A Study to Determine the Pharmacodynamics of LX4211 Relative to Meals in Healthy Subjects

A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Study to Determine the Pharmacodynamics of LX4211 Relative to Meals in Healthy Subjects

The primary purpose of this study is to evaluate the pharmacodynamics of LX4211 relative to meals in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Schedule A; Drug: Schedule B; Drug: Schedule C; Drug: Schedule D; Drug: Schedule E

• Study Type: Interventional
• Enrollment (Anticipated): 14
• 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 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults ≥18 and ≤55 years of age
• Vital signs at Screening in the following ranges: systolic blood pressure, 90-140 mm Hg; diastolic blood pressure, 50-90 mm Hg; heart rate, 50-100 bpm
• Body mass index (BMI) ≥18 and ≤35 kg/sq m
• Able to provide written informed consent

Exclusion Criteria:

• Use of any medication (prescription, over-the-counter, herbal tea, or supplements) within 5 days of dosing
• Use of any investigational agent or study treatment within 30 days of Day 1
• Use of any protein or antibody-based therapeutic agents within 3 months of Screening
• Prior exposure to any SGLT inhibitor
• Use of cigarettes or any tobacco products within 6 weeks prior to Screening and while participating in the study
• History of bariatric surgery or any other gastrointestinal surgery that may induce malabsorption
• History of any major surgery within 6 months of Screening
• History of any hypersensitivity to the inactive components of LX4211
• History of renal disease or significantly abnormal kidney function tests
• History of hepatic disease or significantly abnormal liver function tests
• History of any active infection within 30 days of Day 1
• History of alcohol or substance abuse within 2 years prior to Day 1
• Positive urine glucose at Screening
• Positive pregnancy test at Screening
• Inability or difficulty swallowing whole tablets or capsules
• Unable or unwilling to communicate or cooperate with the Investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LX4211; 400 mg of LX4211 administered orally	Drug: Schedule A; Dosing 1 hour before breakfast; Drug: Schedule B; Dosing 0.5 hour before breakfast; Drug: Schedule C; Dosing immediately before breakfast; Drug: Schedule D; Dosing immediately before lunch; Drug: Schedule E; Split dose, dosing 1 hour before breakfast and dinner
PLACEBO_COMPARATOR: Placebo; Nonidentical placebo administered orally	Drug: Schedule A; Dosing 1 hour before breakfast; Drug: Schedule B; Dosing 0.5 hour before breakfast; Drug: Schedule C; Dosing immediately before breakfast; Drug: Schedule D; Dosing immediately before lunch; Drug: Schedule E; Split dose, dosing 1 hour before breakfast and dinner

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Urinary glucose excretion	24 hours collection on Day -1 and Days 7-13
Fasting Plasma Glucose	Day -1 and Days 7-12
Postprandial Glucose	Day -1 and Days 7-12
Insulin	Day -1 and Days 7-12
Glucagon-like peptide 1 (total and active)	Day -1 and Days 7-12
Peptide YY	Day -1 and Days 7-12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events		Day 1 to Day 14
Blood chemistry	Including albumin, ALP, ALT, AST, total bilirubin, glucose, BUN, calcium, carbon dioxide, chloride, cholesterol and triglycerides, creatinine, magnesium, phosphorus, potassium, sodium, protein, and uric acid.	Day -2, Day 7 and Day 13
Hematology	Including complete blood count with differential, hemoglobin, hematocrit, lymphocyte, and platelet counts.	Day -2, Day 7 and Day 13

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals

Publications and helpful links

General Publications

• Zambrowicz B, Ogbaa I, Frazier K, Banks P, Turnage A, Freiman J, Boehm KA, Ruff D, Powell D, Sands A. Effects of LX4211, a dual sodium-dependent glucose cotransporters 1 and 2 inhibitor, on postprandial glucose, insulin, glucagon-like peptide 1, and peptide tyrosine tyrosine in a dose-timing study in healthy subjects. Clin Ther. 2013 Aug;35(8):1162-1173.e8. doi: 10.1016/j.clinthera.2013.06.011. Epub 2013 Jul 31.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: April 6, 2011
• First Submitted That Met QC Criteria: April 11, 2011
• First Posted (ESTIMATE): April 13, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): May 19, 2011
• Last Update Submitted That Met QC Criteria: May 18, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Pharmacodynamics
• Other Study ID Numbers: LX4211.1-104-NRM; LX4211.104 (OTHER: Lexicon Pharmaceuticals, Inc.)