Adult Subjects With Uncontrolled Type 2 Diabetes

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

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: MLR-1023

Detailed Description

Objectives

1. To assess the safety, tolerability and initial anti-diabetic activity of MLR-1023 in subjects with uncontrolled mild to moderate type 2 diabetes mellitus
2. 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.

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • USA and South Korea, Pennsylvania, United States
      • Melior Pharmaceuticals I & Bukwang Pharm. Co., Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosed with uncontrolled T2DM who have received diet and exercise therapy for at least 3 months prior to screening, aged ≥ 18 - ≤ 75 years
2. Females must be post-menopausal, unable to conceive, or test negative for pregnancy via blood test and use barrier contraception
3. BMI ranging from ≥ 20 to ≤ 40 kg/m2
4. Fasting plasma glucose values of up to 240 mg/dL at screening, after wash-out (visit 2) and after placebo run-in (visit 3)
5. (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:

1. History of Type 1 diabetes
2. History of more than 1 episode of severe hypoglycemia within 6 months prior to screening, or a current diagnosis of hypoglycemia unawareness.

3. Hospitalizations or Emergency room visits that would impact patient safety or data interpretation:

   1. Due to poor glucose control in the 6 months prior to screening or
   2. Any bariatric surgical procedures for weight loss.
4. Significant change of body weight (>10%) in the 3 months before screening
5. Proliferative retinopathy or maculopathy within the 6 months before screening or requiring acute treatment, or severe neuropathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: MLR-1023; 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.
Active Comparator: 100 mg q.d.	Drug: MLR-1023; 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.
Active Comparator: 100 mg b.i.d.	Drug: MLR-1023; 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.
Active Comparator: 200 mg q.d.	Drug: MLR-1023; 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.
Active Comparator: 200 mg b.i.d.	Drug: MLR-1023; 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Melior Pharmaceuticals
• Collaborators: Bukwang Pharmaceutical, Co., Ltd.
• Investigators: Study Director: Melior Pharmaceuticals I & Bukwang Pharm. Co., Ltd., Melior Pharmaceuticals I & Bukwang Pharm. Co., Ltd.

Publications and helpful links

General Publications

• Lee MK, Kim SG, Watkins E, Moon MK, Rhee SY, Frias JP, Chung CH, Lee SH, Block B, Cha BS, Park HK, Kim BJ, Greenway F. A novel non-PPARgamma insulin sensitizer: MLR-1023 clinicalproof-of-concept in type 2 diabetes mellitus. J Diabetes Complications. 2020 May;34(5):107555. doi: 10.1016/j.jdiacomp.2020.107555. Epub 2020 Feb 2.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: December 11, 2014
• First Submitted That Met QC Criteria: December 15, 2014
• First Posted (Estimate): December 16, 2014

Study Record Updates

• Last Update Posted (Estimate): September 26, 2016
• Last Update Submitted That Met QC Criteria: September 23, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: BK-MD-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Undecided