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

Korábbi kezelés

• History of type 2 diabetes diagnosed prior
• Subjects who have received any investigational compound within 30 days or 5 half-lives, whichever is longer, prior to study drug dosing
• Subjects who have received vaccination for COVID-19 within 14 days of Admission
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Más betegség

• 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
• 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)
• 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)

Laborértékek

• 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)
• 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

Egyéb

• Pregnant or lactating subjects
• 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
• Syncope, palpitations, or unexplained dizziness
• Implanted defibrillator or pacemaker

• Non-smoking, healthy male or female subject between 18 and 55 years of age, inclusive (Parts A-E); male or female subject between 18 and 70 years of age, inclusive (Parts F, G)
• Body mass index (BMI) from 19 to 35 kg/m2, inclusive (Parts A-E); BMI ≥ 30 kg/m2 and ≤ 50 kg/m2 (Parts F, G)
• Estimated glomerular filtration rate (eGFR) ≥ 80 mL/min (Parts A-E); eGFR ≥ 60 mL/min/1.73m2 or eGFR ≥ 45 mL/min/1.73m2, depending on cohort (Parts F, G)
• ALT/AST/ALP ≤ 1 x ULN (Parts A-E); ALT/AST < 3 x ULN, ALP < 1.5 x ULN (Parts F, G)
• Screening laboratory evaluations (hematology, chemistry, and urinalysis) must fall within the normal range of the local laboratory's reference ranges unless the results have been determined by the investigator to have no clinical significance (Parts A-E)
• Subject must have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the investigator
• Females of childbearing potential must have a negative pregnancy test at Screening and clinic admission
• Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception
• Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs