A Study Evaluating Daily Oral Doses of TLC-3595 in Participants With Insulin Resistance

A Phase 2a Study Evaluating the Safety, Tolerability, and Efficacy of TLC-3595 in Subjects With Insulin Resistance

This Phase 2a study is designed to evaluate the safety, tolerability, effectiveness, and pharmacokinetics (PK) of TLC-3595 in subjects with insulin resistance.

Study Overview

• Status: Recruiting
• Conditions: Insulin Resistance
• Intervention / Treatment: Drug: Placebo; Drug: TLC-3595 Dose 1; Drug: TLC-3595 Dose 2

Detailed Description

This is a multicenter, double-blind, randomized study. Participants will be randomized to one of three treatment arms, to receive one of the two doses of TLC-3595 (or matching placebo).

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2

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, 0626
    • Recruiting
    • OrsoBio Research Site
  • Auckland, New Zealand, 1010
    • Recruiting
    • OrsoBio Research Site
  • Auckland, New Zealand, 1010
    • Recruiting
    • OrsoBio Reseach Site
  • Christchurch, New Zealand, 8011
    • Recruiting
    • OrsoBio Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female between 18-70 years of age, inclusive, at Screening
• BMI ≥ 28 kg/m2 at Screening
• Diagnosis of insulin resistance based on HOMA-IR > 2.84 at Screening or a confirmed diagnosis of type 2 diabetes mellitus
• Screening laboratory evaluations (hematology, chemistry, and urinalysis) must fall within the protocol-defined ranges
• A 12-lead electrocardiogram (ECG) at Screening that is normal or with abnormalities that are considered not clinically significant by the investigator
• Female subjects of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1 prior to first dose of study drug
• Male and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception

Exclusion Criteria:

• HbA1c > 10% at Screening
• Weight loss > 5% weight during the 90 days prior to Screening
• 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
• A positive test result for human immunodeficiency virus (HIV-1) antibody, hepatitis B (HBV) surface antigen, or hepatitis C (HCV) antibody
• Unstable cardiovascular disease as defined by any of the following: unstable angina within 6 months prior to Screening; myocardial infarction, coronary artery bypass graft surgery, or coronary angioplasty within 6 months prior to Screening; transient ischemic attack or cerebrovascular accident within 6 months prior to Screening; obstructive valvular heart disease or hypertrophic cardiomyopathy; congestive heart failure (NYHA Class ≥ 2); 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. A history of nonalcoholic fatty liver disease (NAFLD), including hepatic steatosis or nonalcoholic steatohepatitis (NASH) is permitted.
• History of intestinal resection or malabsorptive condition that may limit the absorption of study drug
• Presence of severe peptic ulcer, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions at Screening, in the opinion of the investigator
• Any scheduled surgery during the trial period, excluding minor surgical procedures performed under local anesthesia, in the opinion of the investigator
• History of malignancy within 5 years prior to Screening except adequately treated carcinoma in situ of the cervix, and/or squamous cell cancer, or other localized non-melanoma skin cancer
• History of significant drug allergy, such as anaphylaxis or significant drug sensitivity, in the opinion of the investigator
• Known hypersensitivity to study drug, its metabolites, or formulation excipients
• Presence of any medical condition that could, in the opinion of the investigator, compromise the subject's ability to participate in the study, including a history of substance abuse or a psychiatric disorder, including any subject with a psychiatric hospital admission or emergency room visit in the 2 years prior to Screening
• Any laboratory abnormality that in the opinion of the investigator could adversely affect the safety of the subject or impair assessment of study results
• Subjects on any oral medication with a narrow therapeutic window (e.g., warfarin, digoxin, tricyclic antidepressants, lithium, aminophylline, theophylline, and anticonvulsants)
• Medications or therapies prescribed or taken over-the-counter for weight loss, in the 90 days prior to Screening.
• Receipt of vaccination for COVID-19 or any other live vaccine within 14 days of planned dosing of study drug

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: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TLC-3595 Dose 1; Oral dose of TLC-3595 Dose 1	Drug: TLC-3595 Dose 1; Tablets administered orally
Experimental: TLC-3595 Dose 2; Oral dose of TLC-3595 Dose 2	Drug: TLC-3595 Dose 2; Tablets administered orally
Placebo Comparator: Placebo; Oral dose of placebo-to-match	Drug: Placebo; Tablets administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in insulin sensitivity	Oral glucose tolerance test will be used to measure insulin sensitivity.	Through study completion, up to Day 84 of the study
Incidence of TLC-3595 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 84 of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fasting plasma glucose	Blood samples were collected at specific time points for the laboratory evaluation to assess the fasting glucose level.	Baseline and Week 4
Change in fasting insulin	Blood samples were collected at specific time points for the laboratory evaluation to assess the fasting insulin level.	Baseline and Week 4
Change in fructosamine	Blood samples were collected at specific time points for the laboratory evaluation to assess the fructosamine level.	Baseline and Week 4
Change in glycated hemoglobin (HbA1c)	Blood samples were collected at specific time points for the laboratory evaluation to assess the HbA1c level.	Baseline and Week 4
Change in low-density lipoprotein cholesterol (LDL-C)	Blood samples were collected at specific time points for the laboratory evaluation to assess the LDL-C level.	Baseline and Week 4
Change in high-density lipoprotein cholesterol (HDL-C)	Blood samples were collected at specific time points for the laboratory evaluation to assess the HDL-C level.	Baseline and Week 4
Change in triglycerides (TG)	Blood samples were collected at specific time points for the laboratory evaluation to assess the TG level.	Baseline and Week 4
Change in total carnitines	Blood samples were collected at specific time points for the laboratory evaluation to assess the total carnitines level.	Baseline and Week 4
Change in free carnitines	Blood samples were collected at specific time points for the laboratory evaluation to assess the free carnitines level.	Baseline and Week 4
Change in β-hydroxybutyrate	Blood samples were collected at specific time points for the laboratory evaluation to assess the β-hydroxybutyrate level.	Baseline and Week 4
Change in adiponectin	Blood samples were collected at specific time points for the laboratory evaluation to assess the adiponectin level.	Baseline and Week 4
Change in DHEA-S	Blood samples were collected at specific time points for the laboratory evaluation to assess the DHEA-S level.	Baseline and Week 4
Change in body composition	Dual-energy X-Ray absorptiometry (DEXA) will be performed at specific time points to evaluate measures of body composition.	Baseline and Week 4
Change in fat fraction in liver and muscle	Abdominal magnetic resonance imaging (MRI) will be performed at specific time points to evaluate fat fractions of the liver and skeletal muscles.	Baseline and Week 4
Drug concentration	Blood samples were collected at specific time points to assess the drug concentration level.	Week 2 and Week 4

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2023
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: December 16, 2022
• First Submitted That Met QC Criteria: December 16, 2022
• First Posted (Actual): December 27, 2022

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: 3595-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