An Open-Label, Phase 1 Study in Healthy Volunteers to Evaluate the Drug-Drug Interaction Potential of CCX168 With Concomitant Medications
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Cohort A: Cmax of Celecoxib
研究概览
简要总结
The primary objective of this study will be to evaluate the drug-drug interaction potential of CCX168 with concomitant medications, as either a perpetrator or a victim, following oral administration of CCX168 to healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female participants, aged 18-55 years inclusive, who are in generally good health as judged by the Investigator, whose body mass index is 19.0 to 32.0 kg/m^2 inclusive;
- •Willing and able to give written Informed Consent and to comply with the requirements of the study protocol;
- •Negative result of the human immunodeficiency virus screen, the hepatitis B screen, and the hepatitis C screen;
- •Judged to be healthy by the Investigator, based on medical history, physical examination (including electrocardiogram, and clinical laboratory assessments. Participants with clinical laboratory values that are outside of normal limits and/or with other abnormal clinical findings that are judged by the Investigator not to be of clinical significance may be entered into the study;
- •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.
排除标准
- •Pregnant or breastfeeding;
- •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;
- •For at least 14 days prior to check-in and throughout the blood sample collection period, participants will not be allowed to eat any food or drink any beverage containing alcohol, grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard greens) and charbroiled meats; strenuous exercise must be stopped 4 days prior to check-in;
- •History within the three months prior to check-in of use of tobacco and/or nicotine containing products;
- •History within one year prior to check-in of illicit drug use;
- •History of alcohol abuse at any time in the past;
- •Has 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's hemoglobin less than 11.5 g/dL for women or less than 13.0 g/dL for men, at screening or check-in, confirmed by a repeat measurement;
- •Participated in any clinical study of an investigational product within 30 days prior to dosing or within 5 half-lives after dosing;
- •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, confirmed by a repeat measurement;
- •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: opioids, amphetamines and methamphetamines, cannabinoids, benzodiazepines, barbiturates, cocaine, cotinine, methylenedioxymethamphetamine (MDMA or "ecstasy"), methadone, phencyclidine, tri-cyclic antidepressants, or alcohol (Breathalyzer test allowed for alcohol).
- •Participant is known as a CYP2C9 poor metabolizer.
研究组 & 干预措施
Cohort A
A single dose of 2 mg midazolam (a Cytochrome P450 [CYP]3A4 probe drug) and a single dose of 200 mg celecoxib (a CYP2C9 probe drug) will be given orally concurrently on Day 1 and Day 13. On Day 3 through Day 18, CCX168 will be given orally at 30 mg twice daily (b.i.d.), and a single dose of 30 mg CCX168 will be given in the morning on Day 19. On Day 16 through Day 19, a once daily (q.d.) dose of 200 mg itraconazole (a CYP3A4 inhibitor) will be given orally.
干预措施: CCX168 (Drug)
Cohort A
A single dose of 2 mg midazolam (a Cytochrome P450 [CYP]3A4 probe drug) and a single dose of 200 mg celecoxib (a CYP2C9 probe drug) will be given orally concurrently on Day 1 and Day 13. On Day 3 through Day 18, CCX168 will be given orally at 30 mg twice daily (b.i.d.), and a single dose of 30 mg CCX168 will be given in the morning on Day 19. On Day 16 through Day 19, a once daily (q.d.) dose of 200 mg itraconazole (a CYP3A4 inhibitor) will be given orally.
干预措施: Midazolam (Drug)
Cohort A
A single dose of 2 mg midazolam (a Cytochrome P450 [CYP]3A4 probe drug) and a single dose of 200 mg celecoxib (a CYP2C9 probe drug) will be given orally concurrently on Day 1 and Day 13. On Day 3 through Day 18, CCX168 will be given orally at 30 mg twice daily (b.i.d.), and a single dose of 30 mg CCX168 will be given in the morning on Day 19. On Day 16 through Day 19, a once daily (q.d.) dose of 200 mg itraconazole (a CYP3A4 inhibitor) will be given orally.
干预措施: Celecoxib (Drug)
Cohort A
A single dose of 2 mg midazolam (a Cytochrome P450 [CYP]3A4 probe drug) and a single dose of 200 mg celecoxib (a CYP2C9 probe drug) will be given orally concurrently on Day 1 and Day 13. On Day 3 through Day 18, CCX168 will be given orally at 30 mg twice daily (b.i.d.), and a single dose of 30 mg CCX168 will be given in the morning on Day 19. On Day 16 through Day 19, a once daily (q.d.) dose of 200 mg itraconazole (a CYP3A4 inhibitor) will be given orally.
干预措施: Itraconazole (Drug)
Cohort B
A single dose of 30 mg CCX168 will be given on Day 1 and Day 14, while rifampicin (a CYP3A4 inducer) will be given at 600 mg once daily from Day 4 through Day 17.
干预措施: CCX168 (Drug)
Cohort B
A single dose of 30 mg CCX168 will be given on Day 1 and Day 14, while rifampicin (a CYP3A4 inducer) will be given at 600 mg once daily from Day 4 through Day 17.
干预措施: Rifampicin (Drug)
结局指标
主要结局
Cohort A: Cmax of Celecoxib
时间窗: Up to Day 13
Cohort A: Time of Cmax (Tmax) of Midazolam
时间窗: Up to Day 13
Cohort A: Tmax of Celecoxib
时间窗: Up to Day 13
Cohort A: Apparent Terminal Half Life of Celecoxib
时间窗: Up to Day 13
Cohort A: Cmax of CCX168
时间窗: Day 15 up to Day 19
Cohort A: Tmax of CCX168
时间窗: Day 15 up to Day 19
Cohort A: AUC Over the Dosing Interval of CCX168
时间窗: Day 15 up to Day 19
Cohort A: Maximum Plasma Concentration (Cmax) of Midazolam
时间窗: Up to Day 13
Cohort A: Apparent Terminal Half Life of Midazolam
时间窗: Up to Day 13
Cohort B: Tmax of CCX168
时间窗: Up to Day 14
Cohort B: AUC from Time 0 to infinity of CCX168
时间窗: Up to Day 14
Cohort B: Apparent Terminal Half Life of CCX168
时间窗: Up to Day 14
Cohort A: Area under the plasma concentration-time curve (AUC) from Time 0 to infinity of Midazolam
时间窗: Up to Day 13
Cohort A: AUC from Time 0 to infinity of Celecoxib
时间窗: Up to Day 13
Cohort B: Cmax of CCX168
时间窗: Up to Day 14
次要结局
- Number of Participants Experiencing Adverse Events (AEs)(Up to Day 29)
- Number of Participants Experiencing Clinically Significant Changes in Laboratory Parameters(Up to Day 19)
- Number of Participants Experiencing Clinically Significant Changes in Vital Sign Parameters(Up to Day 19)