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A Study to Evaluate the Pharmacokinetics of Avacopan (CCX168) in Participants With Mild or Moderate Hepatic Impairment

Primary Purpose

Hepatic Impairment

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Avacopan
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Impairment focused on measuring Liver disease, Anti-neutrophil cytoplasmic antibody-associated vasculitis, Complement C5a receptor (C5aR)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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; 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. Inclusion criteria Specific for Healthy Participants: 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. Exclusion Criteria: 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; 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. Exclusion Criteria Specific for Healthy Participants: 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.

Sites / Locations

  • Clinical Pharmacology of Miami, Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Group 1: Mild Hepatic Impairment

Group 2: Moderate Hepatic Impairment

Group 3: Healthy Control Group

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Maximum Plasma Concentration (Cmax) of Avacopan
Cmax of CCX168-M1
Time of Cmax (Tmax) of Avacopan
Tmax of CCX168-M1
Terminal Phase Rate Constant of Avacopan
Terminal Phase Rate Constant of CCX168-M1
Apparent Terminal Half-life (t1/2z) of Avacopan
t1/2z of CCX168-M1
Apparent Oral Clearance (CL/F) of Avacopan
CL/F of CCX168-M1
Apparent Volume of Distribution (Vz/F) of Avacopan
Vz/F of CCX168-M1
Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time t (time of last quantifiable plasma concentration) (AUClast) of Avacopan
AUClast of CCX168-M1
AUC from Time 0 to Time 6 Hours Post-dose (AUC0-6h) of Avacopan
AUC0-6h of CCX168-M1
AUC from Time 0 to Time 12 Hours Post-dose (AUC0-12h) of Avacopan
AUC0-12h of CCX168-M1
AUC from Time 0 to Infinity (AUC0-inf) of Avacopan
AUC0-inf of CCX168-M1

Secondary Outcome Measures

Number of Participants Experiencing Adverse Events

Full Information

First Posted
August 15, 2023
Last Updated
August 15, 2023
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT06004934
Brief Title
A Study to Evaluate the Pharmacokinetics of Avacopan (CCX168) in Participants With Mild or Moderate Hepatic Impairment
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
April 17, 2018 (Actual)
Primary Completion Date
September 18, 2018 (Actual)
Study Completion Date
September 18, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment
Keywords
Liver disease, Anti-neutrophil cytoplasmic antibody-associated vasculitis, Complement C5a receptor (C5aR)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1: Mild Hepatic Impairment
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 2: Moderate Hepatic Impairment
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 3: Healthy Control Group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Avacopan
Other Intervention Name(s)
CCX168
Intervention Description
Administered orally.
Primary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) of Avacopan
Time Frame
Up to Day 18
Title
Cmax of CCX168-M1
Time Frame
Up to Day 18
Title
Time of Cmax (Tmax) of Avacopan
Time Frame
Up to Day 18
Title
Tmax of CCX168-M1
Time Frame
Up to Day 18
Title
Terminal Phase Rate Constant of Avacopan
Time Frame
Up to Day 18
Title
Terminal Phase Rate Constant of CCX168-M1
Time Frame
Up to Day 18
Title
Apparent Terminal Half-life (t1/2z) of Avacopan
Time Frame
Up to Day 18
Title
t1/2z of CCX168-M1
Time Frame
Up to Day 18
Title
Apparent Oral Clearance (CL/F) of Avacopan
Time Frame
Up to Day 18
Title
CL/F of CCX168-M1
Time Frame
Up to Day 18
Title
Apparent Volume of Distribution (Vz/F) of Avacopan
Time Frame
Up to Day 18
Title
Vz/F of CCX168-M1
Time Frame
Up to Day 18
Title
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
Title
AUClast of CCX168-M1
Time Frame
Up to Day 18
Title
AUC from Time 0 to Time 6 Hours Post-dose (AUC0-6h) of Avacopan
Time Frame
Up to Hour 6
Title
AUC0-6h of CCX168-M1
Time Frame
Up to Hour 6
Title
AUC from Time 0 to Time 12 Hours Post-dose (AUC0-12h) of Avacopan
Time Frame
Up to Hour 12
Title
AUC0-12h of CCX168-M1
Time Frame
Up to Hour 12
Title
AUC from Time 0 to Infinity (AUC0-inf) of Avacopan
Time Frame
Up to Day 18
Title
AUC0-inf of CCX168-M1
Time Frame
Up to Day 18
Secondary Outcome Measure Information:
Title
Number of Participants Experiencing Adverse Events
Time Frame
Up to Day 18

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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; 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. Inclusion criteria Specific for Healthy Participants: 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. Exclusion Criteria: 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; 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. Exclusion Criteria Specific for Healthy Participants: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Pharmacology of Miami, Inc.
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33014
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
http://www.amgen.com/datasharing
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

A Study to Evaluate the Pharmacokinetics of Avacopan (CCX168) in Participants With Mild or Moderate Hepatic Impairment

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