and/or macitentan.
- Known hypersensitivity to any excipients of the drug formulation.
- Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
- Any signs or symptoms of active, ongoing infection judged to be clinically relevant by the investigator (special attention should be given to COVID-19, e.g., fever, dry cough, dyspnea, sore throat, or fatigue).
- Subjects must adhere to the clinical site's house rules, which include, amongst others, polymerase chain reaction testing for SARS-CoV-2 at screening and admission.
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- Legal incapacity or limited legal capacity at screening.
- Additional exclusion criteria for subjects with moderate hepatic impairment (Group 1)
- History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion (ADME) of the study treatment except for those related to liver cirrhosis (appendectomy and herniotomy allowed, cholecystectomy not allowed).
- Hepatic cancer, primary biliary cirrhosis, or any form of cholestatic disease.
- Clinical evidence or suspected acute liver failure as judged by the investigator.
- Encephalopathy grade greater than 2.
- Severe ascites and/or pleural effusion.
- Clinically relevant findings in clinical laboratory tests (hematology, coagulation, clinical chemistry, and urinalysis) at screening \& on Day -1, except for those related to liver cirrhosis.
- Additional exclusion criteria for healthy subjects (Group 2)
- Clinically relevant findings on the physical examination at screening.
- History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion (ADME) of the study treatment (appendectomy and herniotomy allowed, cholecystectomy not allowed).
- Clinically relevant findings in clinical laboratory tests (hematology, coagulation, clinical chemistry, and urinalysis) at screening \& on Day -1.
- Clinically relevant abnormalities on a 12-lead ECG, recorded after 5 min in the supine position at screening \& on Day 1 pre-dose.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: An Open-label Phase 1 Study to Investigate the Effect of Moderate Hepatic Impairment Due to Liver Cirrhosis on the Pharmacokinetics of a Single Dose of 25 mg Aprocitentan
This is a prospective, open-label, single-dose, Phase 1 study, to assess the effect of moderate hepatic impairment due to liver cirrhosis on the pharmacokinetics of aprocitentan (ACT-132577).
- Conditions
- Hepatic Impairment, Healthy Subjects
- Being tested
- Aprocitentan
- Keywords
- Liver Diseases
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AprocitentanDrug
Also called ACT-132577
A single oral dose of 25 mg.
| Study group | Role | What they receive |
|---|---|---|
| Subjects with moderate hepatic impairment (Group 1) | Experimental | Not described Receives: Drug: Aprocitentan |
| Healthy subjects (Group 2) | Experimental | Not described Receives: Drug: Aprocitentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
The maximum plasma concentration (Cmax) of aprocitentan
Measured: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 14.
Area under the plasma concentration-time curves (AUC0-t) of aprocitentan
Measured: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 14.
Area under the plasma concentration-time curve to infinity (AUC0 to inf) of aprocitentan
Measured: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 14.
Secondary outcomes (1)
Treatment-emergent Adverse Events
Measured: From study treatment administration on Day 1 up to last assessment on End of Study (Day 15)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start26 Jun 2020
- Primary completion5 Apr 2021
- Study completion6 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 Hepatic ImpairmentStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Healthy subjects will be matched to subjects with moderate hepatic impairment
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Idorsia Pharmaceuticals Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04252495
- Sponsor's protocol ID
- ID-080-109
- Other IDs
- 2019-003580-21, 2019
- Status last verified
- Nov 2022
- First submitted
- 31 Jan 2020
- Last updated
- 23 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fontes MSC, Dingemanse J, Halabi A, Tomaszewska-Kiecana M, Sidharta PN. Single-dose pharmacokinetics, safety, and tolerability of the dual endothelin receptor antagonist aprocitentan in subjects with moderate hepatic impairment. Sci Rep. 2022 Nov 9;12(1):19067. doi: 10.1038/s41598-022-22470-z.
PubMed 36352054
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Phase 1 Study to Investigate the Effect of Moderate Hepatic Impairment Due to Liver Cirrhosis on the Pharmacokinetics of a Single Dose of 25 mg Aprocitentan
- ClinicalTrials.gov ID
- NCT04252495
- Acronym / sponsor ID
- ID-080-109
- Conditions
- Hepatic Impairment, Healthy Subjects
- Keywords
- Liver Diseases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- 26 Jun 2020 (actual)
- Primary completion
- 5 Apr 2021 (actual)
- Study completion
- 6 May 2021 (actual)
- First posted
- 5 Feb 2020 (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.
This is a prospective, open-label, single-dose, Phase 1 study, to assess the effect of moderate hepatic impairment due to liver cirrhosis on the pharmacokinetics of aprocitentan (ACT-132577).
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Healthy subjects will be matched to subjects with moderate hepatic impairment
| Arm | Type | Receives |
|---|---|---|
| Subjects with moderate hepatic impairment (Group 1) | Experimental | Drug: Aprocitentan |
| Healthy subjects (Group 2) | Experimental | Drug: Aprocitentan |
Who may qualify
- Ages
- 30 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Signed informed consent in a language understandable to the subject prior to any study-mandated procedure.
- Women of childbearing potential (WoCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1 and must agree to use highly effective methods of contraception from screening up to 30 days after study treatment.
- A Women of non-childbearing potential (WoNCBP) must meet one of the following criteria:
- Body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening.
- Normal renal function confirmed by a creatinine clearance at screening according to Cockcroft and Gault adjusted to age.
Key exclusion criteria (19 listed)
- Pregnant or lactating women.
- Previous exposure to aprocitentan and/or macitentan.
- Known hypersensitivity to any excipients of the drug formulation.
- Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
- Any signs or symptoms of active, ongoing infection judged to be clinically relevant by the investigator (special attention should be given to COVID-19, e.g., fever, dry cough, dyspnea, sore throat, or fatigue).
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 |
|---|---|---|
| AprocitentanAlso: ACT-132577A single oral dose of 25 mg. | Drug | Healthy subjects (Group 2), Subjects with moderate hepatic impairment (Group 1) |
Primary outcome
The maximum plasma concentration (Cmax) of aprocitentan
Time frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 14.
Area under the plasma concentration-time curves (AUC0-t) of aprocitentan
Time frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 14.
Area under the plasma concentration-time curve to infinity (AUC0 to inf) of aprocitentan
Time frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 14.
1 secondary outcome
Treatment-emergent Adverse Events
Time frame: From study treatment administration on Day 1 up to last assessment on End of Study (Day 15)
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 23 Nov 2022.
- Derived from this study: PubMed 36352054Fontes MSC, Dingemanse J, Halabi A, Tomaszewska-Kiecana M, Sidharta PN. Single-dose pharmacokinetics, safety, and tolerability of the dual endothelin receptor antagonist aprocitentan in subjects with moderate hepatic impairment. Sci Rep. 2022 Nov 9;12(1):19067. doi: 10.1038/s41598-022-22470-z.
- Individual participant dataSharing planned: No
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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.
Clinical Trials study director
Idorsia Pharmaceuticals Ltd.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Aprocitentan in people with Hepatic Impairment and Healthy Subjects, run by Idorsia Pharmaceuticals Ltd. at 2 sites in 2 countries.
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 15 inclusion and 19 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 23 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany, Poland. 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 maximum plasma concentration (Cmax) of aprocitentan (time frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 14.). The study lists 3 primary outcomes in all. 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 NCT04252495, 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 23 Nov 2022.