A Phase 1, Open-label, Single-dose, Randomized, Crossover Study in Healthy Subjects of the Effects of Co-administration With Food on Exposure, and to Determine the Within-subject Variability in Exposure, to Relacorilant and Its Metabolites
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
研究概览
简要总结
This is an open-label, randomized, single-dose, 3-period crossover, Williams' design, food-interaction (fasted and fed arms) study conducted in healthy subjects.
详细描述
This food-interaction study will be conducted in healthy subjects. Each subject will have a screening visit (within the 21 days prior to the first study drug administration to confirm eligibility), 3 single-dose treatment periods separated by a 7- to 14- day washout between doses, and an outpatient end-of-study follow-up visit 14 +/- 2 days after the last dose of study medication. During each treatment period, subjects will receive a single 350-mg relacorilant dose. Based on randomization to 1 of 6 sequences, each subject will receive the relacorilant dose once after a 10.5 hour fast; once 30 minutes after the start of a high-fat meal; and once 30 minutes after the start of a moderate meal.
During the first treatment period only, regardless of randomized sequence, subjects will report to the clinical research unit on the morning of Day -1 for baseline laboratory assessments and to collect samples for assay of messenger ribonucleic acid (mRNA) expression of glucocorticoid-modulated genes to explore the normal range over the day in healthy subjects. For the subsequent 2 treatment periods, subjects will report to the CRU on the evening of Day -1.
Blood samples for assay of plasma concentration of relacorilant and its main metabolites will be collected pre-dose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, and 96 hours post-dose. Subjects and will remain in the clinic until after the 24-hour blood samples are collected and then be discharged and scheduled to return for the later samples.
Additional samples will be collected for possible future pharmacogenomic analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Able to understand the purpose and risks of the study; willing and able to adhere to scheduled visits, treatment plans, laboratory tests, and other study evaluations and procedures.
- •Give written informed consent.
- •Be males or nonpregnant, nonlactating females judged to be in good health, based on the results of medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory findings.
- •Have a body mass index (BMI) between 18 and 32 kg/m2, inclusive, and a body weight more than 50 kg (110 pounds).
- •Be a nonsmoker. Use of nicotine or nicotine-containing products must be discontinued at least 90 days prior to the first dose of study drug.
- •Be willing to comply with study restrictions
- •Have suitable veins for multiple venipuncture/cannulation.
- •Female subjects must be either of nonchildbearing potential (ie, postmenopausal or permanently sterilized) or use highly effective contraception with low user-dependency.
- •The only acceptable method of highly effective contraception with low user-dependency is an intrauterine device (IUD). Use of hormonal contraception (by any route, including intrauterine hormone releasing systems) or hormone replacement therapy is NOT acceptable.
排除标准
- •Be an employee or immediate family member of the Clinical Research Unit or Corcept.
- •Have been previously enrolled in any study of relacorilant.
- •Have multiple drug allergies, or be allergic to any of the components of relacorilant.
- •Have a condition that could be aggravated by glucocorticoid blockade (eg, asthma, any chronic inflammatory condition).
- •Have a history of gastric bypass surgery.
- •Have a history of malabsorption syndrome or previous gastrointestinal surgery, with the exception of appendectomy and cholecystectomy, which could affect drug absorption or metabolism.
- •Current alcohol or substance abuse.
- •In the 2 calendar months before first study drug administration, have donated/lost blood or plasma in excess of 400 mL.
- •In the 30 days before first study drug administration, have participated in another clinical trial of a new chemical entity or a prescription medicine.
- •Have a positive test for alcohol or drugs of abuse at screening or first admission.
- •Have a positive test for exogenous glucocorticoids at screening.
- •Have clinically relevant abnormal findings on vital signs, physical examination, laboratory screening tests, or 12-lead ECG, at screening and/or before first study drug administration, including but not limited to**:
- •QT interval corrected for heart rate (QTc) using Fridericia's equation (QTcF) >450 ms (from mean of 3 supine ECGs, performed at least 2 minutes apart)
- •Stage 2 or higher hypertension (supine/semi-recumbent systolic blood pressure [SBP] >160 mmHg, diastolic blood pressure [DBP] >100 mmHg; based on mean of duplicate values recorded at least 2 minutes apart)
- •Stage 1 hypertension (supine/semi-recumbent SBP 140-160 mmHg, DBP 90-100 mmHg; based on mean of duplicate values recorded at least 2 minutes apart) associated with indication for treatment ie, evidence of end-organ damage, diabetes, or a 10-year cardiovascular risk, estimated using a standard calculator, (eg, QRISK2-2016) greater than 20%
- •Glomerular filtration rate, estimated using the chronic kidney disease epidemiology (collaboration) (CKD-EPI) method (eGFR; Levey 2009) <60 mL/minute/1.73 m2
- •Hypokalemia (potassium below lower limit of normal)
- •Alanine aminotransferase (ALT), aspartate amino transferase (AST), and/or gamma- glutamyltransferase (GGT) >1.5 times the upper limit of normal (ULN)
- •Seropositive for hepatitis B, hepatitis C, or human immunodeficiency (HIV) viruses **For purposes of qualifying any given subject for study participation, out-of-range values may be repeated once.
- •Have any medical or social reasons for not participating in the study raised by their primary care physician.
- •Have any other condition that might increase the risk to the individual or decrease the chance of obtaining satisfactory data, as assessed by the Investigator.
- •Taken any prohibited prior medication within protocol designated timeframes, such as or including any glucocorticoid, strong inducers, inhibitors or substrates of CYP enzymes involved in drug-drug-interactions, hormonal contraception or hormone replacement therapy.
研究组 & 干预措施
Relacorilant Fasted
Relacorilant Fasted
干预措施: Relacorilant Fasted (Drug)
Relacorilant with a high fat breakfast
Relacorilant with a high fat breakfast
干预措施: Relacorilant with a high fat breakfast (Drug)
Relacorilant with a moderate breakfast
Relacorilant with a moderate breakfast
干预措施: Relacorilant with a moderate breakfast (Drug)
结局指标
主要结局
Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
时间窗: predose to 96 hrs postdose
Ratio of population geometric means (GMR) for Test 1 (standard high fat breakfast) and Reference (fasted) and for Test 2 (standard moderate breakfast) and Reference for relacorilant areas under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
次要结局
- Area under plasma concentration-time curve extrapolated to infinity (AUCinf)(predose to 96 hrs postdose)
- Maximum plasma concentration (Cmax)(predose to 96 hrs postdose)
- ECGs(up to 9 weeks)
- Vital Signs(up to 9 weeks)
- Physical Examinations(up to 9 weeks)
- Adverse Events(up to 9 weeks)
- Safety Labs(up to 9 weeks)