DDI Study With Multiple-dose LX4211 and Single Dose Digoxin

A Phase 1, Single-center, Open-label, Two-period, Single-sequence, Drug-drug Interaction Study to Evaluate the Effects of Multiple-dose LX4211 on the Pharmacokinetics of Single-dose Digoxin (Lanoxin®), a Sensitive P-glycoprotein (P-gp) Substrate, in Healthy Male and Female Subjects

This study will be conducted as a single-center, open-label, 2-period, single-sequence, drug-drug interaction study to assess the effects of multiple dose LX4211 (400 mg administered as 2 × 200-mg tablets qd × 12 days) on the PK of single-dose digoxin (2 × 0.25-mg tablets) in healthy male and female subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Treatment A digoxin; Drug: Treatment B LX4211; Drug: Treatment C Digoxin + 400 mg LX4211 administered concomitantly

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • 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 ≤32 kg/sq m
• Willing and able to provide written informed consent

Exclusion Criteria:

• Presence of clinically significant physical, laboratory, or ECG findings that, in the opinion of the Investigator and/or Sponsor, may interfere with any aspect of study conduct or interpretation of results
• History of clinically significant arrhythmias
• History of cardiac arrhythmias or palpitations associated with presyncope, syncope, or a family history of sudden cardiac death
• Use of any medications or supplements/supratherapeutic doses of vitamins within 14 days prior to the first dose administration and throughout the duration of the study
• Receipt of any investigational agent or study drug within 30 days prior to Screening
• Receipt of any protein- or antibody-based therapeutic agents within 3 months prior to Screening
• Prior exposure to LX4211
• Use of tobacco, smoking cessation products, or products containing nicotine within 3 months prior to Screening and for the duration of the study
• History of any serious adverse reaction or hypersensitivity to any inactive component of LX4211 or digoxin
• Existence of any surgical or medical condition that might interfere with the absorption, distribution, metabolism, or excretion of LX4211 or digoxin
• History of any major surgery within 6 months or anticipated surgery prior to Day 1
• History of any clinically significant hypoglycemia or hyperglycemia
• History of renal disease, or significantly abnormal kidney function test at Screening
• History of hepatic disease, or significantly abnormal liver function tests at Screening
• History of any clinically relevant psychiatric, renal, hepatic, pancreatic, endocrine, cardiovascular, neurological, hematological, or GI abnormality
• History of any active infection within 14 days prior to Day 1
• History of alcohol or substance abuse within 2 years prior to Screening
• Positive hepatitis panel
• Donation or loss of >500 mL of blood or blood product within 3 months prior to Screening
• Women who are breastfeeding or are planning to become pregnant during the study, or women who have a positive serum pregnancy test
• Positive urine glucose at Screening
• Positive urine screen for drugs of abuse and cotinine at Screening, Day -1, or Day 13
• Inability or difficulty swallowing whole tablets
• Unable or unwilling to cooperate with the Investigator for any reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment B; 400 mg oral LX4211 qd administration	Drug: Treatment B LX4211; 400 mg LX4211 administered daily on Day 14 through Day 25
Experimental: Treatment A; 0.5 mg single-dose oral digoxin administration	Drug: Treatment A digoxin; 0.5 mg digoxin administered on Day 1 and Day 20
Experimental: Treatment C; 0.5 mg single-dose oral digoxin administration + 400 mg oral LX4211 qd administration	Drug: Treatment C Digoxin + 400 mg LX4211 administered concomitantly; 0.5 mg Digoxin + 400 mg LX4211 administered concomitantly on Day 20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC	Day 1-Day 7, Day 20-26

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse Events	Day 1-Day 26

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: November 20, 2014
• First Submitted That Met QC Criteria: November 24, 2014
• First Posted (Estimate): November 25, 2014

Study Record Updates

• Last Update Posted (Estimate): July 9, 2015
• Last Update Submitted That Met QC Criteria: July 8, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Sodium-Glucose Transporter 2 Inhibitors; Digoxin; (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: LX4211.1-114-NRM; LX4211.114 (Other Identifier: Lexicon Pharmaceuticals, Inc.)