Study of Two Oral Formulations of LX4211 in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This protocol is intended to compare the effects of both a solid (tablet) and liquid oral dosage form of LX4211 in subjects with type 2 diabetes mellitus.

Official Title
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A Phase 1, Randomized, Open-Label, Three-Way Crossover Study of Two Oral Formulations of LX4211 in Subjects With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: 300 mg LX4211 (150 mg tablets)
* Drug: 300 mg LX4211 (50 mg tablets)
* Drug: 300 mg LX4211 (liquid)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18 to 65 years of age Males and females of non-childbearing potential Diagnosis of type 2 diabetes mellitus for at least 6 months prior to screening Fasting plasma glucose ≤240 mg/dL Body mass index <42 kg/sq m HbA1c of 7-11% C-peptide of ≥1.0 ng/mL Ability to provide written informed consent Exclusion Criteria: History of type 1 diabetes mellitus, diabetic ketoacidosis, hyperosmolar nonketonic syndrome, incontinence, or nocturia Current use of any blood glucose-lowering agent other than metformin Exposure to insulin, thiazide, or loop diuretics within 4 weeks prior to screening History of HIV, Hepatitis B, or Hepatitis C Surgery within 6 months of screening Donation or loss of >400 mL of blood or blood product within 8 weeks prior to start of study Use of proteins or antibodies within 12 weeks prior to screening. (Flu shots are allowed.) Exposure to any investigational agent or participation in an investigational trial within 30 days of the start of the study History of drug or alcohol abuse within 12 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Solid Oral Dose - 150 mg tablets<br> | Drug: 300 mg LX4211 (150 mg tablets)<br>* Single oral dose of two 150 mg tablets LX4211<br>|
| Experimental: Solid Oral Dose - 50 mg tablets<br> | Drug: 300 mg LX4211 (50 mg tablets)<br>* Single oral dose of six 50 mg tablets LX4211<br>|
| Experimental: Liquid Oral Dose<br> | Drug: 300 mg LX4211 (liquid)<br>* Single 30 mL dose of liquid oral solution LX4211 (10 mg/mL)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration |  | Pharmacokinetics samples collected on day of dosing and 24 and 48 hours post-dose (Follow-up). | 
| Time at which maximum observed plasma concentration occurs |  | Pharmacokinetics samples collected on day of dosing and 24 and 48 hours post-dose (Follow-up). | 
| Half-life of the drug in plasma |  | Pharmacokinetics samples collected on day of dosing and 24 and 48 hours post-dose (Follow-up). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma glucose |  | Samples collected on initial visit; Day -15 and Day -5 (Washout); numerous timepoints on Day -1 (Washout) and day of dosing; 24 hours post-dose (Follow-up); and upon discharge. | 
| Urinary glucose excretion |  | Samples collected on Day -1 (Washout), day of dosing, and 24 and 48 hours post-dose (Follow-up). | 
| Insulin |  | Samples collected on initial visit; Day -15 and Day -5 (Washout); numerous timepoints on Day -1 (Washout) and day of dosing; 24 hours post-dose (Follow-up); and upon discharge. | 
| Peptide YY |  | Samples collected on initial visit; Day -15 and Day -5 (Washout); numerous timepoints on Day -1 (Washout) and day of dosing; 24 hours post-dose (Follow-up); and upon discharge. | 
| Glucagon-like Peptide 1 |  | Samples collected on initial visit; Day -15 and Day -5 (Washout); numerous timepoints on Day -1 (Washout) and day of dosing; 24 hours post-dose (Follow-up); and upon discharge. |