Pharmacokinetics of Clinical Probes and Characteristics of Endogenous Biomarker in Chinese Older Adults

NCT05893849 | Unknown

• 1 other identifier: M2022778
• Study Type: observational
• Target: 624
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Aging

Keywords

Chinese older adults; clinical probes; endogenous biomarkers; drug metabolizing enzymes; drug transporters

Outcome Measures

Primary Outcomes (3)

• Concentration of clinical probes in plasma

  Plasma concentration of clinical probes and the respective metabolites (when required) will be quantified and measured by LC-MS/MS or HPLC

  Sampling will be performed according to routine medical follow-up, which should be no less than 3 samples over the period of one year

• Concentration of clinical probes in urine

  Urine concentration of meropenem and metformin will be quantified and measured by LC-MS/MS or HPLC

  Urine samples will be collected at any administration intervals, which should be no less than 1 sample over the period of one year

• Level of endogenous biomarker

  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

  sampling will be performed according to routine medical follow-up, which should be no less than 3 samples over the period of one year

Study Arms (2)

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

Drug: Clinical probes

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

Drug: Clinical probes

Interventions

Clinical probes DRUG

Inpatients taking one or more clinical probes of CYP2C19 (omeprazole, rabeprazole, pantoprazole), CYP2D6 (metoprolol, carvedilol), CYP3A4 (rivaroxaban, finasteride, amlodipine, simvastatin), OAT (meropenem), OATP1B1 (atorvastatin, rosuvastatin) and OCT (metformin) will be included in the study.

Old older adults; Older adults

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Inpatients aged 60-74 years old (older adults group) and ≥75 years old (old older adults group) with stable underlying disease, takes any one or more of the following clinical probes: omeprazole/rabeprazole/pantoprazole/metoprolol/carvedilol/rivaroxaban/amlodipine/finasteride/simvastatin/meropenem/atorvastatin/rosuvastatin/metformin.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University Third Hospital: lead

Study Sites (1)

Peking University Third Hospital

Beijing, 100191, China

RECRUITING

Study Officials

• Dongyang Liu

  Drug Clinical Trial Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dongyang Liu

CONTACT

(86)010-82266658; liudongyang@vip.sina.com

Cheng Cui

CONTACT

13011825605; cuicheng1226@163.com

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director Drug Clinical Trial Center

Study Record Dates

• First Submitted: March 16, 2023
• First Posted: June 8, 2023
• Study Start: March 28, 2023
• Primary Completion: March 1, 2024
• Study Completion: April 1, 2024
• Last Updated: June 8, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)