Safety, Tolerability, PK, and PD of LIM-0705 in Subjects With Impaired Glucose Tolerance or Abnormal HOMA-IR

Study Overview
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Brief Summary
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Preliminary research suggests that LIM-0705 improves insulin sensitivity with neutral effects on weight in obese and diabetic rodent models. Results from a Phase 1b clinical study, conducted in healthy volunteers, indicate that LIM-0705 and a major metabolite may be potential insulin sensitizers by OGTT.

Detailed Description
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The primary objective of the study is to evaluate the safety and tolerability of LIM-0705 administered for 28 days in adult males and females with impaired glucose tolerance or abnormal HOMA-IR. Secondary Objectives include: examine the pharmacokinetics (PK) of LIM-0705 explore the pharmacodynamics (PD) of LIM-0705 in obese adult males and females with impaired glucose tolerance (defined as two-hour plasma glucose levels of ≥140 to ≤199 mg per dL [7.8 to 11.06 mmol/L] on the 75-g oral glucose tolerance test [OGTT]) or abnormal HOMA-IR (HOMA-IR value ≥ 2.5) as measured by change in response to hyperinsulinemic clamp, mixed-meal tolerance test (MMTT) between Days -2 and 27 explore the effect of LIM-0705 on fasting lipid, insulin and glucose profiles compared to baseline levels

Official Title
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A Randomized, Single-Blind, Placebo-Controlled Phase 2 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LIM-0705 in Subjects With Impaired Glucose Tolerance or Abnormal HOMA-IR

Conditions
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Insulin Resistance, Impaired Glucose Tolerance

Intervention / Treatment
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* Drug: LIM-0705
* Drug: Placebo capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: males and females, age 18-75 years old, able and willing to provide written informed consent to participate in the study obesity-induced impaired glucose tolerance or abnormal HOMA-IR waist circumference of 40 inches or greater (men) or 35 inches or greater (women) good physical health based on EKG, electrolytes, LDH, creatinine, urea, AST, ALT, alkaline phosphatase, and renal function male subjects who are sexually active with a female partner of childbearing age must agree to use of 2 effective methods of contraception, including the use of a condom, throughout the course of the study or provide proof of surgical sterility. The second method of contraception must be the use by their female partners of any of the following: a diaphragm with spermicide, a cervical cap with spermicide, an IUD, a female condom, or an approved hormonally based contraceptive (e.g., an oral, transdermal, or implanted estrogen or progestin). Female subjects must be post menopausal or surgically sterile. Exclusion Criteria: BMI equal to or greater than 40 kg/m2 allergy to onions or red wine strict vegetarians use of any non-study medications other than thyroid replacement hormone or anti-hypertensives. Use of cardesarten cilexetil is not permitted. Note: acetaminophen should not be administered. use of chemotherapy agents or history of cancer, other than non-metastatic non-melanoma skin cancer that has been completely excised, within 5 years prior to the screening visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 600 mg LIM-0705 BID for 28 days<br> | Drug: LIM-0705<br> <br> |
| Placebo Comparator: Placebo LIM-0705 for 28 days<br> | Drug: Placebo capsules<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the safety (number of subjects with adverse events) of LIM-0705 administered to adult males and females with impaired glucose tolerance or abnormal HOMA-IR |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examine the pharmacokinetics (PK) of LIM-0705 as measured by area under the curve (AUC). |  | 28 days | 
| Explore the pharmacodynamics (PD) of LIM-0705 in obese adult males and females with impaired glucose tolerance or abnormal HOMA-IR as measured by change in response to hyperinsulinemic clamp, mixed-meal tolerance test (MMTT) between Days -2 and 27 |  | 28 days | 
| Explore the effect of LIM-0705 on fasting lipid, insulin and glucose profiles compared to baseline levels |  | 28 days | 
| Evaluate the tolerability (BID) of LIM-0705 administered to adult males and females with impaired glucose tolerance or abnormal HOMA-IR |  | 28 days |