Drug Transporter Interaction Study PHENTRA_2015_KPUK
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT02743260
- Lead Sponsor
- University of Cologne
- Brief Summary
The objective of the present study is to contribute to establishing in vivo phenotyping procedures for organic anionic transporter polypeptide 1B1 (OATP1B1), organic cation transporters 1 and 2 (OCT1/2), multidrug and toxic compound extrusion transporters 1 and 2,kidney splice variant (MATE1/2K), organic anion transporters 1 and 3 (OAT1/3), and p-glycoprotein (P-gp) transporters via a cocktail approach. To this end, marker substrates for each of the respective transporters are administered as single doses in one period each and as a cocktail in one period to 24 healthy volunteers, and phenotyping metrics are derived from plasma and urine concentrations.
- Detailed Description
Blood sampling: - 0:15 h pre-dose, 0:15, 0:30, 0:45, 1:00, 1:20, 1:40, 2:00, 2:20, 2:40, 3:00, 3:30, 4:00, 5:00, 6:00, 8:00, 12:00, 16:00, 24:00 hours post-dose
Urine Sampling: Pre-dose, 0-4 hours, 4-8 hours, 8-12 hours, 12-16 hours, 16-24 hours
Drug analysis: by liquid chromatography - tandem mass spectrometry (LC-MS/MS)
Pharmacokinetic Characteristics: Evaluation is carried out using standard noncompartmental characteristics including: area under the plasma concentration vs. time curve truncated at time t (AUC0-t), area under the plasma concentration vs. time curve extrapolated to infinity (AUC0-∞), peak plasma concentration (Cmax), time of occurrence of Cmax (tmax), apparent elimination half-life (t½), clearance over bioavailability (CL/F), renal clearance (CLr) and renal secretion. The evaluation may be completed by compartmental population pharmacokinetic approaches.
Statistical evaluation: Pharmacokinetic characteristics are compared for cocktail administration vs. individual administration by standard average bioequivalence assessment.
Safety, tolerability: Adverse events, laboratory and clinical parameters and vital signs will be assessed.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
- Caucasian
- Body mass index (BMI) between and inclusive 18.5 and 30 kg/m2
- Willing and capable to confirm written consent prior to enrolment after ample information has been provided
- Normal findings in the medical history unless the principal investigator considers an abnormality to be clinically relevant.
- Considered to be healthy by the principal investigator on the basis of extensive pre-study screening-
Standard for healthy volunteers, including:
- Female subjects only: positive results in pregnancy test
- Female subjects only: lactating women
- Female subjects only: subjects who do not use or do not agree to use appropriate contraceptive methods during the study as defined in Note for Guidance on Non-Clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals (CHMP/ICH/286/95 modification)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description pitavastatin (OATP1B1) pitavastatin 2 mg pitavastatin single dose adefovir dipivoxil (OAT1) Adefovir 10 mg adefovir dipivoxil single dose cocktail (all substances) Metformin combination of all individual drugs at respective single doses metformin (MATE1, MATE2K, OCT1, OCT2) Metformin 500 mg metformin single dose digoxin (intestinal & renal P-glycoprotein) digoxin 0.5 mg digoxin single dose sitagliptin (OAT3) sitagliptin 100 mg sitagliptin single dose cocktail (all substances) pitavastatin combination of all individual drugs at respective single doses cocktail (all substances) digoxin combination of all individual drugs at respective single doses cocktail (all substances) Adefovir combination of all individual drugs at respective single doses cocktail (all substances) sitagliptin combination of all individual drugs at respective single doses
- Primary Outcome Measures
Name Time Method organic anionic transporter polypeptide 1B1 (OATP1B1): Clearance over bioavailability (CL/F) of pitavastatin 24 hours PK parameter
organic cation transporters 1 and 2 (OCT1/2), multidrug and toxic compound extrusion transporters 1 and 2,kidney splice variant (MATE1/2K): Renal clearance (CLr) of metformin 24 hours PK parameter
intestinal p-glycoprotein (P-gp): Peak Plasma Concentration (Cmax) of digoxin 24 hours PK parameter
renal p-glycoprotein (P-gp): Renal clearance (CLr) of digoxin: 24 hours PK parameter
organic anion transporter 1 (OAT1): Renal clearance (CLr) of adefovir 24 hours PK parameter
organic anion transporter 3 (OAT3): Renal clearance (CLr) of sitagliptin 24 hours PK parameter
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Department of Pharmacology I, University Hospital Cologne
🇩🇪Cologne, NRW, Germany