Study of Two Oral Formulations of LX4211 in Patients With Type 2 Diabetes Mellitus

A Phase 1, Randomized, Open-Label, Three-Way Crossover Study of Two Oral Formulations of LX4211 in Subjects With Type 2 Diabetes Mellitus

This protocol is intended to compare the effects of both a solid (tablet) and liquid oral dosage form of LX4211 in subjects with type 2 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: 300 mg LX4211 (150 mg tablets); Drug: 300 mg LX4211 (50 mg tablets); Drug: 300 mg LX4211 (liquid)

• Study Type: Interventional
• Enrollment (Anticipated): 15
• 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
• Males and females of non-childbearing potential
• Diagnosis of type 2 diabetes mellitus for at least 6 months prior to screening
• Fasting plasma glucose ≤240 mg/dL
• Body mass index <42 kg/sq m
• HbA1c of 7-11%
• C-peptide of ≥1.0 ng/mL
• Ability to provide written informed consent

Exclusion Criteria:

• History of type 1 diabetes mellitus, diabetic ketoacidosis, hyperosmolar nonketonic syndrome, incontinence, or nocturia
• Current use of any blood glucose-lowering agent other than metformin
• Exposure to insulin, thiazide, or loop diuretics within 4 weeks prior to screening
• History of HIV, Hepatitis B, or Hepatitis C
• Surgery within 6 months of screening
• Donation or loss of >400 mL of blood or blood product within 8 weeks prior to start of study
• Use of proteins or antibodies within 12 weeks prior to screening. (Flu shots are allowed.)
• Exposure to any investigational agent or participation in an investigational trial within 30 days of the start of the study
• History of drug or alcohol abuse within 12 months 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: Solid Oral Dose - 150 mg tablets	Drug: 300 mg LX4211 (150 mg tablets); Single oral dose of two 150 mg tablets LX4211
Experimental: Solid Oral Dose - 50 mg tablets	Drug: 300 mg LX4211 (50 mg tablets); Single oral dose of six 50 mg tablets LX4211
Experimental: Liquid Oral Dose	Drug: 300 mg LX4211 (liquid); Single 30 mL dose of liquid oral solution LX4211 (10 mg/mL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed plasma concentration	Pharmacokinetics samples collected on day of dosing and 24 and 48 hours post-dose (Follow-up).
Time at which maximum observed plasma concentration occurs	Pharmacokinetics samples collected on day of dosing and 24 and 48 hours post-dose (Follow-up).
Half-life of the drug in plasma	Pharmacokinetics samples collected on day of dosing and 24 and 48 hours post-dose (Follow-up).

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma glucose	Samples collected on initial visit; Day -15 and Day -5 (Washout); numerous timepoints on Day -1 (Washout) and day of dosing; 24 hours post-dose (Follow-up); and upon discharge.
Urinary glucose excretion	Samples collected on Day -1 (Washout), day of dosing, and 24 and 48 hours post-dose (Follow-up).
Insulin	Samples collected on initial visit; Day -15 and Day -5 (Washout); numerous timepoints on Day -1 (Washout) and day of dosing; 24 hours post-dose (Follow-up); and upon discharge.
Peptide YY	Samples collected on initial visit; Day -15 and Day -5 (Washout); numerous timepoints on Day -1 (Washout) and day of dosing; 24 hours post-dose (Follow-up); and upon discharge.
Glucagon-like Peptide 1	Samples collected on initial visit; Day -15 and Day -5 (Washout); numerous timepoints on Day -1 (Washout) and day of dosing; 24 hours post-dose (Follow-up); and upon discharge.

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Investigators: Study Director: Joel P. Freiman, MD, MPH, Lexicon Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Zambrowicz B, Freiman J, Brown PM, Frazier KS, Turnage A, Bronner J, Ruff D, Shadoan M, Banks P, Mseeh F, Rawlins DB, Goodwin NC, Mabon R, Harrison BA, Wilson A, Sands A, Powell DR. LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin Pharmacol Ther. 2012 Aug;92(2):158-69. doi: 10.1038/clpt.2012.58. Epub 2012 Jul 4.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: August 24, 2010
• First Submitted That Met QC Criteria: August 24, 2010
• First Posted (Estimate): August 26, 2010

Study Record Updates

• Last Update Posted (Estimate): March 30, 2011
• Last Update Submitted That Met QC Criteria: March 29, 2011
• Last Verified: March 1, 2011

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; 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: LX4211.1-102-DM; LX4211.102 (Other Identifier: Lexicon Pharmaceuticals, Inc.)