Drug Transporter Interaction Study PHENTRA_2015_KPUK

NCT02743260 | Completed Phase 4

• 1 other identifier: PHENTRA_2015_KPUK
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

phenotype; transporter; cocktail

Outcome Measures

Primary Outcomes (6)

• organic anionic transporter polypeptide 1B1 (OATP1B1): Clearance over bioavailability (CL/F) of pitavastatin

  PK parameter

  24 hours

• 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

  PK parameter

  24 hours

• intestinal p-glycoprotein (P-gp): Peak Plasma Concentration (Cmax) of digoxin

  PK parameter

  24 hours

• renal p-glycoprotein (P-gp): Renal clearance (CLr) of digoxin:

  PK parameter

  24 hours

• organic anion transporter 1 (OAT1): Renal clearance (CLr) of adefovir

  PK parameter

  24 hours

• organic anion transporter 3 (OAT3): Renal clearance (CLr) of sitagliptin

  PK parameter

  24 hours

Study Arms (6)

pitavastatin (OATP1B1)

EXPERIMENTAL

2 mg pitavastatin single dose

Drug: pitavastatin

metformin (MATE1, MATE2K, OCT1, OCT2)

EXPERIMENTAL

500 mg metformin single dose

Drug: Metformin

digoxin (intestinal & renal P-glycoprotein)

EXPERIMENTAL

0.5 mg digoxin single dose

Drug: digoxin

adefovir dipivoxil (OAT1)

EXPERIMENTAL

10 mg adefovir dipivoxil single dose

Drug: Adefovir

sitagliptin (OAT3)

EXPERIMENTAL

100 mg sitagliptin single dose

Drug: sitagliptin

cocktail (all substances)

EXPERIMENTAL

combination of all individual drugs at respective single doses

Drug: pitavastatin; Drug: Metformin; Drug: digoxin; Drug: Adefovir; Drug: sitagliptin

Interventions

pitavastatin DRUG

Also known as: Livazo®

cocktail (all substances); pitavastatin (OATP1B1)

Metformin DRUG

Also known as: Metformin-CT®

cocktail (all substances); metformin (MATE1, MATE2K, OCT1, OCT2)

digoxin DRUG

Also known as: Digacin®

cocktail (all substances); digoxin (intestinal & renal P-glycoprotein)

Adefovir DRUG

Also known as: Hepsera®

adefovir dipivoxil (OAT1); cocktail (all substances)

sitagliptin DRUG

Also known as: Januvia®

cocktail (all substances); sitagliptin (OAT3)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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-

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Cologne: lead
• Umm Al-Qura University: collaborator
• Institute for Biomedical and Pharmaceutical Research (IBMP), Nürnberg-Heroldsberg, Germany: collaborator

Study Sites (1)

Department of Pharmacology I, University Hospital Cologne

Cologne, North Rhine-Westphalia, 50931, Germany

Location

Related Publications (2)

• 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.

  PMID: 32719417 DERIVED

• 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.

  PMID: 31247117 DERIVED

MeSH Terms

Interventions

pitavastatin; Metformin; Digoxin; adefovir; adefovir dipivoxil; Sitagliptin Phosphate

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Uwe Fuhr, Prof. Dr.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Acting Director, Department of Pharmacology I

Study Record Dates

• First Submitted: April 11, 2016
• First Posted: April 19, 2016
• Study Start: April 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: September 10, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)