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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Avacopan | Drug | Administered orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Avacopan | Up to Day 18 | |
| Cmax of CCX168-M1 | Up to Day 18 | |
| Time of Cmax (Tmax) of Avacopan | Up to Day 18 | |
| Tmax of CCX168-M1 | Up to Day 18 | |
| Terminal Phase Rate Constant of Avacopan | Up to Day 18 | |
| Terminal Phase Rate Constant of CCX168-M1 | Up to Day 18 | |
| Apparent Terminal Half-life (t1/2z) of Avacopan | Up to Day 18 | |
| t1/2z of CCX168-M1 | Up to Day 18 | |
| Apparent Oral Clearance (CL/F) of Avacopan | Up to Day 18 | |
| CL/F of CCX168-M1 | Up to Day 18 | |
| Apparent Volume of Distribution (Vz/F) of Avacopan | Up to Day 18 | |
| Vz/F of CCX168-M1 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Experiencing Adverse Events | Up to Day 18 |
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Inclusion Criteria:
Inclusion Criteria Specific for Participants with Hepatic Impairment:
Inclusion criteria Specific for Healthy Participants:
Exclusion Criteria:
Exclusion Criteria Specific for Participants with Hepatic Impairment:
Exclusion Criteria Specific for Healthy Participants:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Pharmacology of Miami, Inc. | Hialeah | Florida | 33014 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38993026 | Derived | 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. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
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| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D056648 | Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis |
| ID | Term |
|---|---|
| D004066 | Digestive System Diseases |
| D056647 | Systemic Vasculitis |
| D014657 | Vasculitis |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C000620232 | avacopan |
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| 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 | Up to Day 18 |
| AUClast of CCX168-M1 | Up to Day 18 |
| AUC from Time 0 to Time 6 Hours Post-dose (AUC0-6h) of Avacopan | Up to Hour 6 |
| AUC0-6h of CCX168-M1 | Up to Hour 6 |
| AUC from Time 0 to Time 12 Hours Post-dose (AUC0-12h) of Avacopan | Up to Hour 12 |
| AUC0-12h of CCX168-M1 | Up to Hour 12 |
| AUC from Time 0 to Infinity (AUC0-inf) of Avacopan | Up to Day 18 |
| AUC0-inf of CCX168-M1 | Up to Day 18 |
| D002318 |
| Cardiovascular Diseases |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |