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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: PF-06842874; Drug: Placebo; Drug: Relative Bioavailability

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit
    • New Haven, Connecticut, United States, 06511
      • Pfizer New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PF-06842874/Placebo; Single dose administration of PF-06842874 or placebo	Drug: PF-06842874; Single dose administration of PF-06842874; Drug: Placebo; Single dose administration of placebo
EXPERIMENTAL: Relative Bioavailability; Determination of relative bioavailability of modified-release formulation relative to immediate-release formulation	Drug: Relative Bioavailability; Relative bioavailability assessment of modified-release formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)	Treatment-related AEs are any untoward medical occurrences attributed to study drug in a participant who received study drug.	Baseline up to 35 days after last dose of study medication
Number of Participants With Clinical Laboratory Abnormalities	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]).	Baseline up to 10 days after last dose of study medication
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	The following parameters will be analyzed for examination of vital signs: systolic blood pressure, diastolic blood pressure, and pulse rate.	0, 1, 2, 3, 5, 8, 12, 24, and 48 hours post-dose
Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings	Measurements of heart rate, PR interval, QT interval, QTc intervals, and QRS complex	0, 1, 2, 3, 5, 8, 12, 24, and 48 hours post-dose
Abnormal rhythms as observed continuous cardiac monitoring	Cardiac rhythms measured by continuous cardiac telemetry	0 to 8 hours post-dose
Number of Participants With Clinically-Significant Change From Baseline in Physical Examination Findings	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.	Baseline up to 10 days after last dose of study medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of PF-06842874	Maximum observed plasma concentration for immediate-release and modified-release formulations of PF-06842874	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 (AUClast) of PF-06842874	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	0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06842874	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).	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 (Tmax) of PF-06842874	Time to reach maximum observed plasma concentration for immediate-release and modified-release formulations of PF-06842874	0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose
Plasma Half-Life (t1/2) of PF-06842874	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.	0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 17, 2019
• Primary Completion (ACTUAL): July 26, 2021
• Study Completion (ACTUAL): July 26, 2021

Study Registration Dates

• First Submitted: October 10, 2019
• First Submitted That Met QC Criteria: October 10, 2019
• First Posted (ACTUAL): October 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 6, 2021
• Last Update Submitted That Met QC Criteria: December 3, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: relative bioavailability; CDK4/6; modified release; healthy participants; first in human; immediate release; PF-06842874; cyclin-dependent kinase 4; cyclin-dependent kinase 6
• Other Study ID Numbers: C4041001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No