Safety and Tolerability Study of MBX-2044 in Patients With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to collect important information regarding the glucose-lowering efficacy of MBX-2044 and the safety of MBX-2044 (especially weight gain and edema) in diabetics. It will also provide important information about the appropriate doses to be used in subsequent longer-term studies to evaluate the safety and efficacy of MBX-2044 alone and in combination with other anti-diabetic agents.

Detailed Description
-----------------
The current study is designed to test the short-term effectiveness and tolerability of MBX-2044 in patients with type 2 diabetes who are currently being controlled with up to one or two non-TZD hypoglycemic agent(s) including sulfonylureas, meglitinides, metformin, α-glucosidase inhibitors or Byetta®. Eligible patients will be enrolled into one of the following treatment cohorts receiving either placebo or MBX-2044 at 1.5, 4.5, 15, 30, or 60 mg/day in a double-blinded study for a 14-day treatment period. Patients will be evaluated for adverse events and vital signs daily. All efficacy and laboratory safety measures will be assessed after 2 weeks. This study will provide important information regarding the glucose-lowering efficacy of MBX-2044 and the safety of MBX-2044 (especially weight gain and edema) in diabetics. It will also provide important information about the appropriate doses to be used in subsequent longer-term studies to evaluate the safety and efficacy of MBX-2044 alone and in combination with other anti-diabetic agents.

Official Title
-----------------
Phase 2a, Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study of MBX-2044 to Evaluate the Multiple-dose Pharmacokinetics, Safety and Tolerability When Administered Orally in Patients With Type 2 Diabetes

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

Intervention / Treatment
-----------------
* Drug: MBX-2044
* Drug: MBX-2044
* Drug: MBX-2044
* Drug: MBX-2044
* Drug: MBX-2044
* Drug: MBX-2044
* Drug: Placebo for MBX-2044


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 2 diabetes previously controlled with up to one or two non-TZD hypoglycemic agents including sulfonylureas (e.g., glyburide, glipizide, glimeprimide), meglitinides (e.g., Prandin®, Starlix®), metformin (e.g., Glucophage®), α-glucosidase inhibitors (e.g.,acarbose, miglitol) or Byetta® All female patients must be either surgically sterile or post-menopausal. Male patients with female partners of childbearing potential must agree to use condoms, or their partner must use a medically acceptable form of contraception. BMI 24-44 kg/m2. Patients must have a FPG ≤ 200 mg/dL at screening. Patients must have Hemoglobin A1c ≥ 6.5%, ≤ 10.0% at screening. Electrocardiogram (ECG) and chest x-ray must be normal, or considered not clinically significant, for participation in this study. Patients must have a blood pressure ≤ 160/90 mm/hg including hypertensive patients controlled with medication. Exclusion Criteria: History of Type 1 diabetes or diabetes secondary to pancreatitis or pancreatectomy. History of TZD use (Actos or Avandia) within 6 months of Screening Visit. History of TZD discontinuation due to lack of efficacy. History of congestive heart failure within last 5 years. History of significant pulmonary disease, myocardial infarction, cerebrovascular accident, or nephrotic syndrome within last 1 year. Malignancy within the last 5 years (except resected basal cell carcinoma). Ongoing active infection. Change in treatment with lipid-lowering agent within 7 days of screening visit. Current or expected requirement for anticoagulant therapy [except for low-dose aspirin ≤ 325 mg/d or Plavix® ≤ 75 mg/d]. Current or expected treatment with phenytoin for the duration of the study. Known hypersensitivity to NSAIDs.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MBX-2044 1.5 mg<br> | Drug: MBX-2044<br>* MBX-2044 1.5 mg one capsule daily for 14 days<br>|
| Experimental: MBX-2044 4.5 mg<br> | Drug: MBX-2044<br>* MBX-2044 4.5 mg three 1.5 mg capsules daily for 14 days<br>|
| Experimental: MBX-2044 15 mg<br> | Drug: MBX-2044<br>* MBX-2044 15 mg one capsule daily for 14 days<br>|
| Experimental: MBX-2044 30 mg<br> | Drug: MBX-2044<br>* MBX-2044 30 mg two 15 mg capsules daily for 14 days<br>|
| Experimental: MBX-2044 60 mg<br> | Drug: MBX-2044<br>* MBX-2044 60 mg one capsule daily for 14 days<br>|
| Experimental: MBX-2044 90 mg<br> | Drug: MBX-2044<br>* MBX-2044 90 mg one 60 mg capsule and two 15 mg capsules daily for 14 days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo for MBX-2044<br>* Placebo Intervention<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the multiple-dose pharmacokinetics of MBX-2044 administered as monotherapy at the protocol-specified daily dose orally for 14 days |  |  | 
| Evaluate the clinical safety and tolerability of MBX-2044 after 14 days administration, including the parameters of weight gain and edema |  |  | 
| Determine the maximum tolerated dose (MTD) of MBX-2044, after 14 days administration |  |  | 
| Determine the effect of MBX-2044 after 14 days administration, on efficacy parameters |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type 2 Diabetes Mellitus