A Study of Single Ascending Doses of PF-07258669 in Healthy Adult Participants

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: PF-07258669
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>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: PF-07258669<br>* PF-07258669 will be prepared as an oral solution and/or suspension given in escalating single doses to be determined<br>Drug: Placebo<br>* Matching placebo will be prepared as an oral solution and/or suspension given in each cohort<br>|
| Experimental: Cohort 2<br>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: PF-07258669<br>* PF-07258669 will be prepared as an oral solution and/or suspension given in escalating single doses to be determined<br>Drug: Placebo<br>* Matching placebo will be prepared as an oral solution and/or suspension given in each cohort<br>|
| Experimental: Cohort 3<br>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: PF-07258669<br>* PF-07258669 will be prepared as an oral solution and/or suspension given in escalating single doses to be determined<br>Drug: Placebo<br>* Matching placebo will be prepared as an oral solution and/or suspension given in each cohort<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) |  | Baseline up to 35 days after last dose of study intervention (approximately 11 weeks) | 
| Number of Participants With Clinical Laboratory Abnormalities |  | Baseline up to 10 days after last dose of study intervention (approximately 5 weeks) | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs |  | Baseline up to 10 days after last dose of study intervention (approximately 5 weeks) | 
| Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings |  | Baseline up to 10 days after last dose of study intervention (approximately 5 weeks) | 
| Number of Participants With Clinically-Significant Change From Baseline in Neurological Examination Findings |  | Baseline up to 10 days after last dose of study intervention (approximately 5 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of PF-07258669 |  | Hour 0, 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 post-dose in each period | 
| Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of PF-07258669 |  | Hour 0, 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 post-dose in each period | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07258669 |  | Hour 0, 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 post-dose in each period | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 |  | Hour 0, 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 post-dose in each period | 
| Plasma Half-Life (t1/2) of PF-07258669 |  | Hour 0, 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 post-dose in each period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PF-07258669, first in human, melanocortin-4 receptor, MC4R, healthy participants, safety, tolerability, pharmacokinetics