A Study of Single Ascending Doses of PF-07258669 in Healthy Adult 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-07258669 ADMINISTERED TO HEALTHY ADULT PARTICIPANTS

This study will be the first time PF-07258669 is administered to humans. The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of PF-07258669 following administration of single oral doses to healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Placebo; Drug: PF-07258669

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • South Miami, Florida, United States, 33143
      • QPS-MRA, LLC-Main Office

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Female participants of non-child bearing potential and male participants and who are overtly healthy as determined by medical evaluation including medical history, physical examination, neurological examination, laboratory tests, and cardiac monitoring.
• Participants who are willing to avoid direct sunlight exposure or any high intensity ultraviolet light exposure from admission to the follow-up contact and to apply sunscreen/lotion with a high sun protection factor, as appropriate.
• BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing), as well as presence of lipid panel abnormalities (eg, hypercholesterolemia, hypertriglyceridemia).
• Evidence of history of orthostatic hypotension or symptomatic bradycardia.
• 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 study intervention.
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
• Current findings or documented past history of blood pressure values <90 mmHg systolic or <50 mmHg diastolic.
• Any lipid panel parameter (ie, total cholesterol, triglycerides, HDL, and/or LDL) ≥1.25× ULN.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Single dose administration of PF-07258669 and placebo; Within a cohort, participants will receive 3 doses of PF-07258669 and 1 dose of placebo.	Drug: Placebo; Matching placebo will be prepared as an oral solution and/or suspension given in each cohort; Drug: PF-07258669; PF-07258669 will be prepared as an oral solution and/or suspension given in escalating single doses to be determined
Experimental: Cohort 2; Single dose administration of PF-07258669 and placebo; Within a cohort, participants will receive 3 doses of PF-07258669 and 1 dose of placebo.	Drug: Placebo; Matching placebo will be prepared as an oral solution and/or suspension given in each cohort; Drug: PF-07258669; PF-07258669 will be prepared as an oral solution and/or suspension given in escalating single doses to be determined
Experimental: Cohort 3; Single dose administration of PF-07258669 and placebo; Within a cohort, participants will receive 3 doses of PF-07258669 and 1 dose of placebo.	Drug: Placebo; Matching placebo will be prepared as an oral solution and/or suspension given in each cohort; Drug: PF-07258669; PF-07258669 will be prepared as an oral solution and/or suspension given in escalating single doses to be determined

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment. AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE.	From first dose of study intervention (Day 1) to telephone Follow Up (28-35 days after lase dose of study intervention) (approximately up to 20 weeks)
Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality)	Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion.	From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks)
Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria	Abnormality in change from BL in vital signs included: standing diastolic blood pressure (BP) increase and decrease from BL of >=20mmHg, standing systolic BP increase and decrease from BL of >=30mmHg, supine diastolic BP increase and decrease from BL of >=20mmHg, supine systolic BP increase and decrease from BL of >=30mmHg.	From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks)
Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria	ECG assessments inlcuded PR, QT, QTcF intervals and QRS complex. ECG abnormalities in change from BL included: PR interval BL >200msec and max >=25% increase from BL, or BL <=200msec and max >=50% increase from BL, QRS interval percent change from BL >=50%, QTcF change from BL >=30 and <=60msec, or change from BL >60msec.	From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks)
Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings	The neurological exam consisted of assessment of higher cortical function, the cranial nerves, motor function, deep tendon reflexes, sensory exam, and coordination and gait, to the extent needed to assess the participant for any potential changes in neurological status, as determined by the investigator (or designee).	From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of PF-07258669	Cmax is the maximum observed plasma concentration.	At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4
Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669	AUClast is the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.	At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4
Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669	AUCinf is the area under the plasma concentration time profile from time 0 extrapolated to infinite time.	At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4
Time for Cmax (Tmax) of PF-07258669	Tmax is the time for Cmax.	At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4
Terminal Half-life (t1/2) of PF-07258669	t1/2 is the terminal half-life.	At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, 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): March 16, 2021
• Primary Completion (Actual): August 25, 2021
• Study Completion (Actual): August 25, 2021

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 9, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: tolerability; safety; pharmacokinetics; MC4R; healthy participants; PF-07258669; first in human; melanocortin-4 receptor
• Other Study ID Numbers: C4541001; 2020-004280-42 (EudraCT Number)

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