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
Overview
- Phase
- Phase 2
- Intervention
- MBX-2044
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- CymaBay Therapeutics, Inc.
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Determine the maximum tolerated dose (MTD) of MBX-2044, after 14 days administration
- Status
- Completed
- Last Updated
- 11 years ago
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.
Investigators
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/m
- •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.
Arms & Interventions
MBX-2044 1.5 mg
Intervention: MBX-2044
MBX-2044 4.5 mg
Intervention: MBX-2044
MBX-2044 15 mg
Intervention: MBX-2044
MBX-2044 30 mg
Intervention: MBX-2044
MBX-2044 60 mg
Intervention: MBX-2044
MBX-2044 90 mg
Intervention: MBX-2044
Placebo
Intervention: Placebo for MBX-2044
Outcomes
Primary Outcomes
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
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