Dose-Response Study to Evaluate the Effect of BKR-017 on Insulin Resistance and Other Metabolic Parameters in Type 2 Diabetes Patients

Study Overview
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Brief Summary
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This study is a randomized, double-blind, placebo-controlled, dose-response study of BKR-017 and placebo that will be conducted at two investigative sites. The total duration of subject involvement is approximately 15 weeks; the screening period can be up to 3 weeks prior to the start of test period, followed by a 12-week test period. During the test period, subjects will self-administer three tablets of test product, two times daily: before breakfast and before bedtime.

Official Title
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Randomized, Double-Blind, Placebo-Controlled, Dose-Response Study to Evaluate the Effect of BKR-017 on Insulin Resistance and Other Metabolic Parameters in Type 2 Diabetes Patients

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Dietary Supplement: BKR-017


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between the ages of 18 and 70 years at the time of screening, inclusive Diagnosed with T2D and under the care of a healthcare professional for its management, or newly diagnosed (as participant in the study) with T2D HbA1c 6.5% -10.5%, inclusive Has given written informed consent to participate in this study Willing to complete 84-day test period Willing to maintain current diet and exercise routine and current prescription medications for the duration of the study Exclusion Criteria: Type 1 diabetes History of bariatric or intestinal surgery Active gastrointestinal disease including but not limited to irritable bowel syndrome, inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis), diverticulitis, gastroparesis Active and clinically significant hepatic, pancreatic disease, or renal disease as determined by the investigator History of heart disease that in the opinion of the investigator should exclude the subject from the study Severely uncontrolled hypertension at screening defined as a systolic blood pressure > 180 mmHg or a diastolic blood pressure > 110 mmHg on the average of two seated measurements after being at rest for at least 5 minutes Untreated or uncontrolled hyperthyroidism or hypothyroidism, or other significant thyroid disease Active significant infection as determined by the investigator Known allergy to butyrate or any of the components of the tablets Subjects planning to make major changes to diet and physical activity during the trial duration Participation in a clinical trial and/or treatment with an investigational drug during the 30 days before screening, or within 5 half-lives of receipt of an investigational drug or twice the duration of the biological effect of any investigational drug (whichever is longer) Pregnant, nursing, or trying to become pregnant In the investigator's judgment, the subject is not suitable for the study for any other reason or cannot commit to the requirements of the study. Subject is taking one or more of the excluded therapies.

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Test Group 1<br>Group 1 will receive 84 days of placebo BID | Dietary Supplement: BKR-017<br>* Nutrient butyrate into a colon-targeted tablet formulation (BKR-017) is intended to stimulate secretion of GLP-1 from L-cells in the lower gut. Butyrate delivered to the colon in tablet form will not cause the side-effects seen with formation of butyrate by fermentation.<br>* Other names: Butyrate;|
| Active Comparator: Test Group 2<br>Group 2 will receive 84 days of 0.5 g of BKR-017 BID | Dietary Supplement: BKR-017<br>* Nutrient butyrate into a colon-targeted tablet formulation (BKR-017) is intended to stimulate secretion of GLP-1 from L-cells in the lower gut. Butyrate delivered to the colon in tablet form will not cause the side-effects seen with formation of butyrate by fermentation.<br>* Other names: Butyrate;|
| Active Comparator: Test Group 3<br>Group 3 will receive 84 days of 1.0 g of BKR-017 BID | Dietary Supplement: BKR-017<br>* Nutrient butyrate into a colon-targeted tablet formulation (BKR-017) is intended to stimulate secretion of GLP-1 from L-cells in the lower gut. Butyrate delivered to the colon in tablet form will not cause the side-effects seen with formation of butyrate by fermentation.<br>* Other names: Butyrate;|
| Active Comparator: Test Group 4<br>Group 4 will receive 84 days of 1.5 g of BKR-017 BID | Dietary Supplement: BKR-017<br>* Nutrient butyrate into a colon-targeted tablet formulation (BKR-017) is intended to stimulate secretion of GLP-1 from L-cells in the lower gut. Butyrate delivered to the colon in tablet form will not cause the side-effects seen with formation of butyrate by fermentation.<br>* Other names: Butyrate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in HOMA-IR | Changes in HOMA-IR at Days 21, 42, 63, and 84 using repeated measures ANCOVA | Baseline, Day 1, during the treatment period at days 21, 42, and 63, and at end of treatment period, Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in fasting low-density lipoprotein-cholesterol (LDL-C) | Changes in fasting low-density lipoprotein-cholesterol (LDL-C) at Days 1, 42, and 84 | Baseline, Day 1, during the treatment period at day 42, and at end of treatment period, Day 84 | 
| Changes in fasting triglycerides | Changes in fasting triglycerides at Days 1, 42, and 84 | Baseline, Day 1, during the treatment period at days 42, and at end of treatment period, Day 84 | 
| Changes in HbA1c | Changes in HbA1c at Days 1, 42, and 84 | Baseline, Day 1, during the treatment period at day 42, and at end of treatment period, Day 84 | 
| Changes in fasting glucose | Changes in fasting glucose at Days 1, 42, and 84 | Baseline, Day 1, during the treatment period at day 42, and at end of treatment period, Day 84 | 
| Changes in fasting insulin | Changes in fasting insulin at Days 1, 42, and 84 | Baseline, Day 1, during the treatment period at day 42, and at end of treatment period, Day 84 |