A Study to Evaluate the Pharmacodynamic Effects of Single-Dose Co-Administration of LX4211 With Januvia® in Type 2 Diabetics

A Phase 1, Open-label, 3-period, 3-treatment, Single Dose Crossover Study to Evaluate the Pharmacodynamic Effects of LX4211 When Administered Concurrently With JANUVIA® (Sitagliptin) in Subjects With Type 2 Diabetes Mellitus

This study is intended to evaluate the pharmacodynamics, safety, and tolerability of LX4211 when administered concurrently with sitagliptin (Januvia®) in patients with Type 2 Diabetes Mellitus.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: LX4211; Drug: Januvia®

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78209
      • Lexicon Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged 18 to 65 years of age
• History of Type 2 Diabetes Mellitus for at least 3 months prior to Screening, with HgbA1c values of 6.5 to 10.5% and C-peptide ≥1.0 ng/mL
• Body mass index (BMI) ≤45 kg/sq m
• Willing and able to self-monitor blood glucose
• Able to provide written informed consent

Exclusion Criteria:

• History of Type 1 diabetes mellitus, diabetic ketoacidosis, hyperosmolar nonketotic syndrome, or diabetes resulting from pancreatic disorder or secondary diabetes
• Current use of any blood glucose lowering agent other than metformin
• History of renal disease or clinically significant abnormal kidney function tests at Screening or Day -2
• Presence of active hepatic disease or clinically significant abnormal liver function tests at Screening or Day -2
• History of myocardial infarction, severe/unstable angina, or coronary revascularization procedure within 6 months of Day -2
• History of clinically significant cardiac arrhythmias within 1 year of Day -2
• Congestive heart failure and/or New York Heart Association (NYHA) class III or IV symptoms of heart failure
• Subjects with uncontrolled Stage 3 hypertension
• History of 2 or more emergency room visits, doctor's visits, or hospitalizations due to hypoglycemia within 6 months of Day -2
• History of alcohol or drug abuse within 12 months of Screening
• History of bowel resection > 20 cm, any malabsorptive disorder, severe gastroparesis, and GI procedure for the purpose of weight loss that would slow gastric emptying
• History of HIV or hepatitis C
• Major surgery within 3 months of Day -2 or any planned surgery during the study
• History of any active infection within 2 weeks of Day -2
• History of pancreatitis
• History of any malignancy within the last 5 years which would affect the diagnosis or assessment of LX4211 or sitagliptin
• History of any serious adverse reaction or hypersensitivity to LX4211 or sitagliptin
• Presence of any clinically significant physical, laboratory, or ECG findings or any concurrent condition at Screening that may interfere with the study in the opinion of the investigator
• Triglycerides > 1000 mg/dL at Screening or Day -2
• Donation or loss of >400 mL of blood or blood product within 8 weeks prior to Day -2
• Use of any tobacco product for the duration of study participation
• Use of corticosteroids within 2 weeks of Day 1
• Use of digoxin or warfarin within 2 weeks prior to Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment C	Drug: LX4211; 400 mg of LX4211 administered as two 200 mg tablets; Drug: Januvia®; 100 mg Januvia® (sitagliptin) administered as one 100 mg sitagliptin tablet
Experimental: Treatment A	Drug: LX4211; 400 mg of LX4211 administered as two 200 mg tablets
Active Comparator: Treatment B	Drug: Januvia®; 100 mg Januvia® (sitagliptin) administered as one 100 mg sitagliptin tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in gut hormones	Days 1, 8, and 15

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in fasting plasma glucose	Days 1, 8, and 15
Change from baseline in postprandial glucose	Days 1, 8, and 15
Change from baseline in insulin	Days 1, 8, and 15
Change from baseline in peptide YY	Days 1, 8, and 15
Change from baseline in urinary glucose excretion	Days 1, 8, and 15

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals

Publications and helpful links

General Publications

• Zambrowicz B, Ding ZM, Ogbaa I, Frazier K, Banks P, Turnage A, Freiman J, Smith M, Ruff D, Sands A, Powell D. Effects of LX4211, a dual SGLT1/SGLT2 inhibitor, plus sitagliptin on postprandial active GLP-1 and glycemic control in type 2 diabetes. Clin Ther. 2013 Mar;35(3):273-285.e7. doi: 10.1016/j.clinthera.2013.01.010. Epub 2013 Feb 21.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: September 23, 2011
• First Submitted That Met QC Criteria: September 26, 2011
• First Posted (Estimate): September 27, 2011

Study Record Updates

• Last Update Posted (Estimate): January 31, 2012
• Last Update Submitted That Met QC Criteria: January 26, 2012
• Last Verified: January 1, 2012

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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate; (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: LX4211.1-105-DM; LX4211.105 (Other Identifier: Lexicon Pharmaceuticals, Inc.)