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

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

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Schedule A
* Drug: Schedule B
* Drug: Schedule C
* Drug: Schedule D
* Drug: Schedule E


Participation Criteria
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Eligibility Criteria
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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.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LX4211<br>400 mg of LX4211 administered orally | Drug: Schedule A<br>* Dosing 1 hour before breakfast<br>Drug: Schedule B<br>* Dosing 0.5 hour before breakfast<br>Drug: Schedule C<br>* Dosing immediately before breakfast<br>Drug: Schedule D<br>* Dosing immediately before lunch<br>Drug: Schedule E<br>* Split dose, dosing 1 hour before breakfast and dinner<br>|
| Placebo Comparator: Placebo<br>Nonidentical placebo administered orally | Drug: Schedule A<br>* Dosing 1 hour before breakfast<br>Drug: Schedule B<br>* Dosing 0.5 hour before breakfast<br>Drug: Schedule C<br>* Dosing immediately before breakfast<br>Drug: Schedule D<br>* Dosing immediately before lunch<br>Drug: Schedule E<br>* Split dose, dosing 1 hour before breakfast and dinner<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacodynamics