Evaluating TLC-6740 in healthy individuals and those with obesity or diabetes

A Phase 1/1b Study of Single and Multiple Ascending Doses of TLC 6740 in Healthy Subjects, Including Evaluation of Food Effect and Potential Drug-Drug Interactions, and Preliminary Safety and Efficacy in Subjects With Obesity, With or Without Diabetes

This study is testing a new drug called TLC-6740 in healthy people and those with obesity or diabetes to see how safe it is and how it works in the body.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 564 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: OrsoBio, Inc (Industry-sponsored)
• Locations: 4 sites (Auckland and 3 other locations)
• Trial ID: NCT05822544 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of TLC-6740 in both healthy subjects and individuals with obesity, with or without type 2 diabetes. The study is divided into multiple parts, including single and multiple ascending doses, relative bioavailability assessments, and drug-drug interaction studies. Up to 180 obese participants and 48 healthy subjects will be recruited to evaluate the effects of TLC-6740 and its interaction with other medications. The study also investigates how food intake affects the pharmacokinetics of TLC-6740.

Who should consider this trial

Good fit: Ideal candidates include healthy adults aged 18-55 and obese individuals aged 18-70 with a BMI of 30-50.

Not a fit: Patients with significant liver enzyme abnormalities or those outside the specified age and BMI ranges may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new treatment options for obesity and type 2 diabetes.

How similar studies have performed: Other studies have shown promise with similar pharmacological approaches, but this specific compound is novel.

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.

Where this trial is running

Auckland and 3 other locations

• OrsoBio Auckland Research Site 1 — Auckland, New Zealand (Recruiting)
• OrsoBio Auckland Research Site 2 — Auckland, New Zealand (Recruiting)
• OrsoBio Auckland Research Site 3 — Auckland, New Zealand (Recruiting)
• OrsoBio Research Site — Christchurch, New Zealand (Recruiting)

Study contacts

• Study coordinator: Ryan Huss, MD

Conditions Healthy Subjects; Obesity; Type 2 Diabetes