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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Maximum Plasma Concentration (Cmax) of Avacopan
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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 -
- •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.
研究组 & 干预措施
Group 1: Mild Hepatic Impairment
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.
干预措施: Avacopan (Drug)
Group 2: Moderate Hepatic Impairment
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.
干预措施: Avacopan (Drug)
Group 3: Healthy Control Group
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.
干预措施: Avacopan (Drug)
结局指标
主要结局
Maximum Plasma Concentration (Cmax) of Avacopan
时间窗: Up to Day 18
Cmax of CCX168-M1
时间窗: Up to Day 18
Time of Cmax (Tmax) of Avacopan
时间窗: Up to Day 18
Tmax of CCX168-M1
时间窗: Up to Day 18
Terminal Phase Rate Constant of Avacopan
时间窗: Up to Day 18
Terminal Phase Rate Constant of CCX168-M1
时间窗: Up to Day 18
Apparent Terminal Half-life (t1/2z) of Avacopan
时间窗: Up to Day 18
t1/2z of CCX168-M1
时间窗: Up to Day 18
Apparent Oral Clearance (CL/F) of Avacopan
时间窗: Up to Day 18
CL/F of CCX168-M1
时间窗: Up to Day 18
Apparent Volume of Distribution (Vz/F) of Avacopan
时间窗: Up to Day 18
Vz/F of CCX168-M1
时间窗: 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
时间窗: Up to Day 18
AUClast of CCX168-M1
时间窗: Up to Day 18
AUC from Time 0 to Time 6 Hours Post-dose (AUC0-6h) of Avacopan
时间窗: Up to Hour 6
AUC0-6h of CCX168-M1
时间窗: Up to Hour 6
AUC from Time 0 to Time 12 Hours Post-dose (AUC0-12h) of Avacopan
时间窗: Up to Hour 12
AUC0-12h of CCX168-M1
时间窗: Up to Hour 12
AUC from Time 0 to Infinity (AUC0-inf) of Avacopan
时间窗: Up to Day 18
AUC0-inf of CCX168-M1
时间窗: Up to Day 18
次要结局
- Number of Participants Experiencing Adverse Events(Up to Day 18)