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

NCT05822544 | Recruiting Phase 1

• 1 other identifier: 6740-CL-101
• Study Type: interventional
• Target: 564
• Locations: 1 country
• Sites: 4

Brief Summary

The phase 1 portion of the study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TLC-6740 after single- and multiple-ascending doses in healthy subjects. The phase 1b portion of the study is designed to assess the safety, tolerability, and PK of TLC-6740 in subjects with obesity, with or without type 2 diabetes mellitus.

Conditions

Healthy Subjects; Obesity; Type 2 Diabetes

Outcome Measures

Primary Outcomes (6)

• Incidence of TLC-6740 treatment-emergent adverse events

  Adverse events (AEs) - severity of the AEs will be graded using the Common Terminology Criteria for AE (CTCAE) (v5.0). The relationship between AEs and the study drug will be indicated as related or not related.

  Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study

• PK of TLC-6740 AUC

  Area under the concentration-time curve

  Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study

• PK of TLC-6740 Cmax

  Maximum plasma concentration

  Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study

• PK of TLC-6740 tmax

  Time to reach Cmax

  Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study

• PK of TLC-6740 t1/2

  Half-life

  Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study

• PK of TLC-6740 CL/F

  Apparent clearance, calculated as dose/AUC0-inf

  Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study

Study Arms (5)

Oral Solution

EXPERIMENTAL

Oral solution of TLC-6740

Drug: TLC-6740 Oral Solution; Other: Placebo Oral Solution

Tablet

EXPERIMENTAL

Tablet formulation of TLC-6740

Drug: TLC-6740 Tablet; Other: Placebo Tablet

Drug Metabolizing Enzyme

EXPERIMENTAL

Oral dose of omeprazole, voriconazole, itraconazole, or rifampicin

Drug: TLC-6740 Tablet; Drug: Drug Metabolizing Enzyme

TLC-6740 + Tirzepatide

EXPERIMENTAL

TLC-6740 tablet + subcutaneous injection of tirzepatide

Drug: TLC-6740 Tablet; Drug: Tirzepatide

Placebo + Tirzepatide

EXPERIMENTAL

TLC-6740 placebo + subcutaneous injection of tirzepatide

Interventions

TLC-6740 Oral Solution DRUG

Oral solution of TLC-6740

Oral Solution

Placebo Oral Solution OTHER

Placebo-to-match oral solution TLC-6740

Oral Solution

TLC-6740 Tablet DRUG

Tablet formulation of TLC-6740

Drug Metabolizing Enzyme; TLC-6740 + Tirzepatide; Tablet

Drug Metabolizing Enzyme DRUG

Oral dose of omeprazole, voriconazole, itraconazole, or rifampicin

Drug Metabolizing Enzyme

Tirzepatide DRUG

Subcutaneous injection of tirzepatide

TLC-6740 + Tirzepatide

Placebo Tablet OTHER

Placebo-to-match tablet formulation of TLC-6740

Tablet

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• OrsoBio, Inc: lead

Study Sites (4)

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

MeSH Terms

Conditions

Obesity; Diabetes Mellitus, Type 2

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• OrsoBio Study Director

  OrsoBio, Inc

  STUDY DIRECTOR

Central Study Contacts

Ryan Huss, MD

CONTACT

650-382-2225; Clinicaltrials_Inquires@orsobio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study consists of seven parts: Part A (single-ascending dose), Part B (multiple-ascending dose), Part C (adaptive single- and/or multiple-ascending dose), Part D (relative bioavailability of a tablet formulation of TLC-6740), Part E (drug-drug interaction study to determine the effect of TLC-6740 on drug metabolizing enzymes), Part F (multiple dose of TLC-6740 in subjects with obesity with or without type 2 diabetes mellitus), and Part G (multiple dose of TLC-6740 in subjects with obesity receiving tirzepatide).

Study Record Dates

• First Submitted: April 7, 2023
• First Posted: April 20, 2023
• Study Start: April 22, 2023
• Primary Completion: February 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: December 18, 2025

Record last verified: 2025-05

Locations

NZ (4)