Clinical trial NCT06468826: A Study of Avacopan in Participants With Normal Renal Function and Participants With End-Stage Renal Disease (ESRD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: End-Stage Renal Disease (ESRD)
Keywords: End-Stage Renal Disease
ESRD
Renal Function
Hemodialysis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2024-06-21
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Avacopan
timeFrame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36 hours (postdose), Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 12, Day 15, and Day 18.
measure: Cmax of M1
timeFrame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36 hours (postdose), Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 12, Day 15, and Day 18.
measure: Area Under the Plasma Concentration-time Curve (AUC) from Time Zero to Time of Last Quantifiable Concentration (AUClast) of Avacopan
timeFrame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36 hours (postdose), Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 12, Day 15, and Day 18.
measure: AUClast of M1
timeFrame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36 hours (postdose), Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 12, Day 15, and Day 18.
measure: AUC from Time Zero to Infinity (AUCinf) of Avacopan
timeFrame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36 hours (postdose), Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 12, Day 15, and Day 18.
measure: AUCinf of M1
timeFrame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36 hours (postdose), Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 12, Day 15, and Day 18.
measure: AUC from Time Zero to 48 Hours (AUC0-48) of Avacopan
timeFrame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36 hours (postdose), Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 12, Day 15, and Day 18.
measure: AUC0-48 of M1
timeFrame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36 hours (postdose), Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 12, Day 15, and Day 18.
measure: HD Clearance of Drug From Plasma (CLD) of Avacopan
timeFrame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36 hours (postdose), Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 12, Day 15, and Day 18.
measure: HD CLD of M1
timeFrame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36 hours (postdose), Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 12, Day 15, and Day 18.
Secondary outcomes:
measure: Number of Participants who Experienced Treatment-emergent Adverse Events
timeFrame: Up to approximately 37 days.
measure: Number of Participants who Experienced Serious Adverse Events
timeFrame: Up to approximately 96 days.
Other outcomes:
Locations:
city: Miami Lakes
country: United States
facility: Floridian Clinical Research, LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: