Clinical trial NCT05677867: A Study to Compare Two Different Forms of PF-07081532 in Adults Who Are Overweight or Obese
Official title: A PHASE 1, OPEN-LABEL, 2-PERIOD, 2-SEQUENCE, CROSSOVER STUDY TO COMPARE THE SINGLE-DOSE PHARMACOKINETICS OF 2 DIFFERENT FORMULATIONS OF PF-07081532 ADMINISTERED ORALLY TO ADULT PARTICIPANTS WHO ARE OVERWEIGHT OR OBESE
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Overweight
Obesity
Keywords: PF-07081532
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-01-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: PF-07081532 80 mg will be provided in 2 different oral formulations (A and B). Formulation A will be administered as a PF-07081532 20 mg immediate release tablet and a 60 mg immediate release tablet. Formulation B will be administered as a PF-07081532 80 mg immediate release tablet. The overall design is a randomized, open-label, single dose, 2-period, 2-sequence, crossover study.
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to compare the amount of PF-07081532 in blood after taking two different forms of PF-07081532. This study is seeking participants who are at least 18 years of age and are overweight and/or obese. All study participants will receive a total of 2 single doses of this study medication in either form. Form A consists of a PF-07081532 20 mg immediate release tablet and a PF-07081532 60 mg immediate release tablet. Form B consists of a PF-07081532 80 mg immediate release tablet. Each single dose will be separated by a minimum of 6 days. The amount of PF-07081532 in the blood for 4 days after taking each single dose will be compared between the two different formulations of PF-07081532.

The total time that participants will take part in this study is about 70 days. The first visit is a screening visit to ensure that participants are appropriately qualified for the study. This will occur up to 28 days before the first single dose. Participants will be admitted into the clinic one day prior to the first single dose and will remain in the clinic for a total of 11 days. The study team will phone the participants 28 to 35 days after the last dose of study medication.


Eligibility criteria: Inclusion Criteria:

* Male and female participants must be at least 18 years of age, inclusive, at the time of signing the ICD
* Male and female participants who are healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and ECGs
* Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
* A total body weight \>50 kg (110 lb) and BMI of 25.0 to \<34.9 kg/m2, inclusive, at the screening visit
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and protocol

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)
* Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection)
* History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed
* Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2, or pancreatitis, or participants with suspected MTC per the investigator's judgement
* Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study
* 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
* In females, current use of hormone replacement therapy or oral/injectable contraceptives containing ethinyl estradiol
* Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives (whichever is longer) preceding the first dose of study intervention used in this study. Investigational products which are strong CYP3A inducers or time-dependent inhibitors are prohibited within 14 days plus 5 half-lives or 30 days (whichever is longer) prior to the dose of study intervention
* Known prior participation (ie, randomized and received at least 1 dose of investigational product) in a study involving PF-07081532 or known intolerance to a GLP-1R agonist
* A positive urine drug test
* Using a properly sized and calibrated BP cuff, screening supine BP ≥140 mm Hg (systolic) or 90 mm Hg (diastolic) following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility
* Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF \>450 ms, complete LBBB, signs of an acute or indeterminate- age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third- degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT interval is \>450 ms, this interval should be rate-corrected using the Fridericia method only and the resulting QTcF should be used for decision making and reporting. If QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding a participant
* 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:
* Aspartate aminotransferase or alanine aminotransferase level ≥1.25 × upper limit of normal (ULN);
* Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN;
* HbA1c ≥6.5%;
* Fasting blood glucose ≥126 mg/dL (7 mmol/L);
* Calcitonin \> ULN;
* eGFR \<60 mL/min/1.73 m2 as calculated by the CKD-EPI equation.

Primary outcomes:
measure: Pharmacokinetics Parameter - Area Under the Concentration-Time Curve to Infinity (AUCinf) of PF-07081532
timeFrame: Pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours post dose on Day 1 of Period 1 and Period 2
measure: Pharmacokinetics Parameter - Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532
timeFrame: Pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours post dose on Day 1 of Period 1 and Period 2
measure: Pharmacokinetics Parameter - Maximum Observed Concentration (Cmax) of PF-07081532
timeFrame: Pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours post dose of Day 1 Period 1 and Period 2.
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All-Causality and Treatment-Related)
timeFrame: From the first dose up to 28 to 35 days after administration of the final dose of study intervention (maximum of 51 days)
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline (Day 1) up to Period 2 Day 5
measure: Number of Participants Meeting Pre-Specified Criteria of Vital Signs
timeFrame: Baseline (Day 1) up to Period 2 Day 5
measure: Number of Participants Meeting Pre-Specified Criteria of Electrocardiogram (ECGs)
timeFrame: Baseline (Day 1) up to Period 2 Day 5
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: