Hepatic ImpairmentPhase 1NCT06004934
A Study to Evaluate the Pharmacokinetics of Avacopan (CCX168) in Participants With Mild or Moderate Hepatic Impairment
A Phase 1 study testing Avacopan in people with Hepatic Impairment, run by Amgen at 1 site in United States.
Trial summary
The primary objective of this study will be to evaluate the pharmacokinetic properties of avacopan and its metabolite CCX168-M1 after a single oral dose of 30 mg avacopan in participants with mild or moderate hepatic impairment compared to matched healthy controls. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- Avacopan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Apr 2018to 18 Sep 2018
- 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 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- An Institutional Review Board approved informed consent form is signed and dated prior to any study-related activities;
- Adult male or female participants, aged ≥18 to ≤75 years of age inclusive;
- Body mass index (BMI) ≥18.0 to ≤38.0 kg/m^2, inclusive, at screening;
- Female participants of childbearing potential or male participants with partners of childbearing potential may participate if adequate contraception is used during, and for at least 90 days after, any administration of study medication.
- Inclusion Criteria Specific for Participants with Hepatic Impairment:
- Hepatic disease based on a documented history of hepatic insufficiency with features of cirrhosis and ability to classify hepatic disease as mild or moderate using C-P criteria;
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- No acute episodes of illness related to hepatic insufficiency within 30 days prior to screening, and no significant change in disease status from screening to check-in (Day -1);
- On a stable medication regimen, defined as not starting any new prescription or non-prescription medications or significant changes in dose of such medications within 30 days prior to dosing of investigational drug on Day 1;
- Abnormal laboratory values must be clinically acceptable, as judged by the Investigator;
- Negative result of the human immunodeficiency virus (HIV) screen and the hepatitis B screen. Note hepatically impaired participants with chronic hepatitis C infection (duration > 6 months) are eligible for enrollment, if stable.
- Participants must meet demographically-matched criteria to one of the participants enrolled in this study with moderate hepatic impairment based on sex, age (±10 years), and BMI (±20%);
- Medically normal with no clinically significant illness or disease and no significant abnormal findings at the baseline physical examination;
- Participant has normal (or abnormal and clinically insignificant) laboratory values at screening. A single test repeat at the discretion of the Investigator is allowed during the screening period to determine eligibility;
- Negative result from the HIV screen, the hepatitis B screen, and the hepatitis C screen.
Who cannot join
- Pregnant or breastfeeding;
- At least 7 days prior to check-in, and throughout the blood sample collection period, consumption of any food or any beverage containing grapefruit or grapefruit juice, Seville oranges, apple or orange juice, vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, cauliflower, Brussels sprouts, mustard greens) and charbroiled meats;
- Strenuous exercise within 4 days prior to check-in;
- Recent history of myopathy or muscle injury;
- Consumption of alcohol within 48 hours prior to check-in on Day -1 (as confirmed by alcohol test);
- A history or presence of any form of cancer within the 5 years prior to check-in, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis;
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- History or presence of unexplained syncope or family history of sudden death, or any medical condition or disease which, in the opinion of the Investigator, may place the participant at unacceptable risk for study participation;
- Donated or lost more than 350 mL of blood or blood products within 56 days prior to screening, or donated plasma within 7 days of dosing;
- Participant has any evidence of renal impairment; serum creatinine greater than 1.5 times the upper limit of normal at screening or check-in;
- Participant's urine tested positive at screening and/or check-in for any of the following (unless the positive drug screen in hepatic participants is due to prescription drug use and is approved by the investigator and the Sponsor's Medical Monitor): opioids, amphetamines and methamphetamines, cannabinoids, benzodiazepines, barbiturates, cocaine, cotinine (healthy participants only), methylenedioxymethamphetamine (MDMA or "ecstasy"), methadone, phencyclidine, tri-cyclic antidepressants, or alcohol;
- Currently taking a strong inducer of the cytochrome P450 3A4 (CYP3A4) enzyme, (e.g. carbamazepine, phenobarbital, phenytoin, rifampin, or St. John's wort) or use of a strong CYP3A4 inducer within 14 days prior to check-in and through discharge, unless deemed acceptable by the Investigator, Medical Monitor, and/or the Sponsor;
- Currently taking a strong inhibitor of the CYP3A4 enzyme, (e.g. boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, or voriconazoleor) or use of a strong CYP3A4 inhibitor within 14 days prior to check-in and through discharge, unless deemed acceptable by the Investigator, Medical Monitor, and/or the Sponsor;
- Participated in any clinical study of an investigational product within 30 days prior to dosing or within 5 half-lives after dosing;
- History within one year prior to check-in of illicit drug abuse;
- Significant infection or hospitalization within 28 days prior to check-in on Day -1.
- Exclusion Criteria Specific for Participants with Hepatic Impairment:
- Currently on transplant list or history of portal shunts, recent variceal bleeds, or evidence of hepatorenal syndrome;
- History of prior liver transplant;
- For participants who are smokers, inability to restrict smoking to no more than 10 cigarettes per day from the screening visit until the last outpatient visit.
- Used a prescription and/or over-the-counter medication, with the exception of ibuprofen, hormonal contraceptives, and multi-vitamins, within 14 days prior to check-in; herbal supplements must be stopped 7 days prior to check-in;
- Participant's hemoglobin less than 11.5 g/dL for women or less than 13.0 g/dL for men, at screening or check-in, considered clinically significant by the investigator;
- Participant has any evidence of hepatic disease; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or bilirubin greater than 1.5 times the upper limit of normal at screening or check-in;
- Participant's white blood cell count is below the lower limit of normal at screening or check-in, considered clinically significant by the investigator;
- Participant has used tobacco- or nicotine-containing products (e.g. cigarette, pipe, cigar, chewing, nicotine patch, or nicotine gum) within 6 months prior to check-in on Day -1.
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical Pharmacology of Miami, Inc.
Hialeah, Florida, 33014
About this study
Official title: An Open-Label, Phase 1 Study to Evaluate the Single-dose Pharmacokinetics of Avacopan (CCX168) in Male and Female Subjects With Mild or Moderate Hepatic Impairment
The primary objective of this study will be to evaluate the pharmacokinetic properties of avacopan and its metabolite CCX168-M1 after a single oral dose of 30 mg avacopan in participants with mild or moderate hepatic impairment compared to matched healthy controls.
- Conditions
- Hepatic Impairment
- Being tested
- Avacopan
- Keywords
- Liver disease, Anti-neutrophil cytoplasmic antibody-associated vasculitis, Complement C5a receptor (C5aR)
- Medical subject headings
- Liver Diseases, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvacopanDrug
Also called CCX168
Administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Mild Hepatic Impairment | Experimental | Participants with mild hepatic impairment (defined using Child-Pugh Classification of the Severity of Liver Disease [C-P] criteria [C-P Class A, score of 5 to 6 points]) will receive a single oral dose of 30 mg avacopan on Day 1 in the fasted state. Receives: Drug: Avacopan |
| Group 2: Moderate Hepatic Impairment | Experimental | Participants with moderate hepatic impairment (defined using the C-P criteria [C-P Class B, score of 7 to 9 points]) will receive a single oral dose of 30 mg avacopan on Day 1 in the fasted state. Receives: Drug: Avacopan |
| Group 3: Healthy Control Group | Active comparator | Participants with normal hepatic function (medically normal with no clinically significant illness or disease or abnormal physical examination findings, and with normal laboratory values at screening) will be demographically-matched to participants in Group 1 and Group 2, and will receive a single oral dose of 30 mg avacopan on Day 1 in the fasted state. Receives: Drug: Avacopan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Plasma Concentration (Cmax) of Avacopan
Measured: Up to Day 18
Cmax of CCX168-M1
Measured: Up to Day 18
Time of Cmax (Tmax) of Avacopan
Measured: Up to Day 18
Tmax of CCX168-M1
Measured: Up to Day 18
Terminal Phase Rate Constant of Avacopan
Measured: Up to Day 18
Terminal Phase Rate Constant of CCX168-M1
Measured: Up to Day 18
Apparent Terminal Half-life (t1/2z) of Avacopan
Measured: Up to Day 18
t1/2z of CCX168-M1
Measured: Up to Day 18
Apparent Oral Clearance (CL/F) of Avacopan
Measured: Up to Day 18
CL/F of CCX168-M1
Measured: Up to Day 18
Apparent Volume of Distribution (Vz/F) of Avacopan
Measured: Up to Day 18
Vz/F of CCX168-M1
Measured: Up to Day 18
Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time t (time of last quantifiable plasma concentration) (AUClast) of Avacopan
Measured: Up to Day 18
AUClast of CCX168-M1
Measured: Up to Day 18
AUC from Time 0 to Time 6 Hours Post-dose (AUC0-6h) of Avacopan
Measured: Up to Hour 6
AUC0-6h of CCX168-M1
Measured: Up to Hour 6
AUC from Time 0 to Time 12 Hours Post-dose (AUC0-12h) of Avacopan
Measured: Up to Hour 12
AUC0-12h of CCX168-M1
Measured: Up to Hour 12
AUC from Time 0 to Infinity (AUC0-inf) of Avacopan
Measured: Up to Day 18
AUC0-inf of CCX168-M1
Measured: Up to Day 18
Secondary outcomes (1)
Number of Participants Experiencing Adverse Events
Measured: Up to Day 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2023
- Study start17 Apr 2018
- Primary completion18 Sep 2018
- Study completion18 Sep 2018
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.
- More trials run by AmgenThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06004934
- Sponsor's protocol ID
- CL013_168
- Status last verified
- Jul 2023
- First submitted
- 15 Aug 2023
- Last updated
- 22 Aug 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Publications
Miao S, Suso P, Furst JA, Hudson MG, Trivedi A. Effect of Mild or Moderate Hepatic Impairment on the Pharmacokinetics of Avacopan, a Small-Molecule Complement C5a Receptor Antagonist, for the Treatment of Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis. Clin Pharmacol Drug Dev. 2024 Sep;13(9):1000-1010. doi: 10.1002/cpdd.1444. Epub 2024 Jul 11.
PubMed 38993026
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase 1 Study to Evaluate the Single-dose Pharmacokinetics of Avacopan (CCX168) in Male and Female Subjects With Mild or Moderate Hepatic Impairment
- ClinicalTrials.gov ID
- NCT06004934
- Acronym / sponsor ID
- CL013_168
- Conditions
- Hepatic Impairment
- Keywords
- Liver disease, Anti-neutrophil cytoplasmic antibody-associated vasculitis, Complement C5a receptor (C5aR)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 17 Apr 2018 (actual)
- Primary completion
- 18 Sep 2018 (actual)
- Study completion
- 18 Sep 2018 (actual)
- First posted
- 22 Aug 2023 (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 study will be to evaluate the pharmacokinetic properties of avacopan and its metabolite CCX168-M1 after a single oral dose of 30 mg avacopan in participants with mild or moderate hepatic impairment compared to matched healthy controls.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: Mild Hepatic Impairment | Experimental | Drug: AvacopanParticipants with mild hepatic impairment (defined using Child-Pugh Classification of the Severity of Liver Disease [C-P] criteria [C-P Class A, score of 5 to 6 points]) will receive a single oral dose of 30 mg avacopan on Day 1 in the fasted state. |
| Group 2: Moderate Hepatic Impairment | Experimental | Drug: AvacopanParticipants with moderate hepatic impairment (defined using the C-P criteria [C-P Class B, score of 7 to 9 points]) will receive a single oral dose of 30 mg avacopan on Day 1 in the fasted state. |
| Group 3: Healthy Control Group | Active comparator | Drug: AvacopanParticipants with normal hepatic function (medically normal with no clinically significant illness or disease or abnormal physical examination findings, and with normal laboratory values at screening) will be demographically-matched to participants in Group 1 and Group 2, and will receive a single oral dose of 30 mg avacopan on Day 1 in the fasted state. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- An Institutional Review Board approved informed consent form is signed and dated prior to any study-related activities;
- Adult male or female participants, aged ≥18 to ≤75 years of age inclusive;
- Body mass index (BMI) ≥18.0 to ≤38.0 kg/m^2, inclusive, at screening;
- Female participants of childbearing potential or male participants with partners of childbearing potential may participate if adequate contraception is used during, and for at least 90 days after, any administration of study medication.
- Hepatic disease based on a documented history of hepatic insufficiency with features of cirrhosis and ability to classify hepatic disease as mild or moderate using C-P criteria;
Key exclusion criteria (24 listed)
- Pregnant or breastfeeding;
- At least 7 days prior to check-in, and throughout the blood sample collection period, consumption of any food or any beverage containing grapefruit or grapefruit juice, Seville oranges, apple or orange juice, vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, cauliflower, Brussels sprouts, mustard greens) and charbroiled meats;
- Strenuous exercise within 4 days prior to check-in;
- Recent history of myopathy or muscle injury;
- Consumption of alcohol within 48 hours prior to check-in on Day -1 (as confirmed by alcohol test);
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 |
|---|---|---|
| AvacopanAlso: CCX168Administered orally. | Drug | Group 1: Mild Hepatic Impairment, Group 2: Moderate Hepatic Impairment, Group 3: Healthy Control Group |
Primary outcome
Maximum Plasma Concentration (Cmax) of Avacopan
Time frame: Up to Day 18
Cmax of CCX168-M1
Time frame: Up to Day 18
Time of Cmax (Tmax) of Avacopan
Time frame: Up to Day 18
Tmax of CCX168-M1
Time frame: Up to Day 18
Terminal Phase Rate Constant of Avacopan
Time frame: Up to Day 18
Terminal Phase Rate Constant of CCX168-M1
Time frame: Up to Day 18
Apparent Terminal Half-life (t1/2z) of Avacopan
Time frame: Up to Day 18
t1/2z of CCX168-M1
Time frame: Up to Day 18
Apparent Oral Clearance (CL/F) of Avacopan
Time frame: Up to Day 18
CL/F of CCX168-M1
Time frame: Up to Day 18
Apparent Volume of Distribution (Vz/F) of Avacopan
Time frame: Up to Day 18
Vz/F of CCX168-M1
Time frame: Up to Day 18
Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time t (time of last quantifiable plasma concentration) (AUClast) of Avacopan
Time frame: Up to Day 18
AUClast of CCX168-M1
Time frame: Up to Day 18
AUC from Time 0 to Time 6 Hours Post-dose (AUC0-6h) of Avacopan
Time frame: Up to Hour 6
AUC0-6h of CCX168-M1
Time frame: Up to Hour 6
AUC from Time 0 to Time 12 Hours Post-dose (AUC0-12h) of Avacopan
Time frame: Up to Hour 12
AUC0-12h of CCX168-M1
Time frame: Up to Hour 12
AUC from Time 0 to Infinity (AUC0-inf) of Avacopan
Time frame: Up to Day 18
AUC0-inf of CCX168-M1
Time frame: Up to Day 18
1 secondary outcome
Number of Participants Experiencing Adverse Events
Time frame: Up to Day 18
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 22 Aug 2023.
- Derived from this study: PubMed 38993026Miao S, Suso P, Furst JA, Hudson MG, Trivedi A. Effect of Mild or Moderate Hepatic Impairment on the Pharmacokinetics of Avacopan, a Small-Molecule Complement C5a Receptor Antagonist, for the Treatment of Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis. Clin Pharmacol Drug Dev. 2024 Sep;13(9):1000-1010. doi: 10.1002/cpdd.1444. Epub 2024 Jul 11.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
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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.
MD study director
Amgen
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 Avacopan in people with Hepatic Impairment, run by Amgen 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 14 inclusion and 24 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 22 Aug 2023. 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?
Maximum Plasma Concentration (Cmax) of Avacopan (time frame: Up to Day 18). The study lists 20 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 NCT06004934, 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 22 Aug 2023.