DDI Study With Multiple-dose LX4211 and Single Dose Digoxin

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Treatment A digoxin
* Drug: Treatment B LX4211
* Drug: Treatment C Digoxin + 400 mg LX4211 administered concomitantly


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events |  | Day 1-Day 26 |