Healthy
Conditions
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.
Interventions
DRUGPF-07976016
Oral solution, oral suspension or solid oral formulation(s)
DRUGPlacebo
Oral solution, oral suspension or solid oral formulation(s)
DRUGMidazolam
Midazolam oral solution
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Masking description
Parts A, B and D are double-blinded and sponsor-open while Part C is open-label.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 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 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 |
| 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 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 |
Countries
United States
Outcome results
None listed