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

Recruiting

• Conditions: Aging
• Interventions: Drug: Clinical probes

• Registration Number: NCT05893849
• Lead Sponsor: Peking University Third Hospital

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2023-03-16
• Study Start: 2023-03-28
• Status Verified: 2023-06
• Study First Submitted QC: 2023-06-07
• Last Update Submitted: 2023-06-07
• Study First Posted: 2023-06-08
• Last Update Posted: 2023-06-08
• Primary Completion: 2024-03
• Study Completion: 2024-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 624

Inclusion Criteria

1. 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;
2. 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);
3. 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;
4. 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);
5. Willingness to comply with the study protocol and sign informed consent form.

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Exclusion Criteria

1. Subjects with known history of blood phobia or needle phobia that would preclude safe participation in the study procedures.

2. 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.)

3. History of major diseases or newly discovered diseases: prostate cancer, leukemia, liver cancer, breast cancer, colorectal cancer, leukemia and other tumor diseases;

4. 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;

5. 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);

6. 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;

7. Subjects who have participated in clinical trials of any drug or medical device within 3 months prior to screening;

8. Subjects who have any factors deemed unsuitable for participation in this study.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Older adults	Clinical probes	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
Old older adults	Clinical probes	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

Primary Outcome Measures

Name	Time	Method
Level of endogenous biomarker	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	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	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

Trial Locations

Locations (1)

Peking University Third Hospital; 🇨🇳 Beijing, China