Study to Evaluate the Pharmacodynamic and Pharmacokinetic Effects of LX4211 in Subjects With Type 2 Diabetes and Renal Impairment

Study Overview
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Brief Summary
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This Phase 1 study is intended to assess the pharmacodynamics (PD), pharmacokinetics (PK), safety and tolerability of LX4211 following once daily oral administration in subjects with type 2 diabetes mellitus (T2DM) and moderate to severe renal impairment.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled Parallel Group Study to Evaluate the Pharmacodynamic and Pharmacokinetic Effects of LX4211 in Subjects With Type 2 Diabetes Mellitus and Moderate to Severe Renal Impairment

Conditions
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Type 2 Diabetes Mellitus, Renal Impairment

Intervention / Treatment
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* Drug: LX4211
* Drug: LX4211 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥18 to ≤80 years of age History of T2DM for at least 6 months prior to screening Moderate to severe renal impairment and not actively on dialysis Willing and able to perform self-monitoring of blood glucose Willing and able to provide written informed consent Exclusion Criteria: History of type 1 diabetes mellitus, diabetic ketoacidosis (within the previous 6 months), or diabetes resulting from pancreatic disorder or secondary diabetes (from acromegaly and/or Cushing's disease) Subjects who have received a renal allograft Subjects expecting to require dialysis or to undergo kidney transplantation within 3 months of study dosing Presence of active hepatic disease or clinically significant abnormal liver function tests at Screening or planned study Day -1 Subjects with a history of heart attack, severe/unstable angina, or coronary revascularization procedure within 6 months prior to study Day -2 History of clinically significant cardiac arrhythmias within 1 year prior to study Day -2 Subjects with congestive heart failure Subjects with uncontrolled Stage III hypertension History of 2 or more emergency room visits, doctors' visits, or hospitalizations due to hypoglycemia within the 6 months prior to planned study Day -2 History of alcohol or illicit drug abuse within 1 year prior to Screening History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C Major surgery within 6 months prior to planned study Day -2 History of any malignancy within the last 5 years Triglycerides >1000 mg/dL at Screening or planned study Day -1 History of any serious adverse reaction or hypersensitivity to an SGLT inhibitor Use of corticosteroids within 2 weeks prior to study Day 1 Use of any investigational drug within 30 days prior to study Day 1, or investigational protein or antibodies within 60 days of Day 1 Positive urine pregnancy test at Screening Positive urine screen for illicit drug abuse at Screening Prior exposure to LX4211

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Treatment A<br> | Drug: LX4211<br>* Subjects will receive LX4211 once daily for 7 days<br>|
| Placebo Comparator: LX4211 Placebo<br> | Drug: LX4211 Placebo<br>* Subjects will receive LX4211 placebo once daily for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in postprandial glucose |  | baseline to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects experiencing an adverse event |  | 7 days | 
| Change from baseline in fasting plasma glucose |  | baseline to 7 days | 
| Change from baseline in glucagon-like peptide 1 (Glp-1) |  | baseline to 7 days | 
| Area Under Curve (AUC) |  | Days 1 and 7; predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose |