a study evaluating daily oral doses of tlc-3595 in participants with insulin resistance

Conditions: Insulin Resistance

Summary: this phase 2a study is designed to evaluate the safety, tolerability, effectiveness, and pharmacokinetics (pk) of tlc-3595 in subjects with insulin resistance.

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).

Eligibility criteria:
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