End-Stage Renal Disease (ESRD)
Conditions
Keywords
End-Stage Renal Disease, ESRD, Renal Function, Hemodialysis
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).
Interventions
DRUGAvacopan
Oral capsules
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Avacopan | 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 was obtained using noncompartmental analysis. |
| Cmax of Metabolite M1 | 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 was obtained using noncompartmental analysis. |
| Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Avacopan | 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 was obtained using noncompartmental analysis. |
| AUClast of Metabolite M1 | 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 was obtained using noncompartmental analysis. |
| AUC From Time Zero to Infinity (AUCinf) of Avacopan | 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 was obtained using noncompartmental analysis. |
| AUCinf of Metabolite M1 | 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 was obtained using noncompartmental analysis. |
| AUC From Time Zero to 48 Hours (AUC0-48) of Avacopan | 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 was obtained using noncompartmental analysis. |
| AUC0-48 of Metabolite M1 | 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 was obtained using noncompartmental analysis. |
| Dialysate Clearance (CLD) of Avacopan | Group 2, Period 1: 0.5, 1, 2 and 3 hours after start of HD and after end of HD at Day 1 | CLD determines how much of the drug is removed by hemodialysis. |
| CLD of Metabolite M1 | Group 2, Period 1: 0.5, 1, 2 and 3 hours after start of HD and after end of HD at Day 1 | CLD determines how much of the drug is removed by hemodialysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug to end of study (EOS) (up to 36 days) | 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. |
| Number of Participants Who Experienced Serious Adverse Events (SAEs) | From signing the informed consent form (ICF) to 30 days after EOS (up to 96 days) | 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. |
Countries
United States
Contacts
STUDY_DIRECTORMD
Amgen
Participant flow
Recruitment details
This study was conducted as a multicenter study in the United States between 18 June 2024 and 05 October 2024.
Pre-assignment details
Participants were assigned to one of two groups: participants with normal renal function (Group 1) and participants with ESRD requiring hemodialysis (HD) (Group 2). Group 1 received a single dose of avacopan on Day 1. In Group 2, avacopan was given on Day 1 of Period 1 and Day 1 of Period 2. Each period lasted 18 days.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 55.5 years STANDARD_DEVIATION 6.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 2 / 6 | 2 / 7 | 0 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 | 0 / 7 |
Outcome results
None listed