Phase 1/1b Study of TLC-6740 in Healthy Subjects and Subjects With Obesity

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

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Healthy Subjects
• Intervention / Treatment: Other: Placebo; Drug: TLC-6740 Oral Solution; Drug: TLC-6740 Tablet; Drug: Drug Metabolizing Enzyme

Detailed Description

The primary objectives are to assess the safety, tolerability, and plasma PK of TLC-6740 in healthy subjects and subjects with obesity. The exploratory objective is to evaluate the PD of TLC-6740 in healthy subjects and subjects with obesity. This study is comprised of six 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), and Part F (phase 1b). Up to 48, 50, 50, 8, and 20 healthy subjects will be recruited in Parts A, B, C, D, and E, respectively. Up to 60 obese subjects will be recruited in Part F. The effect of food on TLC-6740 PK will also be evaluated in this study.

• Study Type: Interventional
• Enrollment (Estimated): 236
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ryan Huss, MD; Phone Number: 650-382-2225; Email: Clinicaltrials_Inquires@orsobio.com

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Recruiting
    • OrsoBio Research Site
  • Christchurch, New Zealand
    • Recruiting
    • OrsoBio Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 (Part F)
• Body mass index (BMI) from 19 to 35 kg/m2, inclusive (Parts A-E); BMI ≥ 30 kg/m2 (Part F)
• Estimated glomerular filtration rate (eGFR) ≥ 80 mL/min (Parts A-E); eGFR ≥ 60 mL/min (Part F)
• Normal liver biochemistry tests (Parts A-E)
• 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
• HbA1c > 9.5% (Part F)
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Solution; Oral solution of TLC-6740	Drug: TLC-6740 Oral Solution; Oral solution of TLC-6740
Experimental: Tablet; Tablet formulation of TLC-6740	Drug: TLC-6740 Tablet; Tablet formulation of TLC-6740
Placebo Comparator: Placebo; Oral dose of TLC-6740 placebo-to-match	Other: Placebo; Placebo-to-match
Experimental: Drug Metabolizing Enzyme; Oral dose of omeprazole, voriconazole, or itraconazole	Drug: Drug Metabolizing Enzyme; Oral dose of omeprazole, voriconazole, or itraconazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 87 (Part F) 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 87 (Part F) 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 87 (Part F) 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 87 (Part F) 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 87 (Part F) 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 87 (Part F) of the study

Collaborators and Investigators

• Sponsor: OrsoBio, Inc
• Investigators: Study Director: OrsoBio Study Director, OrsoBio, Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: April 7, 2023
• First Submitted That Met QC Criteria: April 19, 2023
• First Posted (Actual): April 20, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: 6740-CL-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No