A Single Center, Open Label Study of Pharmacokinetics of Clinical Probes and Characteristics of Endogenous Biomarker for Drug-metabolizing Enzymes and Transporters in Chinese Older Adults
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 624
- 试验地点
- 1
- 主要终点
- Level of endogenous biomarker
研究概览
简要总结
The goal of this observational study aims to reveal the pharmacokinetics of clinical probes and characteristics of endogenous biomarkers for drug-metabolizing enzymes and transporters in Chinese older adults and old older adults, to analyze their correlation with frailty, and to explore the exosome characteristics in this population.
详细描述
This study is a non-intervention observational study in Chinese older adults and will not interfere with the routine medical treatment. 6-10 mL whole blood and 20 mL urine samples (only applicable for patients taking meropenem and metformin) will be collected from eligible subjects according to medical routine blood collection time. Concentration of clinical probes and respective metabolites (when required), endogenous biomarkers, genotype information of drug-metabolizing enzymes and transporters, and the exosome characteristics will be quantified or measured.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Other
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Older adults males and females aged 60-74 years old (older adults group) and ≥75 years old (old older adults group), proportion of either sex must not be less than 1/3 (except for subjects taking finasteride), number of subjects in each frailty category must not be less than 10;
- •Male participants must weight ≥45 kg and female participants must weight ≥40 kg. Body mass index (BMI) must be within the range of 18.0-28.0 (inclusive). BMI = weight (kg)/height^2 (m^2);
- •Inpatients with stable underlying disease, who takes any one or more of the following clinical probes: omeprazole/rabeprazole/pantoprazole/metoprolol/carvedilol/rivaroxaban/amlodipine/finasteride/simvastatin/meropenem/atorvastatin/rosuvastatin/metformin;
- •Creatinine clearance (CRCL) ≥15 mL/min, calculated by CockCroft-Gault equation. CRCL = [(140-age)*(lean body weight, kg)*(0.85 if female)/(72*Scr, mg/dL);
- •Willingness to comply with the study protocol and sign informed consent form.
排除标准
- •Subjects with known history of blood phobia or needle phobia that would preclude safe participation in the study procedures.
- •History of disease or an emerging disease within the past 1 month that could affect the study: Diseases affecting the abundance and activity of liver drug enzymes or transporters: cancer, diabetes (except metformin group), acute kidney injury, liver disease (cirrhosis, liver cancer, severe liver injury, severe fatty liver, liver abscess, internal bile duct stones, etc.)
- •History of major diseases or newly discovered diseases: prostate cancer, leukemia, liver cancer, breast cancer, colorectal cancer, leukemia and other tumor diseases;
- •Drugs that may affect the study were consumed within 1 week prior to screening:
- •Patients taking omeprazole/rabeprazole/pantoprazole: Potent CYP2C19 inhibitors: ASP8477, fluconazole, fluoxetine, fluvoxamine, ticlopidine; Potent CYP2C19 inducers: apalutamide, rifampicin, ritonavir;
- •Patients taking metoprolol/carvedilol: Potent CYP2D6 inhibitors: ASP8477, bupropion, fluoxetine, paroxetine, quinidine
- •Patients taking rivaroxaban/amlodipine/finasteride/simvastatin/atorvastatin: Potent CYP3A inhibitor: boceprevir, ceritinib, conivaptan hydrochloride, verapamil, diltiazem, aprepitant, quinidine, dronedarone, tacrolimus, protease inhibitors (ritonavir, indinavir, nelfinavir, saquinavir, lopinavir), macrolides antibiotics (erythromycin, clarithromycin, telithromycin), chloramphenicol, antifungal drugs (ketoconazole, itraconazole, posaconazole, voriconazole, fluconazole, miconazole) nefazoldone, cobistat, cimetidine, ciprofloxacin, fluvoxamine, imatinib, St. John's wort, ranolazine; Potent CYP3A inducers: apalutamide, avomibe, rifampicin, carbamazepine, enzalutamide, ivosidenib, mitotane, phenytoin, rifapentine
- •Patients taking meropenem: Potent OAT inhibitors: aminohippuric acid, probenecid, teriflunomide
- •Patients taking simvastatin/atorvastatin/rosuvastatin: Potent OATP1B1 inhibitor: protease inhibitor (atazanavir, ritonavir, lopinavir, simeprevir), cyclosporin, macrolides antibiotics (erythromycin, clarithromycin), rifampicin;
- •Subjects who have smoking addict or alcohol abuse and do not agree to abstain from smoking or drinking during the trial period (smoking addict: average of ≥5 cigarettes daily; alcohol abuse: average of ≥100mL hard liquor);
- •Tested positive on virological test (human immunodeficiency virus antibody (HIV-Ab)), syphilis serological test, hepatitis B virus surface antigen (HBsAg), or hepatitis C virus antibody (HCV-Ab) within 6 months prior to screening;
- •Subjects who have participated in clinical trials of any drug or medical device within 3 months prior to screening;
- •Subjects who have any factors deemed unsuitable for participation in this study.
研究组 & 干预措施
Older adults
Aged 60-74 years old, takes omeprazole or rabeprazole or pantoprazole or metoprolol or carvedilol or amlodipine or finasteride or simvastatin or rivaroxaban or meropenem or atorvastatin or rosuvastatin or metformin
干预措施: Clinical probes (Drug)
Old older adults
Aged >75 years old, takes omeprazole or rabeprazole or pantoprazole or metoprolol or carvedilol or amlodipine or finasteride or simvastatin or rivaroxaban or meropenem or atorvastatin or rosuvastatin or metformin
干预措施: Clinical probes (Drug)
结局指标
主要结局
Level of endogenous biomarker
时间窗: sampling will be performed according to routine medical follow-up, which should be no less than 3 samples over the period of one year
The level of endogenous biomarker (Dihydroxyeicosatrienoic acids, DHETs, 4β-hydroxycholesterol/cholesterol ratio, 4β-OHC/CHO, pyridoxic acids, PDA, Coproporphyrin, CP) will be quantified and measured by LC-MS/MS or HPLC or ELISA
Concentration of clinical probes in plasma
时间窗: Sampling will be performed according to routine medical follow-up, which should be no less than 3 samples over the period of one year
Plasma concentration of clinical probes and the respective metabolites (when required) will be quantified and measured by LC-MS/MS or HPLC
Concentration of clinical probes in urine
时间窗: Urine samples will be collected at any administration intervals, which should be no less than 1 sample over the period of one year
Urine concentration of meropenem and metformin will be quantified and measured by LC-MS/MS or HPLC
次要结局
未报告次要终点
研究者
Dongyang Liu
Deputy Director Drug Clinical Trial Center
Peking University Third Hospital