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

OrsoBio

Status and phase: Active, not recruiting; Phase 2

Conditions: Insulin Resistance

Treatments: Drug: TLC-3595 Dose 1; Drug: Placebo; Drug: TLC-3595 Dose 2

Study type: Interventional

Funder types: Industry

Identifiers

NCT05665751

3595-CL-101

Details and patient eligibility

About

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

Full 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).

Enrollment: 76 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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76 participants in 3 patient groups, including a placebo group

TLC-3595 Dose 1

Experimental group

Description:

Oral dose of TLC-3595 Dose 1

Treatment:

Drug: TLC-3595 Dose 1

TLC-3595 Dose 2

Experimental group

Description:

Oral dose of TLC-3595 Dose 2

Treatment:

Drug: TLC-3595 Dose 2

Placebo

Placebo Comparator group

Description:

Oral dose of placebo-to-match

Treatment:

Drug: Placebo