Study to Evaluate the Pharmacodynamic and Pharmacokinetic Effects of LX4211 in Subjects With Type 2 Diabetes and Renal Impairment

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Parallel Group Study to Evaluate the Pharmacodynamic and Pharmacokinetic Effects of LX4211 in Subjects With Type 2 Diabetes Mellitus and Moderate to Severe Renal Impairment

This Phase 1 study is intended to assess the pharmacodynamics (PD), pharmacokinetics (PK), safety and tolerability of LX4211 following once daily oral administration in subjects with type 2 diabetes mellitus (T2DM) and moderate to severe renal impairment.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Renal Impairment
• Intervention / Treatment: Drug: LX4211; Drug: LX4211 Placebo

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Lexicon Investigational Site
  • California
    • Chula Vista, California, United States, 91911
      • Lexicon Investigational Site
  • Florida
    • Edgewater, Florida, United States, 32132
      • Lexicon Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Lexicon Investigational Site
  • Texas
    • San Antonio, Texas, United States, 78209
      • Lexicon Investigational Site
  • Washington
    • Renton, Washington, United States, 98057
      • Lexicon Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults ≥18 to ≤80 years of age
• History of T2DM for at least 6 months prior to screening
• Moderate to severe renal impairment and not actively on dialysis
• Willing and able to perform self-monitoring of blood glucose
• Willing and able to provide written informed consent

Exclusion Criteria:

• History of type 1 diabetes mellitus, diabetic ketoacidosis (within the previous 6 months), or diabetes resulting from pancreatic disorder or secondary diabetes (from acromegaly and/or Cushing's disease)
• Subjects who have received a renal allograft
• Subjects expecting to require dialysis or to undergo kidney transplantation within 3 months of study dosing
• Presence of active hepatic disease or clinically significant abnormal liver function tests at Screening or planned study Day -1
• Subjects with a history of heart attack, severe/unstable angina, or coronary revascularization procedure within 6 months prior to study Day -2
• History of clinically significant cardiac arrhythmias within 1 year prior to study Day -2
• Subjects with congestive heart failure
• Subjects with uncontrolled Stage III hypertension
• History of 2 or more emergency room visits, doctors' visits, or hospitalizations due to hypoglycemia within the 6 months prior to planned study Day -2
• History of alcohol or illicit drug abuse within 1 year prior to Screening
• History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Major surgery within 6 months prior to planned study Day -2
• History of any malignancy within the last 5 years
• Triglycerides >1000 mg/dL at Screening or planned study Day -1
• History of any serious adverse reaction or hypersensitivity to an SGLT inhibitor
• Use of corticosteroids within 2 weeks prior to study Day 1
• Use of any investigational drug within 30 days prior to study Day 1, or investigational protein or antibodies within 60 days of Day 1
• Positive urine pregnancy test at Screening
• Positive urine screen for illicit drug abuse at Screening
• Prior exposure to LX4211

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A	Drug: LX4211; Subjects will receive LX4211 once daily for 7 days
Placebo Comparator: LX4211 Placebo	Drug: LX4211 Placebo; Subjects will receive LX4211 placebo once daily for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in postprandial glucose	baseline to 7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects experiencing an adverse event	7 days
Change from baseline in fasting plasma glucose	baseline to 7 days
Change from baseline in glucagon-like peptide 1 (Glp-1)	baseline to 7 days
Area Under Curve (AUC)	Days 1 and 7; predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Investigators: Study Director: Ike Ogbaa, M.D., Lexicon Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Zambrowicz B, Lapuerta P, Strumph P, Banks P, Wilson A, Ogbaa I, Sands A, Powell D. LX4211 therapy reduces postprandial glucose levels in patients with type 2 diabetes mellitus and renal impairment despite low urinary glucose excretion. Clin Ther. 2015 Jan 1;37(1):71-82.e12. doi: 10.1016/j.clinthera.2014.10.026. Epub 2014 Dec 17.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: March 7, 2012
• First Submitted That Met QC Criteria: March 13, 2012
• First Posted (Estimate): March 15, 2012

Study Record Updates

• Last Update Posted (Estimate): September 9, 2013
• Last Update Submitted That Met QC Criteria: September 6, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Renal Insufficiency; 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: LX4211.1-107-DM; LX4211.107 (Other Identifier: Lexicon Pharmaceuticals, Inc.)