A Clinical Trial of TQF3250 Capsules in Overweight/Obese Trial Participants With Poor Weight Control Through Simple Lifestyle Intervention

Inclusion criteria

• Key inclusion criteria:

• During screening, trial participants must be aged 18 to 65 (inclusive), and can be male or female;
• During screening, obese individuals with a BMI of 28 to less than 40 kg/m2, or overweight individuals with a BMI of 24 to less than 28 kg/m2 accompanied by at least one of the weight-related comorbidities.
• According to the self-reported information of the trial participants, they had undergone at least 3 months of simple lifestyle intervention before screening, and their weight change in the past 3 months was less than 5%.
• Women of childbearing age should agree to take effective contraceptive measures during the study period and for 6 months after its completion (note: oral hormonal contraceptives should not be relied upon solely for contraception), and they must have a negative blood pregnancy test within 7 days prior to study enrollment; men should agree to take effective contraceptive measures during the study period and for 6 months after its completion.
• Volunteer to sign the informed consent form and are willing to strictly adhere to the requirements and restrictions outlined in the informed consent form and this protocol throughout the entire research period, including but not limited to: managing diet and exercise lifestyle, taking the study medication as scheduled, keeping a research diary, and completing relevant questionnaires.

Exclusion criteria

• Key exclusion criteria:

• Trial participants whom researchers suspect may be allergic to the study drug or its components, or who have an allergic constitution;
• Participants who have used glucagon-like peptide-1 receptor (GLP-1R) agonists, GLP-1R/glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists, or GLP-1R/glucagon receptor (GCGR) agonists within the previous 3 months prior to screening;
• Screen for medications that have been used or are currently being used within the previous 3 months and have an impact on body weight, including: steroid hormone medications (administered intravenously, orally, or intra-articularly), metformin, sodium-glucose co-transporter 2 (SGLT-2) inhibitors, thiazolidinediones (TZD), tricyclic antidepressants, medications for psychiatric disorders or sedatives (such as imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid, valproic acid derivatives, lithium salts), etc;
• Screen for individuals who have consumed Chinese herbal medicines, health supplements, or meal replacements that affect body weight within the previous 3 months;
• Screen for individuals who have used or are currently using weight-loss drugs within the previous 3 months, such as: sibutramine hydrochloride, orlistat, phenylbutyrate, phenylpropanolamine, clobenzolide, phentermine, amfepramone, lorcaserin, phentermine/topiramate combination, naltrexone/bupropion combination, etc;
• Participants who have participated in other clinical trials (and have received trial drug treatment) within the previous 3 months;
• Patients with previously diagnosed diabetes (including type 1 or type 2 diabetes, etc.);
• Screen for patients with fasting venous blood glucose levels ≥7.0 mmol/L or glycated hemoglobin levels ≥6.5%;
• Participants who have experienced unexplained hypoglycemic events (blood glucose <3.9 mmol/L) within the previous 1 month before screening;
• Have previously undergone or plan to undergo weight loss surgery during the study period (excluding acupuncture and moxibustion for weight loss, liposuction, or abdominal liposuction performed more than 1 year before screening);
• Obesity caused by secondary diseases or medications, including: elevated cortisol hormone levels (e.g., Cushing's syndrome), obesity caused by pituitary and hypothalamic damage, and obesity caused by diagnosed monogenic or syndromic conditions (e.g., melanocortin 4 receptor deficiency or Prader-Willi syndrome);
• Any clinically significant endocrine system disease (such as hyperthyroidism, acromegaly, Cushing's syndrome, etc.) that the investigator deems unsuitable for participation in the study (if the investigator deems the condition stable, and the aforementioned diseases have been stably treated with medication for more than 3 months, and are not expected to have a significant impact on body weight, enrollment may be allowed);
• Previous history of depression; suicidal tendencies or suicide attempts, or previous history of severe mental illnesses, such as schizophrenia, bipolar disorder, etc;
• Resting blood pressure: Systolic Blood Pressure≥ 160 mmHg or < 90 mmHg, and/or diastolic blood pressure≥ 100 mmHg (a retest is allowed after 10 minutes, and the retest value shall prevail), or new/changed antihypertensive medications or adjusted antihypertensive medication doses within 4 weeks before screening;
• Having any malignant tumor within the past 5 years (excluding basal cell carcinoma that has undergone curative treatment and is considered cured);
• Before screening, individuals with a history of major cardiovascular and cerebrovascular diseases within the past 6 months are defined as:

• History of myocardial infarction, unstable angina, coronary artery angioplasty or bypass surgery, valvular heart disease or valvular heart surgery, clinically significant arrhythmia, transient ischemic attack, or cerebrovascular accident; or
• Congestive heart failure with New York Heart Association (NYHA) classification of III or IV;
• Screen for hemorrhagic or ischemic stroke or transient ischemic attack that occurred within the previous 6 months;
• Individuals with a history or family history of medullary thyroid cancer, multiple endocrine neoplasia (MEN) 2A or 2B, or genetic diseases that are prone to induce medullary thyroid cancer during screening;
• During screening, patients with a history of acute or chronic pancreatitis, pancreatic injury, or clinically significant gallbladder or bile duct diseases (excluding gallbladder polyps that do not require clinical intervention) are excluded;
• Previously had clinically significant gastric emptying abnormalities (such as gastric outlet obstruction), severe chronic gastrointestinal diseases (such as active ulcer within 6 months before screening), long-term use of drugs with direct effects on gastrointestinal motility, or underwent gastrointestinal surgery (excluding endoscopic resection of gastrointestinal polyps, etc.);
• Individuals with physical deformities or mutilations, making it impossible to accurately determine their height, weight, and other indicators;
• Participants who have undergone major or medium-sized surgery, severe trauma, or severe infection within one month prior to screening, and are deemed unsuitable for participation in this study by the investigator;
• History of organ transplantation, or history of other acquired or congenital immune system diseases;
• During the trial, there were anticipated surgeries, except for outpatient surgeries that the researchers determined had no impact on the safety of trial participants and the trial results;
• During screening, if the virological test indicates any of the following conditions:

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• HCV antibody is positive, and the detection value of HCV viral load (HCV RNA) exceeds the upper limit of normal range;
• HBsAg is positive, and the HBV DNA detection value exceeds the upper limit of normal range;
• HIV-positive;
• Active syphilis: Treponema pallidum antibody is positive during the screening period, and the non-treponemal serological test is also positive.

• Screen for individuals who have received or plan to receive live vaccines or attenuated live vaccines within 30 days prior to the study. Inactivated vaccines (including inactivated influenza vaccines) are not subject to this restriction, but the vaccination status should be accurately recorded.

• Screen for individuals who have regularly consumed alcohol within the previous 3 months, specifically those who have consumed more than 14 units of alcohol per week (1 unit equals 360 mL of beer, 45 mL of spirits with 40% alcohol content, or 150 mL of wine); or those who have exhibited clinically significant abnormalities in blood alcohol testing during the screening period; or those who are unable to adhere to the protocol's prohibition on alcohol consumption; 28. Screen out smokers who have smoked more than 10 cigarettes per day for the previous 3 months or who cannot quit smoking during the pharmacokinetic intensive blood sampling period; 29. Individuals with a history of drug abuse, drug dependence, or use of drugs within the previous year, or those who tested positive for drugs in urine screening prior to drug administration, shall be screened out; 30. During screening, serum calcitonin should be ≥20ng/L; 31. During screening, the alanine aminotransferase (ALT) level must be ≥2.0× ULN and/or the aspartate aminotransferase (AST) level must be ≥2.0× ULN and/or the total bilirubin level must be ≥1.5× ULN and/or the alkaline phosphatase (ALP) level must be ≥2.0× ULN; 32. During screening, the glomerular filtration rate (eGFR) should be less than 60 mL/min/1.73 m2, calculated according to the CKD-EPI 2021 formula; 33. Screen for participants with fasting triglyceride levels ≥5.65 mmol/L (500 mg/dl). If the participants are undergoing lipid-lowering treatment, the type and dosage of medication should be stable for at least 30 days before screening, and in principle, they should remain unchanged during the study period; 34. During screening, the blood amylase or lipase level should be greater than 1.5× ULN; 35. During screening, the 12-lead electrocardiogram shows a heart rate of <50 beats per minute or >100 beats per minute (a retest is allowed after 10 minutes, and the retest value shall prevail); 36. During screening, the following clinically significant abnormalities in 12-lead electrocardiograms (ECGs) are considered: second-degree or third-degree atrioventricular block, long QT syndrome or QTcF >450ms, PR interval <120ms or PR interval >220ms, QRS >120ms, left or right bundle branch block, pre-excitation syndrome, or other severe arrhythmias requiring treatment; 37. History of other risk factors for Torsade de Pointes (TdP) ventricular tachycardia, such as hypokalemia at screening, family history of Long QT Syndrome, or concurrent medication use that prolongs the QT/QTc interval at screening; 38. Individuals who have donated blood and/or lost blood volume ≥400mL within the previous 3 months, or have undergone bone marrow donation, or suffer from anemia-related diseases such as hemoglobinopathy, hemolytic anemia, sickle cell anemia, or have a hemoglobin level <110g/L (male) or <100g/L (female) before screening; 39. During screening, if any of the following conditions exist:

a. Use of strong or moderate CYP3A4 inhibitors or inducers within 28 days before screening, including but not limited to rifampin, rifapentine, carbamazepine, phenytoin, phenobarbital, St. John's wort, itraconazole, ketoconazole, voriconazole, ritonavir, cobistat, clarithromycin, etc; b. Those who are currently using simvastatin during screening and cannot discontinue it and switch to an alternative treatment regimen approved by the investigator; for those who have previously used simvastatin, they should discontinue it before screening and switch to an alternative treatment regimen approved by the investigator, and the alternative treatment regimen must be stable for at least 30 days before enrollment.

• Researchers believe that trial participants who possess any other factors that may affect the efficacy or safety evaluation of this study are not suitable to participate in this study.