Phase 1/1b Study of TLC-6740 in Healthy Subjects and Subjects With Obesity, With or Without Diabetes

Exclusion Criteria

• •Pregnant or lactating subjects
• •Unstable type 2 diabetes (as defined as: HbA1c \> 10.0%; treatment with insulin and/or pioglitazone within 90 days prior to Screening; any history of diabetic ketoacidosis, hyperosmolar state, and/or acutely decompensated blood glucose control; hypoglycemia unawareness, hospitalization due to hypoglycemia, or history of severe hypoglycemia \[requiring outside assistance to regain normal neurologic status\]) (Part F)
• •History of type 2 diabetes diagnosed prior
• •Medical history of type 1 diabetes or latent autoimmune diabetes of adults (LADA)
• •Obesity induced by other endocrinologic disorders (e.g., Cushing syndrome) or diagnosed monogenetic or syndromic forms of obesity (e.g., melanocortin 4 receptor deficiency or Prader-Willi syndrome)
• •Known serious hypersensitivity to tirzepatide or any of the excipients in tirzepatide (Part G)
• •Subjects who have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with the subject's treatment, assessment, or compliance with the protocol
• •Subjects who have received any investigational compound within 30 days or 5 half-lives, whichever is longer, prior to study drug dosing
• •Current alcohol abuse that is judged by the investigator to potentially interfere with the subject's compliance or safety
• •Current substance abuse that is judged by the investigator to potentially interfere with the subject's compliance or safety
• •A positive test result for human immunodeficiency virus (HIV-1) antibody, hepatitis B (HBV) surface antigen, or hepatitis C (HCV) antibody
• •Medical history of drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity)
• •Presence or history of cardiovascular disease, including significant cardiovascular disease (including a history of myocardial infarction based on ECG and/or clinical history), history of cardiac conduction abnormalities (including any history of ventricular tachycardia), congestive heart failure, cardiomyopathy with left ventricular ejection fraction \< 40%, a family history of Long QT Syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years
• •Syncope, palpitations, or unexplained dizziness
• •Implanted defibrillator or pacemaker
• •Medical history of liver disease, including but not limited to alcoholic liver disease, autoimmune disorders (e.g., primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency)
• •Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions
• •History of medical or surgical treatment that permanently alters intestinal absorption (e.g., gastric or intestinal surgery)
• •Subjects who have received vaccination for COVID-19 within 14 days of Admission