A Study to Evaluate the Pharmacodynamic Effects of Single-Dose Co-Administration of LX4211 With Januvia® in Type 2 Diabetics

Study Overview
=================
Brief Summary
-----------------
This study is intended to evaluate the pharmacodynamics, safety, and tolerability of LX4211 when administered concurrently with sitagliptin (Januvia®) in patients with Type 2 Diabetes Mellitus.

Official Title
-----------------
A Phase 1, Open-label, 3-period, 3-treatment, Single Dose Crossover Study to Evaluate the Pharmacodynamic Effects of LX4211 When Administered Concurrently With JANUVIA® (Sitagliptin) in Subjects With Type 2 Diabetes Mellitus

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: LX4211
* Drug: Januvia®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults aged 18 to 65 years of age History of Type 2 Diabetes Mellitus for at least 3 months prior to Screening, with HgbA1c values of 6.5 to 10.5% and C-peptide ≥1.0 ng/mL Body mass index (BMI) ≤45 kg/sq m Willing and able to self-monitor blood glucose Able to provide written informed consent Exclusion Criteria: History of Type 1 diabetes mellitus, diabetic ketoacidosis, hyperosmolar nonketotic syndrome, or diabetes resulting from pancreatic disorder or secondary diabetes Current use of any blood glucose lowering agent other than metformin History of renal disease or clinically significant abnormal kidney function tests at Screening or Day -2 Presence of active hepatic disease or clinically significant abnormal liver function tests at Screening or Day -2 History of myocardial infarction, severe/unstable angina, or coronary revascularization procedure within 6 months of Day -2 History of clinically significant cardiac arrhythmias within 1 year of Day -2 Congestive heart failure and/or New York Heart Association (NYHA) class III or IV symptoms of heart failure Subjects with uncontrolled Stage 3 hypertension History of 2 or more emergency room visits, doctor's visits, or hospitalizations due to hypoglycemia within 6 months of Day -2 History of alcohol or drug abuse within 12 months of Screening History of bowel resection > 20 cm, any malabsorptive disorder, severe gastroparesis, and GI procedure for the purpose of weight loss that would slow gastric emptying History of HIV or hepatitis C Major surgery within 3 months of Day -2 or any planned surgery during the study History of any active infection within 2 weeks of Day -2 History of pancreatitis History of any malignancy within the last 5 years which would affect the diagnosis or assessment of LX4211 or sitagliptin History of any serious adverse reaction or hypersensitivity to LX4211 or sitagliptin Presence of any clinically significant physical, laboratory, or ECG findings or any concurrent condition at Screening that may interfere with the study in the opinion of the investigator Triglycerides > 1000 mg/dL at Screening or Day -2 Donation or loss of >400 mL of blood or blood product within 8 weeks prior to Day -2 Use of any tobacco product for the duration of study participation Use of corticosteroids within 2 weeks of Day 1 Use of digoxin or warfarin within 2 weeks prior to Screening

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br> | Drug: LX4211<br>* 400 mg of LX4211 administered as two 200 mg tablets<br>|
| Experimental: Treatment C<br> | Drug: LX4211<br>* 400 mg of LX4211 administered as two 200 mg tablets<br>Drug: Januvia®<br>* 100 mg Januvia® (sitagliptin) administered as one 100 mg sitagliptin tablet<br>|
| Active Comparator: Treatment B<br> | Drug: Januvia®<br>* 100 mg Januvia® (sitagliptin) administered as one 100 mg sitagliptin tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in gut hormones |  | Days 1, 8, and 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in fasting plasma glucose |  | Days 1, 8, and 15 | 
| Change from baseline in postprandial glucose |  | Days 1, 8, and 15 | 
| Change from baseline in insulin |  | Days 1, 8, and 15 | 
| Change from baseline in peptide YY |  | Days 1, 8, and 15 | 
| Change from baseline in urinary glucose excretion |  | Days 1, 8, and 15 |