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

Launched by ORSOBIO, INC · Apr 19, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called TLC-6740 to see how safe it is and how the body processes it in both healthy individuals and those with obesity, with or without type 2 diabetes. The trial has two parts: one for healthy participants and another for those with obesity. It aims to find out if TLC-6740 can be tolerated well and how it works in the body after taking it in different amounts.

To participate, you need to be between 18 and 70 years old, generally healthy, and have a body mass index (BMI) within a certain range. The study excludes people with unstable diabetes, serious medical conditions, or a history of certain health issues. If you join, you can expect to take the medication and be monitored for any effects, both good and bad. It's important to know that there are specific health requirements to ensure safety, and participants must agree to certain precautions, like using contraception if they are of childbearing potential.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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
• 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
• • Note: Other protocol defined Inclusion/Exclusion criteria may apply.