Study to Define the Electrocardiogram Effects of a Single Dose of LX4211 in Healthy Subjects

Randomized, Double-blind, Placebo-controlled, Positive-controlled, 4-period, 4-way Crossover Study to Define the Electrocardiogram Effects of a Single Dose of LX4211 800 mg and 2000 mg Compared With Placebo and Open-label Moxifloxacin in Healthy Subjects: A Thorough QT Study

This Phase 1 study is to investigate the effects of higher doses of LX4211 (800 mg and 2000 mg) do not differ from placebo in the mean change in QTcI from Baseline in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: LX4211 Placebo; Drug: LX4211 800 mg; Drug: LX4211 2000 mg; Drug: moxifloxacin 400 mg

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • 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:

• 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
• Able and willing to provide written informed consent
• Nonsmoker and has not used any tobacco products for at least 3 months prior to Screening
• Willing to adhere to the prohibitions and restrictions specified in this protocol
• Able to tolerate prolonged periods of quiet, motionless, supervised rest

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 prior to Screening
• Use of any protein or antibody-based therapeutic agents within 3 months prior to Screening
• Prior exposure to LX4211
• Daily use of cigarettes or any tobacco products within 3 months prior to Screening and while participating in the study
• History of any major surgery within 6 months prior to Screening
• History of any serious adverse reaction or hypersensitivity to any inactive component of LX4211
• History of renal disease or significantly abnormal kidney function tests
• History of hepatic disease or significantly abnormal liver function tests
• Women who are breastfeeding or are planning to become pregnant during the study
• History of any active infection within 14 days prior to Screening
• History of alcohol or substance abuse within 2 years prior to Screening
• History of hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), HIV-1 or HIV-2
• Presence of clinically significant physical, laboratory, or ECG findings (eg, QTcF >450 msec for females and QTcF >430 msec for males) at Screening
• >30 premature ventricular beats per hour on the telemetry ECG monitoring at Day -2 of Period 1
• History of additional risk factors for the presence of a family history of Short QT Syndrome, Long QT Syndrome, sudden unexplained death at a young age (<=40 years), drowning or sudden infant death syndrome in a first degree relative (ie, biological parent, sibling, or child)
• Any skin condition likely to interfere with ECG electrode placement or adhesion
• Any skin condition likely to interfere with ECG electrode placement or adhesion
• Donation or loss of >400 mL of blood or blood product within 3 months prior to Screening
• Positive urine glucose during Screening
• Positive pregnancy test during Screening
• Positive urine screen for drugs of abuse during Screening
• Positive urine test for alcohol during Screening
• Inability or difficulty swallowing whole tablets or capsules
• Unable or unwilling to communicate or cooperate with the Investigator for any reason

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; LX4211 800 mg	Drug: LX4211 Placebo; Drug: LX4211 800 mg; Drug: LX4211 2000 mg; Drug: moxifloxacin 400 mg
Experimental: Treatment B; LX4211 2000 mg	Drug: LX4211 Placebo; Drug: LX4211 800 mg; Drug: LX4211 2000 mg; Drug: moxifloxacin 400 mg
Active Comparator: Treatment C; moxifloxacin 400 mg	Drug: LX4211 Placebo; Drug: LX4211 800 mg; Drug: LX4211 2000 mg; Drug: moxifloxacin 400 mg
Placebo Comparator: Treatment D; Placebo	Drug: LX4211 Placebo; Drug: LX4211 800 mg; Drug: LX4211 2000 mg; Drug: moxifloxacin 400 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in QTc intervals	Day -1, Day 1 of each period (2, 3, 4)

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects experiencing an adverse event	up to 87 days
Plasma concentrations of LX4211	Day 1 of each Period: predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60 hours after dosing time on Day 1 hours

Collaborators and Investigators

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

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: July 29, 2013
• First Submitted That Met QC Criteria: July 29, 2013
• First Posted (Estimate): July 31, 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; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Sodium-Glucose Transporter 2 Inhibitors; Moxifloxacin; (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: LX4211.1-109-NRM; LX4211.109 (Other Identifier: Lexicon Pharmaceuticals, Inc.)