Clinical trial NCT05665751: A Study Evaluating Daily Oral Doses of TLC-3595 in Participants With Insulin Resistance
Official title: A Phase 2a Study Evaluating the Safety, Tolerability, and Efficacy of TLC-3595 in Subjects With Insulin Resistance
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Insulin Resistance
Lead sponsor: OrsoBio, Inc
Sponsor class: INDUSTRY
First posted: 2022-12-27
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Primary outcomes:
measure: Change in insulin sensitivity
timeFrame: Through study completion, up to Day 84 of the study
measure: Incidence of TLC-3595 treatment-emergent adverse events
timeFrame: Through study completion, up to Day 84 of the study
Secondary outcomes:
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: OrsoBio Research Site
city: Auckland
country: New Zealand
facility: OrsoBio Reseach Site
city: Auckland
country: New Zealand
facility: OrsoBio Research Site
city: Christchurch
country: New Zealand
facility: OrsoBio Research Site
Study officials:
affiliation: OrsoBio, Inc
name: OrsoBio Study Director
role: STUDY_DIRECTOR
References: