Investigation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LIM-0705 in Male Subjects With Impaired Glucose Tolerance

Study Overview
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Brief Summary
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LIM-0705 will gain results on the effects of LIM-0705 on Male Subjects with Impaired Glucose Tolerance

Official Title
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A Single-Blind,Randomized,Placebo-Controlled Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Exploratory Pharmacodynamics of LIM-0705 in Male Subjects With Impaired Glucose Tolerance

Conditions
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Impaired Glucose Tolerance

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males, age 18-70 years old Measured waist circumference to hip circumference ratio >0.90 Body mass index (BMI) of 27 - 40 kg/m2 Screening and Day -1 capillary glucose measurement between 110-160 mg/dL (6.1-8.9 mmol/L) after a 12 hour fast Screening and Day -1 OGTT with a 2 hour post-glucose measurement ≥140 mg/dL (7.8 mmol/L) after a 12 hour fast Screening HbA1c > 6 and ≤ 7.5% Subjects must be in reasonably good health as determined by pre-study medical history, physical examination, 12-lead ECG, and the following laboratory measures: Electrolytes, ALP, LDH, creatinine, and urea must be within normal range without medication Urinalysis within normal limits Willing to remain in confinement at the clinical study unit for up to 18 days/17 nights and to return to the unit as specified for additional assessments Willing to consume only the food that is provided by the clinical study unit Non-smokers or social smokers (defined as fewer than 5 cigarettes per week) willing to abstain from smoking for the duration of study Willing to abstain from alcohol-containing, grapefruit-containing, or caffeine-containing foods or beverages Able to read, understand and follow the study instructions Agree to use of two effective methods of contraception Exclusion Criteria: Allergy to onions or red wine Strict vegetarians (i.e., subjects who do not eat meat, fish, fowl, or dairy) Use of any non-study medication(s) during the study period other than those approved by the Investigator for treatment of an adverse event (AE) Use of chemotherapy agents or history of cancer, other than non-metastatic non-melanoma skin cancer that has been completely excised, within five (5) years prior to the Screening visit Use of any dietary aids or foods known to modulate drug metabolizing enzymes (e.g., St. John's Wort, grapefruit juice) within 4 days of randomization History of bacterial or viral infection requiring treatment with antibiotics or antivirals within 30 days of randomization Difficulty in swallowing oral medications History of seizure disorder Moderate to severe gastro-esophageal reflux disease History of arrhythmia Cognitive or psychiatric disorders, or any other condition that could interfere with compliance with study procedures and/or confinement in a clinical study unit Baseline liver enzymes greater than the upper limit of normal Baseline creatine phosphokinase (CPK) greater than 2.5x the upper limit of normal History of drug or alcohol abuse Use of any other investigational drug within 30 days of randomization or investigational biologic within 180 days of randomization Use of over-the-counter (OTC) medications or nutraceuticals, excluding routine vitamins, within 14 days of randomization or 5 half-lives of the drug, whichever is longer Use of prescription pharmaceuticals within 30 days of randomization Donation and/or receipt of any blood or blood products within 90 days of randomization Current gastrointestinal (GI), renal, hepatic, or coagulant disorder within 12 months of randomization History of peptic or duodenal ulcer or GI bleed Subjects with Gilbert's Syndrome Subjects with positive drug or alcohol screen Subject positive for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

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: A<br>750 mg of LIM-0705 BID for 14 days. Up to 20 subjects. | Drug: LIM-0705<br>* Oral solution 750 mg LIM 0705 BID for 14 days.<br>|
| Placebo Comparator: B<br>Placebo BID for 14 days. Up to 10 subjects. | Drug: Placebo<br>* Oral solution placebo BID for 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of LIM-0705 on glucose metabolism, lipid metabolism and renal function in subjects with impaired glucose tolerance | Assessment of glucose metabolism will be based on monitoring of overnight-fasting glucose levels and on performance of an Oral Glucose Tolerance Test (OGTT) Assessment of lipid metabolism will be based on 12 hour-fasting lipid profiles (including LDL, HDL, total cholesterol, free fatty acids, and triglycerides) Assessment of renal function will be performed by monitoring serum BUN and creatinine levels | approx. 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events and pharmacokinetics of LIM-0705 and its major metabolite | To evaluate the incidence of treatment emergent adverse events; as well as changes in physical examination findings, vital signs, ECGs, and clinical laboratory tests (serum chemistry, hematology urinalysis, and coagulation) To characterize the pharmacokinetics of LIM-0705 and its major metabolite | approx. 1 month |