1. Chronic kidney disease 2. Elderly 3. Pharmacokinetics 4. Cytochrome P 450 5. Drug transporter 1. Chronic kidney disease (CKD) 2. Elderly 3. Pharmacokinetics (PK) 4. Cytochrome P 450 (CYP450) 5. Drug transporter 6. OATP1B1 7. BCRP
Conditions
Interventions
Microdose cocktail composes of Midazolam,
pitavastatin,
atorvastatin,
rosuvastatin,
dabigatran etexelate will be diluted with lactose to subtherapeutic microdose (30 mcg,
10 mcg,
100 mcg,
50 mcg,
and 750 mcg,
respectively)
subject in arm 1 will receive microdose cocktail in period 1 and receive microdose cocktail with rifampicin in period 2. (wash out period 14 days)
In each period,
plasma sample will be collected at following time points: before dosing (predose),
0.33,
0.67,
1.5,
Sponsors
Health Systems Research Institute
Health Systems Research Institute
Eligibility
Sex/Gender
All
Age
20 Years to 90 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria Group 1 healthy young subjects 1 Subjects who are Thai male or female, aged 20 to 40 years (inclusive). 2 Subjects whose BMI is 18-25 kg/m2 (inclusive). 3 Subjects who are healthy by medical history, physical examination and vital signs. 4 Subject whose screening visit laboratory values of blood tests including complete blood count, fasting blood sugar, blood urea nitrogen, serum creatinine, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, alpha-1-acid glycoprotein, total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, electrolytes, parathyroid hormone, Hepatitis Bs-antigen, anti-HIV are within the normal range or showing no clinically significant abnormalities as confirmed by the clinical investigator. 5 eGFR ≥90 ml/min/1.73 m2 as calculated by eGFR for Thai(73) 6 For female subjects: Female subject who is in childbearing potential must have serum β-HCG negative and agrees to use an acceptable birth control method from visit 1 to the last visit. The acceptable birth control method is defined as a barrier method of contraception (including condoms, intrauterine device (IUD) and diaphragm with spermicidal agent) or total abstinence from sexual intercourse from visit 1 to the last visit. Hormonal contraceptives are not acceptable. Female subject who is in child bearing potential must agree not to become pregnant for the entire participation phase and must have a negative result for urine pregnancy test performing prior to dosing at phase I and phase II. Female subjects can be those with non-childbearing potential which defined as female subjects with hysterectomy, both ovaries removed, surgically sterilized. 7 Subjects are able to understand the requirements of the study and voluntarily sign and date an informed consent, approved by the Independent Ethic Committee (IEC)/ Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures. Group 2: the relatively healthy elderly 1 Subjects who are Thai male or female, aged ≥60 years. 2 Subjects whose BMI is 18-30 kg/m2 (inclusive). 3 Subjects who are healthy by medical history, physical examination and vital signs. 4 Subject whose screening visit laboratory values of blood tests including complete blood count, fasting blood sugar, blood urea nitrogen, serum creatinine, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, alpha-1-acid glycoprotein, total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, electrolytes, parathyroid hormone, Hepatitis Bs-antigen, anti-HIV are within the normal range or showing no clinically significant abnormalities as confirmed by the clinical investigator. 5 eGFR >80 ml/min/1.73 m2 as calculated by eGFR for Thai 6 Subjects are able to understand the requirements of the study and voluntarily sign and date an informed consent, approved by the Independent Ethic Committee (IEC)/ Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures. Group 3: the elderly with CKD 1 Subjects who are Thai male or female, aged ≥60 years. 2 Subjects whose BMI is 18-30 kg/m2 (incl
Exclusion criteria
Exclusion criteria: Exclusion criteria Group 1 healthy young subjects 1 Subjects who are with a history/evidence of allergy or hypersensitivity to dabigatran etexilate, midazolam, pitavastatin, rosuvastatin, atorvastatin and rifampicin. 2 Subjects who have a history of any illness that, in the opinion of the clinical investigator, might confound the result of study or pose an additional risk in administrating study drug to the subjects. This may include but not limited to: a history of relevant drug or food allergies; history or cardiovascular disease, gastrointestinal, central nervous system disease, renal and hepatic impairment; history or present of clinically significant illness; or history of mental illness that may affect compliance with study requirements. 3 Subjects who are with a history of heavy smoking (more than 10 cigarettes per day) or moderate smoking (less than 10 cigarettes per day) and cannot omit smoking a least one day before the study and until the completion of the study phase. 4 Subjects who are with a history of alcoholic (more than 2 years) or moderate drinker (more than 3 drinks per day – one is equal to one unit of alcohol: - one glass of mine, half pine of beer or one measure of spirit) or subject who are with a history of any drug abuse. 5 Subjects who receive of any medical prescription within 14 days before the first administration of the microdose cocktail, especially drug related to the study drug metabolizing enzyme 6 Female subjects who are pregnant or breast feeding. 7 Subjects who are participating in any investigational drug study or had been in any investigational drug study within 3 months prior to the screening visit. Group 2: the relatively healthy elderly 1 Subjects who are with a history/evidence of allergy or hypersensitivity to dabigatran etexilate, midazolam, pitavastatin, rosuvastatin, atorvastatin and rifampicin. 2 Subjects with hypertension and diabetes mellitus or and other major systemic disease. 3 Subjects with history of renal transplantation or liver transplantation 4 Subjects who are with a history of heavy smoking (more than 10 cigarettes per day) or moderate smoking (less than 10 cigarettes per day) and cannot omit smoking a least one day before the study and until the completion of the study phase. 5 Subjects who are with a history of alcoholic (more than 2 years) or moderate drinker (more than 3 drinks per day – one is equal to one unit of alcohol: - one glass of mine, half pine of beer or one measure of spirit) or subject who are with a history of any drug abuse. 6 Subjects who are participating in any investigational drug study or had been in any investigational drug study within 3 months prior to the screening visit. Group 3: the elderly with CKD 1 Subjects who are with a history/evidence of allergy or hypersensitivity to dabigatran etexilate, midazolam, pitavastatin, rosuvastatin, atorvastatin. 2 Subjects with history of renal transplantation, liver transplantation, hemodialysis and peritoneal dialysis. 3 Subjects who are with a history of heavy smoking (more than 10 cigarettes per day) or moderate smoking (less than 10 cigarettes per day) and cannot omit smoking a least one day before the study and until the completion of the study phase. 4 Subjects who are with a history of alcoholic (more than 2 years) or moderate drinker (more than 3 drinks per day – one is equal
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| the changes in PK determinants in elderly with and without CKD compared to healthy young subjects 2 years LC-MS | — |
Secondary
| Measure | Time frame |
|---|---|
| genetic variation of BCRP and OATP1B1 transporter among young healthy subject and eldery with or wi 2 years Real time PCR,The effect of transporter genetic variation to pharmacokinetics of microdose cocktail among 3 groups 2 years anova | — |
Countries
Thailand
Contacts
Public ContactPajaree Chariyavilaskul
Clinical pharmacokinetics and pharmacogenomics research unit
Outcome results
None listed