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HealthyPhase 1NCT03796182

Study of PF 04965842 Effect on MATE1/2K Activity in Healthy Participants

A Phase 1 study testing Metformin and PF-04965842 in people with Healthy, run by Pfizer at 1 site in Belgium.

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

This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF-04965842 on metformin (a probe for MATE1/2K activity) PK in healthy adult participants. The effect of PF-04965842 on N1-methylnicotinamide (NMN; an endogenous biomarker for MATE1/2K) PK and its correlation to the effect on metformin… Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Metformin and PF-04965842
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteBelgium
Study dates
10 Jan 2019to 12 Mar 2019
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Male and female participants who are overtly healthy as determined by medical evaluation including a detailed medical history, complete physical examination, laboratory tests, and cardiovascular tests.
  • Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
  • Female participants who are of child bearing potential must not be intending to become pregnant, currently pregnant, or lactating.
  • Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
  • Capable of giving signed informed consent.

Who cannot join

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
  • Any condition possibly affecting drug absorption (eg, gastrectomy).
  • History of human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus infection; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C virus antibody (HCVAb).
  • Other acute or chronic medical or psychiatric condition including recent (within the past year).
  • Evidence or history of clinically significant dermatological condition (eg, atopic dermatitis or psoriasis) or visible rash present during physical examination.
  • Clinically relevant history of lactic acidosis.
Show all 14Show fewer
  • Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of investigational product.
  • A positive urine drug test.
  • Selected laboratory abnormalities.
  • History of regular alcohol consumption exceeding 14 drinks/week for female participants or 21 drinks/week for male participants (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months before screening.
  • Known relevant history of elevated liver function tests (LFTs).
  • History of tuberculosis (TB) (active or latent)
  • Any history of chronic infections, any history of recurrent infections, any history of latent infections, or any acute infection within 2 weeks of baseline.
  • History of disseminated herpes zoster, or disseminated herpes simplex, or recurrent localized dermatomal herpes zoster.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • Pfizer Clinical Research Unit

    Brussels, B-1070

Other trials in Belgium

About this study

Official title: A PHASE 1, RANDOMIZED, 2-WAY CROSSOVER, OPEN LABEL STUDY TO ESTIMATE THE EFFECT OF PF-04965842 ON MATE1/2K ACTIVITY, USING METFORMIN AS A PROBE, IN HEALTHY PARTICIPANTS

This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF-04965842 on metformin (a probe for MATE1/2K activity) PK in healthy adult participants. The effect of PF-04965842 on N1-methylnicotinamide (NMN; an endogenous biomarker for MATE1/2K) PK and its correlation to the effect on metformin PK will also be assessed. Participants will be randomized to 1 of 2 treatment sequences as described below. A total of 12 healthy male and/or female participants will be enrolled in the study so that 6 participants will be enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods.

Read the detailed description

This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF-04965842 on metformin (a probe for MATE1/2K activity) PK in healthy adult participants. The effect of PF-04965842 on N1-methylnicotinamide (NMN; an endogenous biomarker for MATE1/2K) PK and its correlation to the effect on metformin PK will also be assessed. Participants will be randomized to 1 of 2 treatment sequences as described below. A total of 12 healthy male and/or female participants will be enrolled in the study so that 6 participants will be enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods. Participants who discontinue from the study may be replaced at the sponsor's discretion. The replacement participant will receive the same treatment sequence as the participant who discontinued.

Participants will be screened within 28 days of the first dose of investigational product. Participants will report to the clinical research unit (CRU) the day prior to Day 1 (ie Day -1) dosing in Period 1 for both treatment sequences. In both sequences, participants will remain in the CRU for a total of 8 days and 7 nights (including Period 1 and Period 2). There will be a minimum 4 day washout period between metformin dosing events. NMN and metformin PK will be assessed in plasma and urine over 24 and 48 hours, respectively.

Conditions
Healthy
Being tested
Metformin, PF-04965842
Keywords
Phase 1, Metformin, Atopic dermatitis
Medical subject headings
Dermatitis, Atopic

What participants receive

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

  • MetforminDrug

    Also called Glucophage

    Commercially available metformin (GLUCOPHAGE®) as 500 mg tablets.

  • PF-04965842Drug

    PF 04965842 100 mg tablets

Study groups in NCT03796182
Study groupRoleWhat they receive
Sequence 1ExperimentalPatients in sequence 1 will received treatment A (metformin) in Period 1 then complete at least 4 days of washout and continue to period 2 where treatment B (PF-04965842 + metformin) will be administered.
Receives: Drug: Metformin; Drug: PF-04965842
Sequence 2ExperimentalPatients in Sequence 2 will start treatment B (PF-04965842 + metformin) then go through a washout period of at least 4 days and continue to Period 2 where treatment A (metformin) will be administered.
Receives: Drug: Metformin; Drug: PF-04965842

What is being measured

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

  1. Renal Clearance (CLr) of Metformin

    CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).

    Measured: For both Period 1 and Period 2 at intervals of 0-12, 12-24, 24-36, and 36-48 hours post metformin dose

Secondary outcomes (13)

  1. Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Metformin

    AUCinf is a measure of the serum concentration of the drug over time. It was used to characterize drug absorption.

    Measured: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2

  2. Maximum Plasma Concentration (Cmax) of Metformin

    Cmax is maximum observed plasma concentration.

    Measured: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2

  3. Time for Cmax (Tmax) of Metformin

    Tmax of metformin administrated with or without PF-04965842.

    Measured: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2

  4. Area Under the Plasma Concentration Time Profile From Time 0 to the Time of Last Quantifiable Concentration (AUClast) of Metformin

    AUClast of metformin administrated with or without PF-04965842.

    Measured: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2

  5. Apparent Clearance (CL/F) of Metformin

    CL/F is a quantitative measure of the rate at which drug was removed from the blood.

    Measured: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2

  6. Apparent Volume of Distribution (Vz/F) of Metformin

    Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

    Measured: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2

  7. Terminal Half-life (t1/2) of Metformin

    t1/2 is the time measured for the plasma concentration to decrease by one half.

    Measured: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2

  8. Cumulative Amount of Drug Recovered Unchanged in Urine From 0 to 48 Hours (Ae) of Metformin

    Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020), where 1.020 g/mL is the approximate specific gravity of urine.

    Measured: For both Period 1 and Period 2 at intervals of 0-12, 12-24, 24-36, and 36-48 hours post metformin dose

  9. Percent of Dose Recovered Unchanged in Urine From 0 to 24 Hours (Ae%) of Metformin

    Ae% is percent of dose recovered unchanged in urine from 0 to 24 hours post-dose of metformin.

    Measured: For both Period 1 and Period 2 at intervals of 0-12 and 12-24 hours post metformin dose

  10. Number of Participants With Laboratory Abnormalities

    Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocytes, ery. mean corpuscular volume, ery. mean corpuscular hemoglobin, ery. mean corpuscular HGB concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time, prothrombin intl. normalized ratio, large unstained cells/leukocytes and large unstained cells), clinical chemistry (bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, urea, creatinine, urate, sodium, potassium, chloride, calcium, bicarbonate, urobilinogen and glucose -FASTING), urinalysis (specific gravity, pH, urine glucose, ketones, urine protein, urine hemoglobin, urine bilirubin, nitrite and leukocytes). Clinical significance of laboratory parameters is determined at the investigator's discretion.

    Measured: Screening (within 28 days prior to Day 1) to Day 7

  11. Number of Participants With Categorical Vital Signs Meeting Pre-defined Criteria

    Criteria for change in vital signs: pulse rate value less than (<) 40 beats per minute (bpm) or value over than (>) 120 bpm, systolic blood pressure (SBP) value < 90 millimeter of mercury (mmHg) or change from baseline (Chg) equal to or over than (≥) 30 mmHg increase or ≥ Chg 30 mmHg decrease, diastolic blood pressure (DBP) value < 50 mmHg or Chg ≥ 20 mmHg increase or Chg ≥ 20 mmHg decrease.

    Measured: Screening (within 28 days prior to Day 1) to Day 7

  12. Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)

    AEs with all causalities were any untoward medical occurrences in a study subject administered a product or medical device which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

    Measured: Day 1 up to Day 40 (35 days after the last dose of metformin)

  13. Percentage of Participants With Treatment-Emergent AEs and SAEs (All Causalities and Treatment-related)

    AEs with all causalities were any untoward medical occurrences in a study subject administered a product or medical device which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

    Measured: Day 1 up to Day 40 (35 days after the last dose of metformin)

Timeline

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

  1. First posted8 Jan 2019
  2. Study start10 Jan 2019
  3. Primary completion13 Feb 2019
  4. Study completion12 Mar 2019

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF 04965842 on metformin PK in healthy adult participants. The effect of PF 04965842 on N1 methylnicotinamide (NMN) PK and its correlation to the effect on metformin PK will also be assessed. A total of approximately 12 healthy male and/or female participants will be enrolled in the study so that approximately 6 participants will be enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods. Participants who discontinue from the study may be replaced at the sponsor's discretion. The replacement participant will receive the same treatment sequence as the participant who discontinued. Participants will be screened within 28 days of the first dose of investigational product. Participants will report to the clinical research unit (CRU) the day prior to Day 1 (ie Day -1) dosing in Period 1 for both treatment sequences. In both sequences, participants will remain in the CRU for
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03796182
Sponsor's protocol ID
B7451034
Other IDs
DDI, 2018-003683-31, 2018
Status last verified
Jan 2020
First submitted
4 Jan 2019
Last updated
5 Feb 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Publications

  • Vourvahis M, Byon W, Chang C, Le V, Diehl A, Graham D, Tripathy S, Raha N, Luo L, Mathialagan S, Dowty M, Rodrigues AD, Malhotra B. Evaluation of the Effect of Abrocitinib on Drug Transporters by Integrated Use of Probe Drugs and Endogenous Biomarkers. Clin Pharmacol Ther. 2022 Sep;112(3):665-675. doi: 10.1002/cpt.2594. Epub 2022 May 9.

    PubMed 35344588

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Metformin and PF-04965842 in people with Healthy, run by Pfizer at 1 site in Belgium.

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 14 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 5 Feb 2020. 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 Belgium. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Renal Clearance (CLr) of Metformin (time frame: For both Period 1 and Period 2 at intervals of 0-12, 12-24, 24-36, and 36-48 hours post metformin dose). 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 NCT03796182, which also lists 1 linked publication.

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 5 Feb 2020.

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