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HealthyPhase 4NCT02743260

Drug Transporter Interaction Study PHENTRA_2015_KPUK

A Phase 4 study testing pitavastatin, Metformin and digoxin in people with Healthy, run by University of Cologne at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 85 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
pitavastatin, Metformin and digoxin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteGermany
Study dates
Apr 2016to Dec 2017
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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-

Who cannot join

  • 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)

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Department of Pharmacology I, University Hospital Cologne

    Cologne, North Rhine-Westphalia, 50931

Other trials in Germany

About this study

Official title: Single Centre in Vivo Cocktail Phenotyping Study on OATP1B1, OCT1/2, MATE1/2K, OAT1/3, and P-gp Drug Transporters in Healthy Volunteers

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.

Read the 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
Being tested
pitavastatin, Metformin, digoxin, Adefovir, sitagliptin
Keywords
phenotype, transporter, cocktail

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pitavastatinDrug

    Also called Livazo®

  • MetforminDrug

    Also called Metformin-CT®

  • digoxinDrug

    Also called Digacin®

  • AdefovirDrug

    Also called Hepsera®

  • sitagliptinDrug

    Also called Januvia®

Study groups in NCT02743260
Study groupRoleWhat they receive
pitavastatin (OATP1B1)Experimental2 mg pitavastatin single dose
Receives: Drug: pitavastatin
metformin (MATE1, MATE2K, OCT1, OCT2)Experimental500 mg metformin single dose
Receives: Drug: Metformin
digoxin (intestinal & renal P-glycoprotein)Experimental0.5 mg digoxin single dose
Receives: Drug: digoxin
adefovir dipivoxil (OAT1)Experimental10 mg adefovir dipivoxil single dose
Receives: Drug: Adefovir
sitagliptin (OAT3)Experimental100 mg sitagliptin single dose
Receives: Drug: sitagliptin
cocktail (all substances)Experimentalcombination of all individual drugs at respective single doses
Receives: Drug: pitavastatin; Drug: Metformin; Drug: digoxin; Drug: Adefovir; Drug: sitagliptin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    PK parameter

    Measured: 24 hours

  2. 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

    Measured: 24 hours

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

    PK parameter

    Measured: 24 hours

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

    PK parameter

    Measured: 24 hours

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

    PK parameter

    Measured: 24 hours

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

    PK parameter

    Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2016 (estimated)
  2. Study startApr 2016
  3. Primary completionDec 2017
  4. Study completionDec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02743260
Sponsor's protocol ID
PHENTRA_2015_KPUK
Status last verified
Sep 2019
First submitted
11 Apr 2016
Last updated
10 Sep 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32719417

  • 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.

    PubMed 31247117

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing pitavastatin, Metformin and digoxin in people with Healthy, run by University of Cologne at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

organic anionic transporter polypeptide 1B1 (OATP1B1): Clearance over bioavailability (CL/F) of pitavastatin (time frame: 24 hours). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02743260, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2019.

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