Drug Transporter Interaction Study PHENTRA_2015_KPUK

NCT ID: NCT02743260

Last Updated: 2019-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2017-12-31

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

pitavastatin (OATP1B1)

2 mg pitavastatin single dose

Group Type: EXPERIMENTAL

pitavastatin

Intervention Type: DRUG

metformin (MATE1, MATE2K, OCT1, OCT2)

500 mg metformin single dose

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

digoxin (intestinal & renal P-glycoprotein)

0.5 mg digoxin single dose

Group Type: EXPERIMENTAL

digoxin

Intervention Type: DRUG

adefovir dipivoxil (OAT1)

10 mg adefovir dipivoxil single dose

Group Type: EXPERIMENTAL

Adefovir

Intervention Type: DRUG

sitagliptin (OAT3)

100 mg sitagliptin single dose

Group Type: EXPERIMENTAL

sitagliptin

Intervention Type: DRUG

cocktail (all substances)

combination of all individual drugs at respective single doses

Group Type: EXPERIMENTAL

pitavastatin

Intervention Type: DRUG

Metformin

Intervention Type: DRUG

digoxin

Intervention Type: DRUG

Adefovir

Intervention Type: DRUG

sitagliptin

Intervention Type: DRUG

Interventions

pitavastatin

Intervention Type: DRUG

Metformin

Intervention Type: DRUG

digoxin

Intervention Type: DRUG

Adefovir

Intervention Type: DRUG

sitagliptin

Intervention Type: DRUG

Other Intervention Names

Livazo®; Metformin-CT®; Digacin®; Hepsera®; Januvia®

Eligibility Criteria

Inclusion Criteria

• 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-

Exclusion Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Umm Al-Qura University

OTHER

Sponsor Role: collaborator

Institute for Biomedical and Pharmaceutical Research (IBMP), Nürnberg-Heroldsberg, Germany

UNKNOWN

Sponsor Role: collaborator

University of Cologne

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Uwe Fuhr

Acting Director, Department of Pharmacology I

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Uwe Fuhr, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Department of Pharmacology I, University Hospital Cologne Cologne, NRW, Germany, 50931

Locations

Department of Pharmacology I, University Hospital Cologne

Cologne, North Rhine-Westphalia, Germany

Countries

Germany

References

Hsin CH, Stoffel MS, Gazzaz M, Schaeffeler E, Schwab M, Fuhr U, Taubert M. Combinations of common SNPs of the transporter gene ABCB1 influence apparent bioavailability, but not renal elimination of oral digoxin. Sci Rep. 2020 Jul 27;10(1):12457. doi: 10.1038/s41598-020-69326-y.

Reference Type: DERIVED

PMID: 32719417 (View on PubMed)

Trueck C, Hsin CH, Scherf-Clavel O, Schaeffeler E, Lenssen R, Gazzaz M, Gersie M, Taubert M, Quasdorff M, Schwab M, Kinzig M, Sorgel F, Stoffel MS, Fuhr U. A Clinical Drug-Drug Interaction Study Assessing a Novel Drug Transporter Phenotyping Cocktail With Adefovir, Sitagliptin, Metformin, Pitavastatin, and Digoxin. Clin Pharmacol Ther. 2019 Dec;106(6):1398-1407. doi: 10.1002/cpt.1564. Epub 2019 Aug 12.

Reference Type: DERIVED

PMID: 31247117 (View on PubMed)

Other Identifiers

PHENTRA_2015_KPUK

Identifier Type: -

Identifier Source: org_study_id