Ph 2a Study of HU6 on Energy Metabolism, Muscle and Liver Substrate Metabolism, and Mitochondrial Function in Subjects Who Are Overweight or Obese With Type 2 Diabetes

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled parallel group study of HU6 and placebo in subjects who are overweight or obese with T2D. The study will be conducted in 4 stages.

Detailed Description
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This is a randomized, double-blind, placebo-controlled parallel group study of HU6 and placebo in subjects who are overweight or obese with T2D. The study will be conducted in 4 stages (Figure 1). Stage 1: (screening) is conducted over a 29-day window (Day -48 to Day -20). Subjects who meet all of the eligibility criteria may proceed Stages 2 to 4 of the study. Stage 2 (baseline [pre-randomization]) is conducted over a 19-day period prior to randomization and includes a 13-day run-in and the first 6-day inpatient assessment period. At the end of Stage 2, subjects will be randomized 1:1 to HU6 or placebo. Stage 3 (double-blind dosing) is conducted after randomization. Day 1 is the first dose of double-blind study drug, and dosing continues over an approximate 26-week period. During this time, there will be study visits for safety, PK, and PD. Stage 3 of the study concludes with a 3-day run-in followed by the second 6-day inpatient assessment period. Stage 4 (washout) is conducted after dosing has ended and includes an approximate 4-week washout duration including a 3-day run-in followed by the third inpatient assessment period (3-day duration). The last day of the 3-day inpatient stay is the end-of-study. (Note that there will be a separate early termination visit for any subject who prematurely discontinues from the study

Official Title
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A 6-Month, Randomized, Double-Blind, Placebo-controlled, Phase 2a Study of the Effects of HU6 on Energy Metabolism, Muscle and Liver Substrate Metabolism, and Mitochondrial Function in Subjects Who Are Overweight or Obese With Type 2 Diabetes

Conditions
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Diabete Type 2, Obesity

Intervention / Treatment
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* Drug: HU6


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand the procedures and requirements of the study and provide written informed consent and authorization for protected health information disclosure. Willing and able to comply with the requirements of the study protocol. Male or female 18 to 70 years of age, inclusive, at time of informed consent. Body mass index (BMI) >28.0 kg/m2 and able to fit into the MRI machine. Subject has T2D meeting all of the following criteria: Exclusion Criteria: Body weight >450 pounds. Subject-reported history of weight gain or loss >5% in 3 months prior to screening. The subject participates in programmed exercise >3 hours per week.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment HU6<br>Subjects who are randomized to active study drug will receive 450mg of HU6 for 14 day and then 600mg of HU6 for 168 days. N = 24 | Drug: HU6<br>* HU6 is being evaluated for its effect on Energy Metabolism, Muscle and Liver Substrate Metabolism, and Mitochondrial Function<br>|
| Placebo Comparator: Placebo<br>Placebo Comparator is non-active study drug. N = 24 | Drug: HU6<br>* HU6 is being evaluated for its effect on Energy Metabolism, Muscle and Liver Substrate Metabolism, and Mitochondrial Function<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleeping Metabolic Rate (SMR) change from Baseline to 6 Months (26 weeks) | Change from baseline in SMR at 6 months (26 weeks) as assessed by whole room indirect calorimetry (WRIC). | 26 weeks |