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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: KD026; Drug: Metformin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
  • California
    • Los Angeles, California, United States, 90036
      • Axis Clinical Trials
    • Los Angeles, California, United States, 90057
      • National Research Institute
    • West Hills, California, United States, 91307
      • Infosphere Clinical Research, Inc
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • Miami, Florida, United States, 33186
      • Med Research of Florida, LLC
  • North Carolina
    • High Point, North Carolina, United States, 27265
      • High Point Clinical Trials Center
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Texas
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Clinical Research Associates of Tidewater

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Response Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: April 28, 2015
• First Submitted That Met QC Criteria: April 30, 2015
• First Posted (Estimated): May 5, 2015

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: April 1, 2023

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; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: KD026-201