Study to Evaluate the Effect of Single Doses of LX4211 and Canagliflozin on Intestinal Glucose Absorption in Healthy Adult Subjects

A Phase 1, Single-center, Partially Double-blind, Randomized, Single-dose, 3-Period Crossover Study to Assess the Pharmacodynamic Effects of LX4211 and INVOKANA™ (Canagliflozin) in Healthy Subjects Using Stable Isotope Tracer Methods

The purpose of this study is to assess the effect of LX4211 and the comparator drug canagliflozin on intestinal glucose absorption and metabolism after a single dose in healthy subjects in comparison to placebo.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: LX4211 400 mg; Drug: canagliflozin 300 mg; Drug: LX4211 Placebo

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Lexicon Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult subjects ≥18 to ≤55 years of age
• Vital signs at Screening in the following ranges: systolic blood pressure, 90-140 mmHg; diastolic blood pressure, 50-90 mmHg; heart rate, 45-100 bpm
• Body mass index (BMI) ≥18 and ≤35 kg/sq m
• Willing and able to provide written informed consent

Exclusion Criteria:

• Use of any medication (prescription, over-the-counter, herbal tea, or supplements) within 7 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 LX4211 or canagliflozin
• Daily use of >5 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 bowel resection, any malabsorptive disorder, severe gastroparesis, any GI procedure for the purpose of weight loss which would slow gastric emptying
• History of any major surgery within 6 months prior to Screening
• History of any hypersensitivity to the inactive components of LX4211, inactive components of canagliflozin, acetaminophen oral solution or any inactive component of acetaminophen liquid preparation
• 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 prior to Day -1
• History of alcohol or substance abuse within 2 years prior to Day 1
• History of hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), HIV-1 or HIV-2
• Donation or loss of >500 mL of blood or blood product within 56 days of Day -1
• positive pregnancy test at Screening or Day -1
• Positive urine screen for drugs of abuse at Screening or Day -1
• Positive breath test for alcohol at Screening or Day -1
• Inability or difficulty swallowing whole tablets
• 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: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LX4211; 400 mg of LX4211	Drug: LX4211 400 mg; Drug: canagliflozin 300 mg; Drug: LX4211 Placebo
Active Comparator: Canagliflozin; 300 mg canagliflozin	Drug: LX4211 400 mg; Drug: canagliflozin 300 mg; Drug: LX4211 Placebo
Placebo Comparator: Placebo; LX4211 placebo	Drug: LX4211 400 mg; Drug: canagliflozin 300 mg; Drug: LX4211 Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in rate of glucose appearance after meal (RaO)	Days 1, 8, 15

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of total glucose appearance (RaT)	Days 1, 8, 15
Change from baseline in fasting plasma glucose	Days 1, 8, 15
Change from baseline in postprandial glucose	Days 1, 8, 15
Change from baseline in insulin	Days 1, 8, 15

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Investigators: Study Director: Paul Strumph, M.D., Lexicon Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Powell DR, Zambrowicz B, Morrow L, Beysen C, Hompesch M, Turner S, Hellerstein M, Banks P, Strumph P, Lapuerta P. Sotagliflozin Decreases Postprandial Glucose and Insulin Concentrations by Delaying Intestinal Glucose Absorption. J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1235-49. doi: 10.1210/clinem/dgz258.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: July 29, 2013
• First Submitted That Met QC Criteria: August 2, 2013
• First Posted (Estimate): August 6, 2013

Study Record Updates

• Last Update Posted (Estimate): October 30, 2013
• Last Update Submitted That Met QC Criteria: October 28, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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; Canagliflozin
• Other Study ID Numbers: LX4211.1-111-NRM; LX4211.111 (Other Identifier: Lexicon Pharmaceuticals, Inc.)