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

NCT04124653 | Completed Phase 1 FDA Drug

• 1 other identifier: C4041001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

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.

Conditions

Healthy Participants

Keywords

PF-06842874; first in human; cyclin-dependent kinase 4; cyclin-dependent kinase 6; CDK4/6; healthy participants; immediate release; modified release; relative bioavailability

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (5)

• Maximum Observed Plasma Concentration (Cmax) 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

  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

  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

  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

  0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose

Study Arms (2)

PF-06842874/Placebo

EXPERIMENTAL

Single dose administration of PF-06842874 or placebo

Drug: PF-06842874; Drug: Placebo

Relative Bioavailability

EXPERIMENTAL

Determination of relative bioavailability of modified-release formulation relative to immediate-release formulation

Drug: Relative Bioavailability

Interventions

PF-06842874 DRUG

Single dose administration of PF-06842874

PF-06842874/Placebo

Placebo DRUG

Single dose administration of placebo

PF-06842874/Placebo

Relative Bioavailability DRUG

Relative bioavailability assessment of modified-release formulation

Relative Bioavailability

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Links

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

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: participant- and investigator-blind, sponsor-open
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2019
• First Posted: October 11, 2019
• Study Start: October 17, 2019
• Primary Completion: July 26, 2021
• Study Completion: July 26, 2021
• Last Updated: December 6, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)