A Study Evaluating Daily Oral Doses of TLC-3595 in Participants With Insulin Resistance
Study Details
Study Description
Brief Summary
This is a Phase 2a, multicenter, double-blind, randomized study designed to evaluate the safety, tolerability, effectiveness, and pharmacokinetics of TLC-3595 activity in participants with insulin resistance.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Participants will be randomized to one of three treatment arms, to receive one of the two doses of TLC-3595 (or matching placebo). Every participant in each treatment arm will receive 2 oral tablets to be taken once daily for 28 consecutive days with water. The dose levels for each treatment arm are; Group 1 participants (n = 20) will receive Dose 1 of TLC-3595, Group 2 participants (n = 20) will receive Dose 2 of TLC-3595 and Group 3 participants (n = 10) will receive placebo.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TLC-3595 Dose 1 Subjects will receive 12.5 mg of TLC-3595 once daily for 28 days |
Drug: TLC-3595 Dose 1
Tablets administered orally
|
| Experimental: TLC-3595 Dose 2 Subjects will receive 25 mg of TLC-3595 once daily for 28 days |
Drug: TLC-3595 Dose 2
Tablets administered orally
|
| Placebo Comparator: Placebo Subjects will receive placebo-to-match TLC-3595 once daily for 28 days |
Drug: Placebo
Tablets administered orally
|
Outcome Measures
Primary Outcome Measures
- Change in insulin sensitivity [Baseline and Week 4]
Oral glucose tolerance test will be used to measure insulin sensitivity.
- Safety and tolerability measurements throughout 4 weeks by treatment emergent adverse events (TEAEs) [4 weeks]
Incidence and severity of TEAEs
Secondary Outcome Measures
- Change in fasting plasma glucose [Baseline and Week 4]
Blood samples were collected at specific time points for the laboratory evaluation to assess the fasting glucose level.
- Change in fasting insulin [Baseline and Week 4]
Blood samples were collected at specific time points for the laboratory evaluation to assess the fasting insulin level.
- Change in fructosamine [Baseline and Week 4]
Blood samples were collected at specific time points for the laboratory evaluation to assess the fructosamine level.
- Change in glycated hemoglobin (HbA1c) [Baseline and Week 4]
Blood samples were collected at specific time points for the laboratory evaluation to assess the HbA1c level.
- Change in low-density lipoprotein cholesterol (LDL-C) [Baseline and Week 4]
Blood samples were collected at specific time points for the laboratory evaluation to assess the LDL-C level.
- Change in high-density lipoprotein cholesterol (HDL-C) [Baseline and Week 4]
Blood samples were collected at specific time points for the laboratory evaluation to assess the HDL-C level.
- Change in triglycerides (TG) [Baseline and Week 4]
Blood samples were collected at specific time points for the laboratory evaluation to assess the TG level.
- Change in total carnitines [Baseline and Week 4]
Blood samples were collected at specific time points for the laboratory evaluation to assess the total carnitines level.
- Change in free carnitines [Baseline and Week 4]
Blood samples were collected at specific time points for the laboratory evaluation to assess the free carnitines level.
- Change in β-hydroxybutyrate [Baseline and Week 4]
Blood samples were collected at specific time points for the laboratory evaluation to assess the β-hydroxybutyrate level.
- Change in adiponectin [Baseline and Week 4]
Blood samples were collected at specific time points for the laboratory evaluation to assess the adiponectin level.
- Change in DHEA-S [Baseline and Week 4]
Blood samples were collected at specific time points for the laboratory evaluation to assess the DHEA-S level.
- Change in body composition [Baseline and Week 4]
Dual-energy X-Ray absorptiometry (DEXA) will be performed at specific time points to evaluate measures of body composition.
- Change in fat fraction in liver and muscle [Baseline and Week 4]
Abdominal magnetic resonance imaging (MRI) will be performed at specific time points to evaluate fat fractions of the liver and skeletal muscles.
- Drug concentration [Week 2 and Week 4]
Blood samples were collected at specific time points to assess the drug concentration level.
Eligibility Criteria
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
-
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 ≥ 7.5% 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)
-
Treatments for insulin resistance or diabetes, including metformin, or medications or therapies for weight loss, in the 90 days prior to Screening
-
Contraindications or inability to complete MRI scanning (e.g., presence of permanent pacemakers, implanted cardiac devices, claustrophobia, weight restrictions, etc.)
-
Receipt of vaccination for COVID-19 or any other live vaccine within 14 days of planned dosing of study drug
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New Zealand Clinical Research | Christchurch | New Zealand | 8011 |
Sponsors and Collaborators
- OrsoBio, Inc
Investigators
- Principal Investigator: Russell Scott, MD, New Zealand Clinical Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 3595-CL-101