Safety and Efficacy of LX4211 With Metformin in Type 2 Diabetes Patients With Inadequate Glycemic Control on Metformin

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of LX4211 in Combination With Metformin in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Monotherapy

This study is intended to assess the effect on HbA1c of different dose regimens of LX4211 in combination with metformin in subjects with Type 2 Diabetes Mellitus who have inadequate glycemic control on metformin monotherapy.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: 75 mg LX4211; Drug: 200 mg LX4211; Drug: 200 mg LX4211; Drug: 400 mg LX4211; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 299
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Lexicon Investigational Site
    • Carmichael, California, United States, 95608
      • Lexicon Investigational Site
    • Greenbrae, California, United States, 94904
      • Lexicon Investigational Site
    • La Jolla, California, United States, 92037
      • Lexicon Investigational Site
    • Northridge, California, United States, 91325
      • Lexicon Investigational Site
    • Orange, California, United States, 92868
      • Lexicon Investigational Site
    • Pismo Beach, California, United States, 93449
      • Lexicon Investigational Site
    • Tarzana, California, United States, 91356
      • Lexicon Investigational Site
    • Tustin, California, United States, 92780
      • Lexicon Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80209
      • Lexicon Investigational Site
    • Denver, Colorado, United States, 80220
      • Lexicon Investigational Site
  • Delaware
    • Newark, Delaware, United States, 19713
      • Lexicon Investigational Site
  • Florida
    • Edgewater, Florida, United States, 32132
      • Lexicon Investigational Site
    • Miami, Florida, United States, 33135
      • Lexicon Investigational Site
    • Orlando, Florida, United States, 32806
      • Lexicon Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • Lexicon Investigational Site
    • Winter Park, Florida, United States, 32792
      • Lexicon Investigational Site
  • Georgia
    • Blue Ridge, Georgia, United States, 30513
      • Lexicon Investigational Site
    • Savannah, Georgia, United States, 31406
      • Lexicon Investigational Site
  • Indiana
    • Lafayette, Indiana, United States, 47904
      • Lexicon Investigational Site
  • Kentucky
    • Madisonville, Kentucky, United States, 42431
      • Lexicon Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Lexicon Investigational Site
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
      • Lexicon Investigational Site
    • Waltham, Massachusetts, United States, 02453
      • Lexicon Investigational Site
  • Michigan
    • Traverse City, Michigan, United States, 49684
      • Lexicon Investigational Site
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
      • Lexicon Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Lexicon Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Lexicon Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89101
      • Lexicon Investigational Site
    • Las Vegas, Nevada, United States, 89128
      • Lexicon Investigational Site
  • New York
    • Great Neck, New York, United States, 11023
      • Lexicon Investigational Site
    • West Seneca, New York, United States, 14224
      • Lexicon Investigational Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27455
      • Lexicon Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • Lexicon Investigational Site
  • North Dakota
    • Grand Forks, North Dakota, United States, 58201
      • Lexicon Investigational Site
  • Ohio
    • Canal Fulton, Ohio, United States, 44614
      • Lexicon Investigational Site
    • Dayton, Ohio, United States, 45439
      • Lexicon Investigational Site
    • Kettering, Ohio, United States, 45429
      • Lexicon Investigational Site
    • Perrysburg, Ohio, United States, 43551
      • Lexicon Investigational Site
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Lexicon Investigational Site
  • Pennsylvania
    • Uniontown, Pennsylvania, United States, 15401
      • Lexicon Investigational Site
  • South Carolina
    • Clinton, South Carolina, United States, 29325
      • Lexicon Investigational Site
    • Mt. Pleasant, South Carolina, United States, 29464
      • Lexicon Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • Lexicon Investigational Site
    • Chattanooga, Tennessee, United States, 37421
      • Lexicon Investigational Site
  • Texas
    • Austin, Texas, United States, 78728
      • Lexicon Investigational Site
    • Dallas, Texas, United States, 75230
      • Lexicon Investigational Site
    • Houston, Texas, United States, 77024
      • Lexicon Investigational Site
    • Houston, Texas, United States, 77098
      • Lexicon Investigational Site
    • Killeen, Texas, United States, 76543
      • Lexicon Investigational Site
    • San Antonio, Texas, United States, 78229
      • Lexicon Investigational Site
    • San Antonio, Texas, United States, 78258
      • Lexicon Investigational Site
    • Tomball, Texas, United States, 77375
      • Lexicon Investigational Site
  • Utah
    • Ogden, Utah, United States, 84403
      • Lexicon Investigational Site
    • Salt Lake City, Utah, United States, 84109
      • Lexicon Investigational Site
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Lexicon Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult subjects between the ages of 18 to 75 years, inclusive
• Confirmed diagnosis of Type 2 diabetes mellitus
• Meet required laboratory values at screening, including fasting plasma glucose less than 270 mg/dL
• Stable dose of metformin monotherapy greater than 1500 mg/day for at least 8 weeks
• Willing and able to provide written informed consent
• Willing and able to maintain consistent dietary, physical activity, and sleeping patterns throughout the study

Exclusion Criteria:

• History of Type 1 diabetes mellitus, diabetic ketoacidosis, hyperosmolar nonketotic syndrome, or diabetes resulting from pancreatic disorder or secondary diabetes
• History of renal disease or clinically significant abnormal kidney function tests
• Presence of active hepatic disease or clinically significant abnormal liver function tests
• Subjects with a history of heart attack, severe/unstable angina, or coronary revascularization procedure within 6 months prior to study Day 1
• History of clinically significant cardiac arrhythmias within one year of study Day 1
• Subjects with congestive heart failure
• Subjects with uncontrolled Stage III hypertension
• Triglycerides >1000 mg/dL at Screening
• Known history of HIV or hepatitis C
• History of illicit drug or alcohol abuse with one year of study Day 1
• Have had 2 or more emergency room visits, doctor visits, or hospitalizations due to hypoglycemia within 6 months of study Day 1
• Use of any other investigational drug within 30 days of study Day 1
• Prior exposure to LX4211
• Use of any medication or herbal supplement for the purpose of weight loss
• Chronic use of any antidiabetic therapy other than metformin in the 3 months prior to study Day 1
• Use of corticosteroids within 2 weeks prior to study Day 1
• Major surgery within 6 months of study Day 1
• Subjects with any history of severe gastroparesis
• Inability or difficulty swallowing whole capsules or tablets
• Women who are pregnant or breast feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Subjects will receive placebo once daily.
EXPERIMENTAL: Treatment B	Drug: 200 mg LX4211; Subjects will receive 200 mg LX4211 once daily.; Drug: 200 mg LX4211; Subjects will receive 200 mg LX4211 twice daily.
EXPERIMENTAL: Treatment C	Drug: 400 mg LX4211; Subjects will receive 400 mg LX4211 once daily.
EXPERIMENTAL: Treatment A	Drug: 75 mg LX4211; Subjects will receive 75 mg LX4211 once daily
EXPERIMENTAL: Treatment D	Drug: 200 mg LX4211; Subjects will receive 200 mg LX4211 once daily.; Drug: 200 mg LX4211; Subjects will receive 200 mg LX4211 twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in HbA1c to Week 12	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Achieving a HbA1c Value of <7% at Week 12	12 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12	12 weeks
Change From Baseline in Body Weight at Week 12	12 weeks
Change From Baseline in Systolic Blood Pressure (SPB) at Week 12	12 weeks
Change From Baseline in Triglycerides at Week 12	12 weeks

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals

Publications and helpful links

General Publications

• Rosenstock J, Cefalu WT, Lapuerta P, Zambrowicz B, Ogbaa I, Banks P, Sands A. Greater dose-ranging effects on A1C levels than on glucosuria with LX4211, a dual inhibitor of SGLT1 and SGLT2, in patients with type 2 diabetes on metformin monotherapy. Diabetes Care. 2015 Mar;38(3):431-8. doi: 10.2337/dc14-0890. Epub 2014 Sep 11.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ACTUAL): May 1, 2012
• Study Completion (ACTUAL): May 1, 2012

Study Registration Dates

• First Submitted: June 16, 2011
• First Submitted That Met QC Criteria: June 17, 2011
• First Posted (ESTIMATE): June 20, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): October 31, 2014
• Last Update Submitted That Met QC Criteria: October 29, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: diabetes mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
• Other Study ID Numbers: LX4211.1-202-DM; LX4211.202 (OTHER: Lexicon Pharmaceuticals, Inc.)