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

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

Detailed Description
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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).

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

Conditions
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Insulin Resistance

Intervention / Treatment
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* Drug: TLC-3595 Dose 1
* Drug: TLC-3595 Dose 2
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |