Adult Subjects With Uncontrolled Type 2 Diabetes

Study Overview
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Brief Summary
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A Multi-center, Double Blind, Randomized, Placebo-controlled, Parallel Group Phase IIa Study of MLR-1023 in Adult Subjects With Uncontrolled Type 2 Diabetes

Detailed Description
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Objectives To assess the safety, tolerability and initial anti-diabetic activity of MLR-1023 in subjects with uncontrolled mild to moderate type 2 diabetes mellitus To evaluate the pharmacokinetics of MLR-1023 and the major metabolite, MLR-1023-M1 following 28 days of repeat dosing Design and Outcomes The study is a randomized, double blind, placebo-controlled, parallel group study of MLR-1023 in adult subjects with uncontrolled type 2 diabetes mellitus who are on diet and exercise therapy. A subset of subjects per dose group will have additional samples analyzed to measure signs of MLR-1023.

Official Title
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A Multi-center, Double Blind, Randomized, Placebo-controlled, Parallel Group Phase IIa Study of MLR-1023 in Adult Subjects With Uncontrolled Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: MLR-1023


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with uncontrolled T2DM who have received diet and exercise therapy for at least 3 months prior to screening, aged ≥ 18 - ≤ 75 years Females must be post-menopausal, unable to conceive, or test negative for pregnancy via blood test and use barrier contraception BMI ranging from ≥ 20 to ≤ 40 kg/m2 Fasting plasma glucose values of up to 240 mg/dL at screening, after wash-out (visit 2) and after placebo run-in (visit 3) (i) naïve or (ii) currently using and discontinued metformin or (iii) no prior exposure to anti-diabetic agents other than metformin ≥ 6 months prior to screening Exclusion Criteria: History of Type 1 diabetes History of more than 1 episode of severe hypoglycemia within 6 months prior to screening, or a current diagnosis of hypoglycemia unawareness. Hospitalizations or Emergency room visits that would impact patient safety or data interpretation: Due to poor glucose control in the 6 months prior to screening or Any bariatric surgical procedures for weight loss. Significant change of body weight (>10%) in the 3 months before screening Proliferative retinopathy or maculopathy within the 6 months before screening or requiring acute treatment, or severe neuropathy

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: MLR-1023<br>* Each subject will receive an oral dose of placebo or MLR-1023 once before breakfast and either placebo (placebo and q.d. dose groups) or a second dose of MLR-1023 (b.i.d. dose groups) before dinner for 4 weeks.<br>|
| Active Comparator: 100 mg q.d.<br> | Drug: MLR-1023<br>* Each subject will receive an oral dose of placebo or MLR-1023 once before breakfast and either placebo (placebo and q.d. dose groups) or a second dose of MLR-1023 (b.i.d. dose groups) before dinner for 4 weeks.<br>|
| Active Comparator: 100 mg b.i.d.<br> | Drug: MLR-1023<br>* Each subject will receive an oral dose of placebo or MLR-1023 once before breakfast and either placebo (placebo and q.d. dose groups) or a second dose of MLR-1023 (b.i.d. dose groups) before dinner for 4 weeks.<br>|
| Active Comparator: 200 mg q.d.<br> | Drug: MLR-1023<br>* Each subject will receive an oral dose of placebo or MLR-1023 once before breakfast and either placebo (placebo and q.d. dose groups) or a second dose of MLR-1023 (b.i.d. dose groups) before dinner for 4 weeks.<br>|
| Active Comparator: 200 mg b.i.d.<br> | Drug: MLR-1023<br>* Each subject will receive an oral dose of placebo or MLR-1023 once before breakfast and either placebo (placebo and q.d. dose groups) or a second dose of MLR-1023 (b.i.d. dose groups) before dinner for 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PPG AUC0-3h in a MMTT between Days 1 and 29. |  | 29 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fasting plasma glucose in dose groups from Day 1 to Day 29, Day 36 |  | 36 Days | 
| Change in fructosamine level from Day 1 to Day 29 |  | 29 Days | 
| Change in fasting insulin from Day 1 to Day 29 |  | 29 Days | 
| Change in glycated albumin from Day 1 to Day 29 |  | 29 Days | 
| Change from Day 1 to Day 29 in insulin sensitivity using HOMA-R (HOMA-R = fasting plasma insulin (mU/l) * fasting plasma glucose (mmol/l) / 22.5) |  | 29 Days | 
| Changes from Day 1 to Day 29 in beta-cell function using HOMA-B (HOMA-B = 20 * fast- ￼ing plasma insulin (mU/l) / [fasting plasma glucose (mmol/l) - 3.5]) |  | 29 Days | 
| Change in HbA1C between Days 1 and Day 29 |  | 29 Days | 
| Changes in LDL-C, HDL-C, TG between Days 1 and Day 29 |  | 29 Days | 
| Change in weight between Days 1 and Day 29 |  | 29 Days | 
| Differences between placebo and MLR-1023 dose groups in PPG AUC0-3h Days 1 and 29. |  | 29 Days |