Efficacy and safety of obese adults

The effect of various doses of PF-06882961 compared with placebo on the weight of obese participants.

PF-06882961

PF-06882961

Tab

10 mg, 40 mg, and 100 mg

The effect of various doses of PF-06882961 compared with placebo on the weight of obese participants.

1. At the first visit, the age is 18 years old (or more than 18 years old, the country-specific minimum age of consent)
Male or female participants up to and including 75 years old.  Women who are fertile, but cannot be pregnant, breastfeeding, or participating in trials
When planning to get pregnant. 
Participant type and disease characteristics:
2. Willing and able to comply with all scheduled visits, treatment plans, laboratory tests, lifestyle considerations and other test procedures.
Body mass index (BMI) and weight:
3. Obese participants were defined as having a BMI greater than or equal to 30.0 kg/m2 at the first visit.
4. Weight stability is defined as a weight change of less than 5 kg (as reported by the participant) within 90 days before the first visit.

1. Known intolerance or allergy to glucagon-like peptide-1 receptor (GLP-1R) agonists.
2. Any disease that may affect drug absorption (such as previous bariatric surgery, gastrectomy, or any area of ​​bowel resection; active inflammatory bowel disease or pancreatic insufficiency).
3. Currently or previously diagnosed with type 1 diabetes (T1DM) or type 2 diabetes (T2DM) or secondary diabetes. Note: Women who have a medical history of gestational diabetes and relieved after childbirth are eligible to participate if they meet other qualifications.
4. Within 6 months before the first visit, have myocardial infarction, unstable angina, have undergone arterial revascularization, stroke, New York Heart Association functional classification II-IV heart failure, or transient brain History of ischemic attack.
5. Any malignant tumor that is considered incurable (except localized, treated basal cell carcinoma and skin squamous cell carcinoma) if there is no evidence of cancer recurrence in the past 5 years, the participant is considered cured.
6. According to the judgment of the trial host, a participant with a personal or family history of medullary thyroid cancer or multiple endocrine tumor syndrome type 2, or a participant with suspected medullary thyroid cancer.
7. History of acute or chronic pancreatitis.
8. Suffer from symptomatic gallbladder disease.
9. Medical history or characteristics suggest obesity caused by hereditary or comprehensive obesity, or other endocrine diseases (such as Cushing’s syndrome).
10. A history of severe depression or other serious mental illness (such as schizophrenia or bipolar disorder) in the past two years.
11. There has been any history of attempted suicide in his lifetime.
12. Known history of active liver disease (except non-alcoholic fatty hepatitis), including chronic active hepatitis B or C, or primary biliary cirrhosis.
13. Known history of human immunodeficiency virus (HIV).
14. Other medical or mental illnesses that may increase the risk of trial participation, including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormalities, or the participant is not suitable to participate in the trial as judged by the trial host.
15. For detailed information on the prohibition of previous/concomitant drugs, please refer to the trial plan for details
16. 30 days before the first dose of the trial intervention (or determined according to local requirements) or the trial intervention of this trial
The experimental drug has been administered within 5 half-lives before the first dose of treatment (whichever is longer).
17. Previously known to have participated in the trial of PF-06882961.
18. Obtain a PHQ-9 score greater than or equal to 15 at the first, second, or third visit.
19. At the 1, 2 or 3 visits, answer "yes" to questions 4 or 5 or any behavioral questions on C-SSRS.
20. At the first, second, or third visit before random assignment, the lying down blood pressure after resting for at least 5 minutes is greater than or equal to 160 mmHg (systolic blood pressure) or greater than 100 mmHg (diastolic blood pressure). The blood pressure should be measured three times, and the average of the three BP values ​​should be used to determine the eligibility of the participant.
21. At the 1, 2 or 3 visits before random assignment, the 12-lead ECG showed clinically relevant abnormalities that may affect the safety of participants or the interpretation of trial results (eg QTcF interval> 450 msec, complete left bundle branch Conduction block (LBBB), signs of acute or age uncertain myocardial infarction, ST-T interval suggesting myocardial ischemia, secondary or tertiary atrioventricular block, or severe arrhythmia, including bradycardia or Tachycardia). If the QTcF exceeds 450 msec or the QRS exceeds 120 msec, the ECG should be measured twice and the average of the 3 QTcF or QRS values ​​should be used to determine the eligibility of the participant. Before excluding participants, a physician with experience in interpreting ECGs should read the computer-interpreted ECG results from the beginning.
22. The urine drug test was positive at the first visit. Note: Participants who have prescribed opioids/opioids or benzodiazepines and have reported the use of these drugs to the trial host at the first visit are allowed to participate in the trial, but they must notify the trial commissioner By.
23. Participants who have any of the following abnormalities in the clinical laboratory test at the first return visit after the evaluation of the specific research laboratory of the trial, if deemed necessary, through a single repeated test:
 Glycated hemoglobin (HbA1c) greater than or equal to 6.5%;
 Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration greater than or equal to 2 times the upper limit of normal (ULN)
 The total bilirubin concentration (TBili level) is greater than or equal to 1.5 times the upper limit of normal (ULN);
 Fasting C peptide 0.8 ng/mL;
 Thyroid-stimulating hormone (TSH)> 1.5 times the upper limit of normal (ULN) or  Serum calcitonin> upper limit of normal (ULN);
 Amylase or lipase> upper limit of normal (ULN);
 Fasting blood glucose (FPG) greater than or equal to 126 mg/dL (7 mmol/L);
 Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (calculated by CKD-EPI formula).
24. During the 2-week placebo introduction period before random assignment on day 1, compliance was less than <89% (based on the number of tablets).
25. Participate in a formal weight loss program (such as Weight Watchers) within 90 days before the first visit.
26. In the 6 months before the first visit, the female participant had a regular drinking record of more than 7 glasses per week, and the male participant drank more than 14 glasses per week (1 cup = 5 ounces [150 mL] of wine or 12 ounces of [360] mL] of beer or 1.5 ounces [45 mL] of spirits).
27. Known or suspected use of illegal drugs.
28. Donate about 1 pint (500 mL) or more of blood (excluding donated plasma) within 60 days before random assignment (day 1).
29. Unwilling or unable to comply with the "Lifestyle Considerations" section of the test plan book
30. Live with participants who are currently being screened or in the randomized treatment phase of the trial. Note: If other family members of the participant have failed the screening, or the participant is in the follow-up period of their trial, the participant can be included in the trial.
31. The weight exceeds the maximum measurement limit of the weight scale of the test center, so the weight cannot be accurately assessed.
32. The staff of the test center or Pfizer Pharmaceuticals, as well as the staff of the test center and other family members supervised by the test leader who directly participated in the trial.