Study of KD026 in Combination With Metformin in Subjects With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This study will compare the safety, tolerability and efficacy of the combination of KD026 and metformin compared to placebo and metformin on improving glycemic control in patients with type 2 diabetes mellitus.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of KD026 in Combination With Metformin in Subjects With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: KD026
* Drug: Placebo
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have type 2 diabetes, with finger stick HbA1c ≥ 7.0% and ≤ 11.0% at screening visit, and HbA1c via venipuncture ≥ 7.0% and ≤ 11.0 % at the Qualification visit Have been on metformin for at least 12 weeks prior to screening visit and the metformin dose is not expected to change during the 4-week run-in period Have a BMI of ≥ 27 kg/m2 and ≤ 45 kg/m2 Men, post-menopausal women (defined as not having a menstrual period for at least 1 year), surgically sterile women (for at least 1 year), or women of childbearing potential with a negative pregnancy test within the last 24 hours Women of childbearing potential and men whose partners are of childbearing potential must agree to use two forms of accepted methods of contraception during the course of the study and for 1 month after their last dose of study drug. Effective birth control includes (a) IUD plus one barrier method; (b) on stable doses of hormonal contraception for at least 3 months (eg, oral, injectable, implant, transdermal) plus one barrier method; (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); or (d) a vasectomized partner Exclusion Criteria: Have type 1 diabetes Taking antidiabetic medications other than or in addition to metformin Have fasting plasma glucose > 270 mg/dL at screening visit Have a serum creatinine ≥1.7 mg/dL or glomerular filtration rate <60 mL/min at screening visit Have a history of diabetic retinopathy Uncontrolled high blood pressure Have a history of chronic liver disease and/or alanine transaminase (ALT) or aspartate transaminase (AST) >2.0 × the upper limit of normal (ULN) at screening visit. Have a history of a malignant cancer (other than basal cell, localized cervical, or squamous cell carcinoma of the skin that has been removed) Have a history or presence of gastrointestinal (GI) disease or major gastrointestinal surgery that, in the opinion of the investigator, could interfere with drug absorption Currently using any of prohibited medications that cannot be stopped Abuse alcohol (defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units [1 unit is equivalent to a half pint of beer, 1 serving of hard liquor, or one glass of wine] History or presence of drug abuse according to Diagnostic and Statistical Manual of Mental Disorders V (DSM-V) criteria within the 2 years prior to screening visit Have a 12-lead ECG at screening visit that, in the opinion of the investigator, have abnormalities that may compromise safety in this study, including a QTc(F) interval (QT interval data corrected using Fridericia's formula) of > 450 msec Have a clinically significant abnormal laboratory result including thyroid-stimulating hormone (TSH) >1.5 × ULN at screening visit Have a positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody/virus (HCV) or human immunodeficiency virus (HIV) antibodies at screening visit or a documented history of a positive result Pregnant or lactating woman Previously received KD026 (formerly named SLx-4090) Participated in a trial with any investigational drug within 4 weeks prior to screening visit

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 100 mg KD026 BID<br>100 mg KD026 twice a day (BID) in combination with Metformin for 12 weeks | Drug: KD026<br>* Dosed in combination<br>* Other names: SLx-4090;Drug: Metformin<br>* Drug prescribed by each subject's prescribing physician<br>|
| Experimental: Cohort 2 150 mg KD026 BID<br>150 mg KD026 BID in combination with Metformin for 12 weeks | Drug: KD026<br>* Dosed in combination<br>* Other names: SLx-4090;Drug: Metformin<br>* Drug prescribed by each subject's prescribing physician<br>|
| Experimental: Cohort 3 200 mg KD026 BID<br>200 mg KD026 BID in combination with Metformin for 12 weeks | Drug: KD026<br>* Dosed in combination<br>* Other names: SLx-4090;Drug: Metformin<br>* Drug prescribed by each subject's prescribing physician<br>|
| Experimental: Cohort 4 100 mg KD026 TID<br>100 mg KD026 three times a day (TID) in combination with Metformin for 12 weeks | Drug: KD026<br>* Dosed in combination<br>* Other names: SLx-4090;Drug: Metformin<br>* Drug prescribed by each subject's prescribing physician<br>|
| Placebo Comparator: Cohort 1 Placebo<br>Matched Placebo Dose BID in combination with Metformin for 12 weeks | Drug: Placebo<br>* Dosed in combination<br>Drug: Metformin<br>* Drug prescribed by each subject's prescribing physician<br>|
| Placebo Comparator: Cohort 2 Placebo<br>Matched Placebo Dose BID in combination with Metformin for 12 weeks | Drug: Placebo<br>* Dosed in combination<br>Drug: Metformin<br>* Drug prescribed by each subject's prescribing physician<br>|
| Placebo Comparator: Cohort 3 Placebo<br>Matched Placebo Dose BID in combination with Metformin for 12 weeks | Drug: Placebo<br>* Dosed in combination<br>Drug: Metformin<br>* Drug prescribed by each subject's prescribing physician<br>|
| Placebo Comparator: Cohort 4 Placebo<br>Matched Placebo Dose TID in combination with Metformin for 12 weeks | Drug: Placebo<br>* Dosed in combination<br>Drug: Metformin<br>* Drug prescribed by each subject's prescribing physician<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Experiencing Adverse Events as a Measure of Safety, Tolerability, and Efficacy | To assess the safety, tolerability, and efficacy (as measured by a 0.5%-1.5% decrease of HbA1c) of different dosages and dosing regimens of a combination of KD026 and metformin compared to placebo and metformin when administered for 3 months to subjects with type 2 diabetes mellitus | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Fasting Plasma Glucose (FPG) | To assess changes in fasting plasma glucose from baseline to Week 12 | 12 Weeks | 
| Changes in Insulin | To assess changes in insulin from baseline to Week 12 | 12 Weeks | 
| Changes in HOMA-IR | To assess changes in Homeostasis Model Assessment - Insulin Resistance (HOMA-IR) from baseline to Week 12 | 12 Weeks | 
| Changes in Body Weight | To assess changes in body weight | 12 Weeks | 
| Changes in AUC | To assess the 6-hour time curve (AUC) for post prandial triglycerides and glucose. | 12 Weeks | 
| Changes in Lipids | To assess changes in total cholesterol, LDL-C, HDL-C, non-HDL-C, VLDL-C, and triglyceride levels | 12 Weeks | 
| Changes in Blood Pressure | To assess changes, if any, in baseline blood pressure associated with metabolic syndrome | 12 Weeks | 
| Changes in Waist Circumference | To assess changes, if any, in baseline waist circumference associated with metabolic syndrome | 12 Weeks | 
| Changes in Body Mass Index (BMI) | To assess changes, if any, in baseline measures of BMI associated with metabolic syndrome | 12 Weeks | 
| Changes in Plasma Levels of KD026 | To assess plasma levels of KD026 in all subjects | 12 Weeks | 
| Changes in Serum Levels of Non-Esterified Free Fatty Acids | To assess the change in serum levels of non-esterified free fatty acids from baseline to Week 12 | 12 Weeks |