A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PF-06842874 in Healthy Participants

• ClinicalTrials.gov Identifier: NCT04124653
• Recruitment Status: Recruiting
• First Posted: October 11, 2019
• Last Update Posted: February 10, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: October 10, 2019
• First Posted Date: October 11, 2019
• Last Update Posted Date: February 10, 2021
• Actual Study Start Date: October 17, 2019
• Estimated Primary Completion Date: May 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 10, 2019)

• Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) [ Time Frame: Baseline up to 35 days after last dose of study medication ]
  Treatment-related AEs are any untoward medical occurrences attributed to study drug in a participant who received study drug.
• Number of Participants With Clinical Laboratory Abnormalities [ Time Frame: Baseline up to 10 days after last dose of study medication ]
  The following parameters will be analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, lactate dehydrogenase, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, phosphate, bicarbonate); clinical chemistry (glucose, creatine kinase); immunology (CRP); urinalysis (dipstick [urine specific gravity, decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin], microscopy [urine RBC, WBC, urate crystals, calcium, oxalate, miscellaneous [urine mucus and leucocytes]).
• Number of Participants With Clinically Significant Change From Baseline in Vital Signs [ Time Frame: 0, 1, 2, 3, 5, 8, 12, 24, and 48 hours post-dose ]
  The following parameters will be analyzed for examination of vital signs: systolic blood pressure, diastolic blood pressure, and pulse rate.
• Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings [ Time Frame: 0, 1, 2, 3, 5, 8, 12, 24, and 48 hours post-dose ]
  Measurements of heart rate, PR interval, QT interval, QTc intervals, and QRS complex
• Abnormal rhythms as observed continuous cardiac monitoring [ Time Frame: 0 to 8 hours post-dose ]
  Cardiac rhythms measured by continuous cardiac telemetry
• Number of Participants With Clinically-Significant Change From Baseline in Physical Examination Findings [ Time Frame: Baseline up to 10 days after last dose of study medication ]
  A complete physical examination includes, at a minimum, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. A limited physical examination includes, at a minimum, assessments of general appearance, the respiratory and cardiovascular systems, and participant-reported symptoms.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 8, 2021)

• Maximum Observed Plasma Concentration (Cmax) of PF-06842874 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Maximum observed plasma concentration for immediate-release and modified-release formulations of PF-06842874
• Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of PF-06842874 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration for immediate-release and modified-release formulations of PF-06842874
• Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06842874 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0-inf) for immediate-release and modified-release formulations of PF-06842874. It is obtained from AUC(0-t) plus AUC (t-inf).
• Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06842874 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Time to reach maximum observed plasma concentration for immediate-release and modified-release formulations of PF-06842874
• Plasma Half-Life (t1/2) of PF-06842874 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Plasma half-life is the time measured for the plasma concentration to decrease by one half for immediate-release and modified-release formulations of PF-06842874.

Original Secondary Outcome Measures (submitted: October 10, 2019)

• Maximum Observed Plasma Concentration (Cmax) of PF-06842874 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Maximum observed plasma concentration for immediate-release and modified-release formulations of PF-06842874
• Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of PF-06842874 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration for immediate-release and modified-release formulations of PF-06842874
• Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06842874 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0-inf) for immediate-release and modified-release formulations of PF-06842874. It is obtained from AUC(0-t) plus AUC (t-inf).
• Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06842874 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Time to reach maximum observed plasma concentration for immediate-release and modified-release formulations of PF-06842874
• Plasma Half-Life (t1/2) of PF-06842874 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Plasma half-life is the time measured for the plasma concentration to decrease by one half for immediate-release and modified-release formulations of PF-06842874.
• Ratio of Adjusted Geometric Means for Cmax [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Ratio of adjusted geometric means for Cmax for immediate-release and modified-release formulations of PF-06842874
• Ratio of Adjusted Geometric Means for AUClast [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Ratio of adjusted geometric means for AUClast for immediate-release and modified-release formulations of PF-06842874
• Ratio of Adjusted Geometric Means for AUCinf [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose ]
  Ratio of adjusted geometric means for AUCinf for immediate-release and modified-release formulations of PF-06842874

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PF-06842874 in Healthy Participants
• Official Title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, FIRST-IN-HUMAN STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF SINGLE ASCENDING ORAL DOSES OF PF-06842874 ADMINISTERED AS AN IMMEDIATE-RELEASE OR MODIFIED-RELEASE FORMULATION TO HEALTHY ADULT PARTICIPANTS AND AN OPEN-LABEL ASSESSMENT OF THE RELATIVE BIOAVAILABILITY OF A MODIFIED-RELEASE FORMULATION OF PF-06842874
• Brief Summary: This study will be the first time PF-06842874 is administered to humans. The purpose of Part A of the study is to investigate the safety, tolerability, and pharmacokinetics of PF-06842874 following administration of single oral doses as an immediate-release or modified-release formulation to healthy adult participants. Part B of this study will evaluate the relative bioavailability of a modified-release formulation of PF-06842874 for its potential use in future clinical studies. The effect of food on PF-06842874 pharmacokinetics may also be evaluated in this study.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

participant- and investigator-blind, sponsor-open

Primary Purpose: Basic Science

• Condition: Healthy Participants

Intervention

• Drug: PF-06842874
  Single dose administration of PF-06842874
• Drug: Placebo
  Single dose administration of placebo
• Drug: Relative Bioavailability
  Relative bioavailability assessment of modified-release formulation

Study Arms

• Experimental: PF-06842874/Placebo
  Single dose administration of PF-06842874 or placebo
  Interventions:

  • Drug: PF-06842874
  • Drug: Placebo
• Experimental: Relative Bioavailability
  Determination of relative bioavailability of modified-release formulation relative to immediate-release formulation
  Intervention: Drug: Relative Bioavailability

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 11, 2019): 98
• Original Estimated Enrollment (submitted: October 10, 2019): 36
• Estimated Study Completion Date: October 22, 2021
• Estimated Primary Completion Date: May 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Female participants of non-childbearing potential and male participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, clinical laboratory tests, and cardiac monitoring.
• 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.
• History of human immunodeficiency virus infection (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody.
• Participants with benign ethnic neutropenia or cyclic neutropenia.
• Other acute or chronic medical or psychiatric condition.
• 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.
• Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of investigational product used in this study (whichever is longer).
• A positive urine drug test.
• Screening supine blood pressure (BP) ≥140 mmHg (systolic) or ≥90 mmHg (diastolic), following at least 5 minutes of supine rest.
• Baseline 12-lead standard electrocardiogram (ECG) that demonstrates clinically relevant abnormalities.
• Participants with ANY of the following abnormalities in clinical laboratory tests at screening: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥1.25× upper limit of normal (ULN); total bilirubin level ≥1.5× ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ULN; hemoglobin ≤14 gm/dL (males) and ≤13 gm/dL (females); neutrophils <1500 cells/mm3.
• History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of screening.
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04124653
• Other Study ID Numbers: C4041001
• 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

• 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: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: February 2021