Clinical trial NCT02317796: Adult Subjects With Uncontrolled Type 2 Diabetes
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes
Lead sponsor: Melior Pharmaceuticals
Sponsor class: OTHER
Collaborators: name: Bukwang Pharmaceutical, Co., Ltd.
First posted: 2014-12-16
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in PPG AUC0-3h in a MMTT between Days 1 and 29.
timeFrame: 29 Days
Secondary outcomes:
measure: Change in fasting plasma glucose in dose groups from Day 1 to Day 29, Day 36
timeFrame: 36 Days
measure: Change in fructosamine level from Day 1 to Day 29
timeFrame: 29 Days
measure: Change in fasting insulin from Day 1 to Day 29
timeFrame: 29 Days
measure: Change in glycated albumin from Day 1 to Day 29
timeFrame: 29 Days
measure: 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)
timeFrame: 29 Days
measure: 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])
timeFrame: 29 Days
measure: Change in HbA1C between Days 1 and Day 29
timeFrame: 29 Days
measure: Changes in LDL-C, HDL-C, TG between Days 1 and Day 29
timeFrame: 29 Days
measure: Change in weight between Days 1 and Day 29
timeFrame: 29 Days
measure: Differences between placebo and MLR-1023 dose groups in PPG AUC0-3h Days 1 and 29.
timeFrame: 29 Days
Other outcomes:
Locations:
city: USA and South Korea
country: United States
facility: Melior Pharmaceuticals I & Bukwang Pharm. Co., Ltd.
state: Pennsylvania
Study officials:
affiliation: Melior Pharmaceuticals I & Bukwang Pharm. Co., Ltd.
name: Melior Pharmaceuticals I & Bukwang Pharm. Co., Ltd.
role: STUDY_DIRECTOR
References:
citation: 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.