A Study to Learn How Different Amounts of the Study Medicine Called PF-07976016 Are Tolerated and Act in The Body in Healthy Adults

A Multi-Part, Phase 1 Study With Randomized, Double-Blind, Sponsor-Open, Placebo-Controlled, Single- And Multiple-Dose Escalation To Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-07976016 In Healthy Adult Participants

The purpose of this clinical trial is to learn if the study medicine (called PF-07976016) is safe and how it goes in and out of the body in healthy people. The study may also explore if PF-07976016 has the potential to interact with another medicine called midazolam. In addition, the study may explore how PF-07976016 goes into the body of people who have obesity.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Midazolam; Drug: PF-07976016; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Male and female participants of non-childbearing potential aged 18 to 65 years, inclusive, at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
2. A total body weight >50 kg (110 lb).
3. Parts A, B and C only: BMI of 20-33 kg/m2.
4. Part D only: BMI of 30-40 kg/m2 and may have well controlled hyperlipidemia or hypertension.

Key Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, skin or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
2. Any condition possibly affecting drug absorption.
3. Previous administration with an investigational product (drug or vaccine) 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). Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study.
4. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
5. Renal impairment as defined by an estimated glomerular filtration rate of <75 mL/min/1.73 m².

6. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:

   • alanine aminotransferase, aspartate aminotransferase, or bilirubin ≥1.05 × upper limit of normal;
   • fasting plasma glucose > 126 mg/dL;
   • HbA1c ≥6.0% (Parts A,B and C); HbA1c ≥6.5% (Part D);
   • hematuria as defined by ≥1+ heme on urine dipstick;
   • albuminuria as defined by urine albumin/creatinine ratio >30 mg/g.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Cohort 1; Single dose administration of PF-07976016 and placebo. Participants will receive up to 4 dose levels of PF-07976016 or matching placebo.	Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s); Drug: Placebo; Oral solution, oral suspension or solid oral formulation(s)
Experimental: Part A Cohort 2; Single dose administration of PF-07976016 and placebo. Participants will receive up to 4 dose levels of PF-07976016 or matching placebo.	Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s); Drug: Placebo; Oral solution, oral suspension or solid oral formulation(s)
Experimental: Part A Optional Cohort 3; Single dose administration of PF-07976016 and placebo. Participants will receive up to 2 dose levels of PF-07976016 or matching placebo.	Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s); Drug: Placebo; Oral solution, oral suspension or solid oral formulation(s)
Experimental: Part A Optional Cohort 4; Single dose administration of PF-07976016 and placebo. Participants will receive up to 4 dose levels of PF-07976016 or matching placebo.	Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s); Drug: Placebo; Oral solution, oral suspension or solid oral formulation(s)
Experimental: Part B Cohort 5; Multiple dose administration of PF-07976016 or matching placebo.	Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s); Drug: Placebo; Oral solution, oral suspension or solid oral formulation(s)
Experimental: Part B Cohort 6; Multiple dose administration of PF-07976016 or matching placebo.	Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s); Drug: Placebo; Oral solution, oral suspension or solid oral formulation(s)
Experimental: Part B Cohort 7; Multiple dose administration of PF-07976016 or matching placebo.	Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s); Drug: Placebo; Oral solution, oral suspension or solid oral formulation(s)
Experimental: Part B Cohort 8; Multiple dose administration of PF-07976016 or matching placebo.	Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s); Drug: Placebo; Oral solution, oral suspension or solid oral formulation(s)
Experimental: Part B Cohort 9; Multiple dose administration of PF-07976016 or matching placebo.	Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s); Drug: Placebo; Oral solution, oral suspension or solid oral formulation(s)
Experimental: Part B Optional Cohort 10; Multiple dose administration of PF-07976016 or matching placebo.	Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s); Drug: Placebo; Oral solution, oral suspension or solid oral formulation(s)
Experimental: Part C Optional Cohort 11; Single dose midazolam administered alone or in combination with multiple doses of PF-07976016.	Drug: Midazolam; Midazolam oral solution; Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s)
Experimental: Part C Optional Cohort 12; Single dose midazolam administered alone or in combination with multiple doses of PF-07976016.	Drug: Midazolam; Midazolam oral solution; Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s)
Experimental: Part D Optional Cohort 13; Multiple dose administration of PF-07976016 or matching placebo.	Drug: PF-07976016; Oral solution, oral suspension or solid oral formulation(s); Drug: Placebo; Oral solution, oral suspension or solid oral formulation(s)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part A: Number of Participants With Treatment Emergent Adverse Events Following Single Doses	Day 1 up to approximately Day 36
Part A: Number of Participants With Clinical Laboratory Abnormalities Following Single Doses	Day 1 up to approximately Day 36
Part A: Number of Participants With Clinically Significant Change in Baseline Vital Signs Following Single Doses	Day 1 up to approximately Day 36
Part A: Number of Participants With Clinically Significant Change from Baseline in Electrocardiogram Findings Following Single Doses	Day 1 up to approximately Day 36
Part B, Parts C and D, if conducted: Number of Participants With Treatment Emergent Adverse Events Following Multiple Doses	Day 1 up to approximately Day 49
Part B, Parts C and D, if conducted: Number of Participants With Clinical Laboratory Abnormalities Following Multiple Doses	Day 1 up to approximately Day 49
Part B, Parts C and D, if conducted: Number of Participants With Clinically Significant Change in Baseline Vital Signs Following Multiple Doses	Day 1 up to approximately Day 49
Part B, Parts C and D, if conducted: Number of Participants With Clinically Significant Change from Baseline in Electrocardiogram Findings Following Multiple Doses	Day 1 up to approximately Day 49

Secondary Outcome Measures

Outcome Measure	Time Frame
Part A: Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration	Day 1 up to Day 4
Part A: Maximum Observed Plasma Concentration	Day 1 up to Day 4
Part A: Time to Reach Maximum Observed Plasma Concentration	Day 1 up to Day 4
Part A: Area Under the Curve From Time Zero to Extrapolated Infinite Time	Day 1 up to Day 4
Part A: Plasma Half-Life	Day 1 up to Day 4
Part B: Maximum Observed Plasma Concentration	Days 1, 7 and 14
Part B: Time to Reach Maximum Observed Plasma Concentration	Days 1, 7 and 14
Part B: Area Under the Curve From Time Zero to Time Tau	Days 1, 7 and 14
Part B: Plasma Half-Life	Day 14
Part B: Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau	Day 14
Part B: Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau	Day 14
Part B: Renal Clearance of Drug	Day 14
Part C (if conducted): Maximum Observed Plasma Concentration of Midazolam	Day 1, Day 3 and Day 11
Part C (if conducted): Area Under the Plasma Concentration-Time Curve from Time 0 to the Time of the Last Quantifiable Concentration of Midazolam	Day 1, Day 3 and Day 11
Part C (if conducted): Area Under the Curve From Time Zero to Extrapolated Infinite Time of Midazolam	Day 1, Day 3 and Day 11
Part D (if conducted): Maximum Observed Plasma Concentration of PF-07976016	Days 1 and 14
Part D (if conducted): Time to Reach Maximum Observed Plasma Concentration of PF-07976016	Days 1 and 14
Part D (if conducted): Area Under the Curve From Time Zero to Time Tau of PF-07976016	Days 1 and 14
Part D (if conducted): Plasma Half-Life of PF-07976016	Day 14

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): October 27, 2023
• Primary Completion (Actual): August 19, 2024
• Study Completion (Actual): August 19, 2024

Study Registration Dates

• First Submitted: October 24, 2023
• First Submitted That Met QC Criteria: October 24, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Actual): September 23, 2024
• Last Update Submitted That Met QC Criteria: September 19, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: C5541001

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