Clinical trial NCT06106009: A Study to Learn How Different Amounts of the Study Medicine Called PF-07976016 Are Tolerated and Act in The Body in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-10-30
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part A and B are randomized, double-blinded, sponsor-open, placebo-controlled studies to evaluate safety, tolerability, PK and PD of single and multiple escalating oral doses of PF-07976016 in healthy adult participants, respectively. Part A is a crossover while Part B is a parallel cohort study design. Part A of the study may also evaluate the safety, tolerability and PK in Japanese participants. Part C is an optional open-label, 4-period, fixed-sequence study to evaluate the effect of PF-07976016 on midazolam PK in healthy participants. Part D is an optional sponsor-open, randomized, double-blinded, placebo-controlled multiple dose study of PF-07976016 administered to participants with obesity.
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Number of Participants With Treatment Emergent Adverse Events Following Single Doses
timeFrame: Day 1 up to approximately Day 36
measure: Part A: Number of Participants With Clinical Laboratory Abnormalities Following Single Doses
timeFrame: Day 1 up to approximately Day 36
measure: Part A: Number of Participants With Clinically Significant Change in Baseline Vital Signs Following Single Doses
timeFrame: Day 1 up to approximately Day 36
measure: Part A: Number of Participants With Clinically Significant Change from Baseline in Electrocardiogram Findings Following Single Doses
timeFrame: Day 1 up to approximately Day 36
measure: Part B, Parts C and D, if conducted: Number of Participants With Treatment Emergent Adverse Events Following Multiple Doses
timeFrame: Day 1 up to approximately Day 49
measure: Part B, Parts C and D, if conducted: Number of Participants With Clinical Laboratory Abnormalities Following Multiple Doses
timeFrame: Day 1 up to approximately Day 49
measure: Part B, Parts C and D, if conducted: Number of Participants With Clinically Significant Change in Baseline Vital Signs Following Multiple Doses
timeFrame: Day 1 up to approximately Day 49
measure: Part B, Parts C and D, if conducted: Number of Participants With Clinically Significant Change from Baseline in Electrocardiogram Findings Following Multiple Doses
timeFrame: Day 1 up to approximately Day 49
Secondary outcomes:
measure: Part A: Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration
timeFrame: Day 1 up to Day 4
measure: Part A: Maximum Observed Plasma Concentration
timeFrame: Day 1 up to Day 4
measure: Part A: Time to Reach Maximum Observed Plasma Concentration
timeFrame: Day 1 up to Day 4
measure: Part A: Area Under the Curve From Time Zero to Extrapolated Infinite Time
timeFrame: Day 1 up to Day 4
measure: Part A: Plasma Half-Life
timeFrame: Day 1 up to Day 4
measure: Part B: Maximum Observed Plasma Concentration
timeFrame: Days 1, 7 and 14
measure: Part B: Time to Reach Maximum Observed Plasma Concentration
timeFrame: Days 1, 7 and 14
measure: Part B: Area Under the Curve From Time Zero to Time Tau
timeFrame: Days 1, 7 and 14
measure: Part B: Plasma Half-Life
timeFrame: Day 14
measure: Part B: Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau
timeFrame: Day 14
measure: Part B: Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau
timeFrame: Day 14
measure: Part B: Renal Clearance of Drug
timeFrame: Day 14
measure: Part C (if conducted): Maximum Observed Plasma Concentration of Midazolam
timeFrame: Day 1, Day 3 and Day 11
measure: Part C (if conducted): Area Under the Plasma Concentration-Time Curve from Time 0 to the Time of the Last Quantifiable Concentration of Midazolam
timeFrame: Day 1, Day 3 and Day 11
measure: Part C (if conducted): Area Under the Curve From Time Zero to Extrapolated Infinite Time of Midazolam
timeFrame: Day 1, Day 3 and Day 11
measure: Part D (if conducted): Maximum Observed Plasma Concentration of PF-07976016
timeFrame: Days 1 and 14
measure: Part D (if conducted): Time to Reach Maximum Observed Plasma Concentration of PF-07976016
timeFrame: Days 1 and 14
measure: Part D (if conducted): Area Under the Curve From Time Zero to Time Tau of PF-07976016
timeFrame: Days 1 and 14
measure: Part D (if conducted): Plasma Half-Life of PF-07976016
timeFrame: Day 14
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Pfizer Clinical Research Unit - New Haven
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: