A Study of Avacopan in Participants With Normal Renal Function and Participants With End-Stage Renal Disease (ESRD)

A Phase 1, Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Avacopan in Subjects With Normal Renal Function and Subjects With End-Stage Renal Disease (ESRD) Requiring Hemodialysis

The primary objective of the study is to evaluate the pharmacokinetics (PK) of avacopan and metabolite (M1) after a single dose of avacopan in participants with normal renal function and participants with ESRD requiring hemodialysis (HD).

Study Overview

• Status: Completed
• Conditions: End-Stage Renal Disease (ESRD)
• Intervention / Treatment: Drug: Avacopan

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami Lakes, Florida, United States, 33016
      • Floridian Clinical Research, LLC
    • Orlando, Florida, United States, 32809-3017
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Participant has provided informed consent.
• Male or female participants, between 18 and 75 years of age (inclusive) at the time of Screening.
• Body mass index between 18 and <40 kg/m^2 at the time of Screening.

• Eligible participants will be classified based on established need for renal replacement therapy and estimated glomerular filtration rate (eGFR).

  1. Group 1 (normal renal function): eGFR ≥90 mL/min and no history of renal disease.
  2. Group 2 (ESRD requiring HD): eGFR <15 mL/min and receiving HD.

Exclusion Criteria

All Participants:

• History of uncontrolled or unstable cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematopoietic, psychiatric, or neurological disease, or evidence of rapidly deteriorating renal function.
• History or evidence, at Screening or Check-in, of clinically significant disorder, condition, or disease not otherwise excluded that, in the opinion of the Investigator (or designee), would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
• Total white blood cell count is below the lower limit of normal at Screening or Check-in.
• Significant infection within 28 days before Check-in.
• Prior infection with or exposure to tuberculosis, or travel to areas of endemic tuberculosis or endemic mycoses within the past 6 months.
• Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase or alanine aminotransferase > the upper limit of normal for Group 1 (normal renal function) and >2 times the upper limit of normal for Group 2 (ESRD requiring HD).
• History or evidence, at Screening or Check-in, of poorly controlled diabetes (regardless of type), based on hemoglobin A1C of >10%.
• Clinically significant hyperkalemia (defined by serum potassium concentration as >5.5 mEq/L for Group 1 [normal renal function], >6 mEq/L for Group 2 [ESRD requiring HD]) at Screening or Check-in.
• Participants who have a current, functioning organ transplant and/or are on immunosuppressants.
• Participants on the national transplant list (United Network for Organ Sharing) at Screening who anticipate receiving an organ transplant within 4 months.
• Positive human immunodeficiency virus test.
• Positive hepatitis B or hepatitis C panel at Screening. Participants whose results are compatible with prior hepatitis B infection (positive hepatitis B surface antibody, positive hepatitis B core antibody, or negative HBsAg) will be excluded. Participants whose results are compatible with prior hepatitis B vaccination may be included.
• History or evidence of clinically significant arrhythmia at Screening, including any clinically significant findings on the ECG taken at Check-in.
• History suggestive of esophageal (including esophageal spasm, esophagitis), gastric, or duodenal ulceration, or bowel disease (including but not limited to peptic ulceration, gastrointestinal bleeding, ulcerative colitis, Crohn's disease, or irritable bowel syndrome); or a history of gastrointestinal surgery, other than uncomplicated appendectomy.
• Female participants with a positive pregnancy test at Screening or Check-in.
• Female participants lactating/breastfeeding or who plan to breastfeed during the study through 60 days after administration of investigational product.

Participants in Group 1 (normal renal function) are excluded if:

• History of malignancy of any type, with the exception of the following: in situ cervical cancer or surgically excised non-melanomatous skin cancers more than 5 years before receiving avacopan.
• A corrected QT interval by Fredericia (QTcF) >450 msec in males or >470 msec in females or history/evidence of long QT syndrome at Screening or Check-in.
• A history of renal disease or renal injury as indicated by medical history or an abnormal renal function profile at Screening or Check-in.

Participants in Group 2 (ESRD requiring HD) are excluded if:

• Child-Pugh classification of Class C. Child-Pugh will only be evaluated for participants deemed to have active liver disease by the Investigator (or designee).
• Active malignancy of any type.
• A change in disease status within 30 days of Screening, as documented by the participants medical history, deemed clinically significant by the Investigator.
• A QTcF ≥470 msec in males or ≥480 msec in females.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Normal Renal Function; Participants in Group 1 will receive a single dose of avacopan on Day 1.	Drug: Avacopan; Oral capsules; Other Names: CCX168; AMG 569; Tavneos
Experimental: Group 2: ESRD Requiring HD; Participants in Group 2 will receive a single dose of avacopan on Day 1 in each of 2 treatment periods (Period 1/on HD and Period 2/off HD).	Drug: Avacopan; Oral capsules; Other Names: CCX168; AMG 569; Tavneos

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Avacopan	Cmax was obtained using noncompartmental analysis.	Group 1, Period 1: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36 hours, Days 3,4,5,6,7,8,12,15, and 18 postdose; Group 2, Periods 1 and 2: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36 hours, Days 3,4,5,6,7,8,12,15, and 18 postdose
Cmax of Metabolite M1	Cmax was obtained using noncompartmental analysis.	Group 1, Period 1: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36 hours, Days 3,4,5,6,7,8,12,15, and 18 postdose; Group 2, Periods 1 and 2: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36 hours, Days 3,4,5,6,7,8,12,15, and 18 postdose
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Avacopan	AUClast was obtained using noncompartmental analysis.	Group 1, Period 1: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36 hours, Days 3,4,5,6,7,8,12,15, and 18 postdose; Group 2, Periods 1 and 2: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36 hours, Days 3,4,5,6,7,8,12,15, and 18 postdose
AUClast of Metabolite M1	AUClast was obtained using noncompartmental analysis.	Group 1, Period 1: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36 hours, Days 3,4,5,6,7,8,12,15, and 18 postdose; Group 2, Periods 1 and 2: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36 hours, Days 3,4,5,6,7,8,12,15, and 18 postdose
AUC From Time Zero to Infinity (AUCinf) of Avacopan	AUCinf was obtained using noncompartmental analysis.	Group 1, Period 1: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36 hours, Days 3,4,5,6,7,8,12,15, and 18 postdose; Group 2, Periods 1 and 2: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36 hours, Days 3,4,5,6,7,8,12,15, and 18 postdose
AUCinf of Metabolite M1	AUCinf was obtained using noncompartmental analysis.	Group 1, Period 1: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36 hours, Days 3,4,5,6,7,8,12,15, and 18 postdose; Group 2, Periods 1 and 2: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36 hours, Days 3,4,5,6,7,8,12,15, and 18 postdose
AUC From Time Zero to 48 Hours (AUC0-48) of Avacopan	AUC0-48 was obtained using noncompartmental analysis.	Group 1, Period 1: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36, and 48 hours postdose; Group 2, Periods 1 and 2: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36, and 48 hours postdose
AUC0-48 of Metabolite M1	AUC0-48 was obtained using noncompartmental analysis.	Group 1, Period 1: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36, and 48 hours postdose; Group 2, Periods 1 and 2: predose, 0.25,0.5,1,2,3,4,6,9,12,16,24,36, and 48 hours postdose
Dialysate Clearance (CLD) of Avacopan	CLD determines how much of the drug is removed by hemodialysis.	Group 2, Period 1: 0.5, 1, 2 and 3 hours after start of HD and after end of HD at Day 1
CLD of Metabolite M1	CLD determines how much of the drug is removed by hemodialysis.	Group 2, Period 1: 0.5, 1, 2 and 3 hours after start of HD and after end of HD at Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	An adverse event was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) that was temporally associated with the use of a treatment, combination product, medical device, or procedure. A TEAEs was defined as an AE that started during or after first dose administration or started prior to first dose administration and increased in severity after dosing.	From first dose of study drug to end of study (EOS) (up to 36 days)
Number of Participants Who Experienced Serious Adverse Events (SAEs)	A SAE was defined as any untoward medical occurrence that met at least 1 of the following criteria: results in death, is immediately life-threatening, required inpatient hospitalization or prolonged existing hospitalization, persistent or significant incapacity/disability, a congenital abnormality/birth defect, or other medically important serious event.	From signing the informed consent form (ICF) to 30 days after EOS (up to 96 days)

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2024
• Primary Completion (Actual): October 5, 2024
• Study Completion (Actual): October 5, 2024

Study Registration Dates

• First Submitted: June 17, 2024
• First Submitted That Met QC Criteria: June 17, 2024
• First Posted (Actual): June 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: ESRD; Hemodialysis; Renal Function; End-Stage Renal Disease
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Pathological Conditions, Signs and Symptoms; Kidney Failure, Chronic; avacopan
• Other Study ID Numbers: 20230265

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No