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Trial record 1 of 1 for:    NCT03796182
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Study of PF 04965842 Effect on MATE1/2K Activity in Healthy Participants

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ClinicalTrials.gov Identifier: NCT03796182
Recruitment Status : Completed
First Posted : January 8, 2019
Last Update Posted : May 24, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE January 4, 2019
First Posted Date  ICMJE January 8, 2019
Last Update Posted Date May 24, 2019
Actual Study Start Date  ICMJE January 10, 2019
Actual Primary Completion Date February 13, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 4, 2019)
Metformin CLr. [ Time Frame: 48 hrs after administration of Metformin with/without PF-04965842 ]
To estimate the effect of PF 04965842 on MATE1/2K activity via the pharmacokinetic assessment of a single, oral dose of metformin in healthy participants.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03796182 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2019)
  • Metformin AUCinf [ Time Frame: 48 hrs after administration of Metformin with/without PF-04965842 ]
    Area Under Concentration time curve is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
  • physical examinations and vital signs [ Time Frame: Baseline to Follow Up contact (28 - 35) days after the last dose of metformin ]
    Number of participants with potentially clinically important (PCI) physical examinations and vital signs is reported from Baseline to Follow Up contact (28 to 35) days after the last dose of metformin. Criteria for PCI change in vital signs: heart rate value of <40 beats per minute and value >150 beats per minute, systolic blood pressure (SBP) of <80 or >210 millimeter of mercury (mmHg), diastolic blood pressure (DBP) of <40 or >130 mmHg, temperature <32 or >40 degree centigrade,and criteria for PCI change in physical examination: >=10% increase or decrease of body weight in kilogram (kg).
  • Metformin Cmax [ Time Frame: 48 hrs after administration of Metformin with/without PF-04965842 ]
    Maximum Observed Plasma Concentration
  • Tmax [ Time Frame: 48 hrs after administration of metformin with/without PF-04965842 ]
    Time to Reach Maximum Observed Plasma Concentration (Tmax) of metformin with or without PF-04965842
  • AUClast [ Time Frame: 48 hrs after administration of metformin with/without PF-04965842 ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
  • CL/F [ Time Frame: 48 hours after administration of metformin with/without PF-04965842 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Vz/F [ Time Frame: 48 hrs after last dose of metformin with/without PF-04965842 ]
    Volume of distribution 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. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
  • t1/2 [ Time Frame: 48 hrs after the last dose of metformin with or without PF-04965842 ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) [ Time Frame: Baseline (Day 0) up to 35 days after last dose of study medication ]
    Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. 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.
  • Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 35 days after last dose of study treatment ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. 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.
  • Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities [ Time Frame: Baseline to 35 days after the last dose of study medication ]
    Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test [for all female participants]) and urine (urine pregnancy test [for all female participants]). Clinical significance of laboratory parameters is determined at the investigator's discretion.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of PF 04965842 Effect on MATE1/2K Activity in Healthy Participants
Official Title  ICMJE 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
Brief 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 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: Metformin
    Commercially available metformin (GLUCOPHAGE®) as 500 mg tablets.
    Other Name: Glucophage
  • Drug: PF-04965842
    PF 04965842 100 mg tablets
Study Arms  ICMJE
  • Experimental: Sequence 1
    Patients 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.
    Interventions:
    • Drug: Metformin
    • Drug: PF-04965842
  • Experimental: Sequence 2
    Patients 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.
    Interventions:
    • Drug: Metformin
    • Drug: PF-04965842
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 4, 2019)
12
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 12, 2019
Actual Primary Completion Date February 13, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03796182
Other Study ID Numbers  ICMJE B7451034
DDI ( Other Identifier: Alias Study Number )
2018-003683-31 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: 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.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP