Understanding drug metabolism in older Chinese adults

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

This study is trying to see how older Chinese adults process medications and how this relates to their health and frailty by looking at their blood and urine samples.

Quick facts

• Study type: Observational
• Enrollment: 624 (estimated)
• Ages: 60 Years and up
• Sex: All
• Sponsor: Peking University Third Hospital (Academic / other)
• Drugs / interventions: ceritinib, imatinib
• Locations: 1 site (Beijing)
• Trial ID: NCT05893849 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate the pharmacokinetics of clinical probes and the characteristics of endogenous biomarkers related to drug-metabolizing enzymes and transporters in older Chinese adults. It will analyze the correlation between these factors and frailty, while also exploring the characteristics of exosomes in this population. Blood and urine samples will be collected from participants who are already receiving specific medications, allowing researchers to measure various biomarkers without interfering with their routine medical care.

Who should consider this trial

Good fit: Ideal candidates are older adults aged 60 years and above, who are hospitalized and stable with underlying diseases, and are taking specific clinical probes.

Not a fit: Patients who are younger than 60 years or those not taking the specified clinical probes may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance the understanding of drug metabolism in older adults, leading to improved medication management and personalized treatment strategies.

How similar studies have performed: While there have been studies on drug metabolism in older adults, this specific focus on Chinese older adults and the correlation with frailty is relatively novel.

Eligibility criteria

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.

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.

Where this trial is running

Beijing

• Peking University Third Hospital — Beijing, China (Recruiting)

Study contacts

• Principal investigator: Dongyang Liu — Drug Clinical Trial Center
• Study coordinator: Dongyang Liu

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