Safety, Tolerability, and Activity of ISIS 113715 in People With Type 2 Diabetes Mellitus Being Treated With Sulfonylurea

Study Overview
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Brief Summary
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The aim of this study is to evaluate the safety, tolerability, and pharmacokinetics of two ISIS 113715 subcutaneous doses (15 mg and 30 mg/day) in combination with oral antidiabetic agents (OAD) versus OAD + placebo in patients with inadequately controlled type 2 diabetes, despite ongoing maximal treatment with OAD.

Official Title
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A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of ISIS 113715 Administered Daily in Patients With Type 2 Diabetes Mellitus Being Treated With Sulfonylurea

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: ISIS 113715


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female (post-menopausal and/or surgically sterile) Aged 18 to 70 years Diagnosed with type 2 diabetes mellitus of eight years or less in duration Being treated with OAD at stable maximum doses [defined as at least 10 mg/day glibenclamide (preferred), or 20 mg/day glipizide, with or without at least 1,500 mg/day metformin] for at least three months prior to screening Having fasting plasma glucose levels of 150-270 mg/dL and HbA1c levels of 7.5-11.0% Exclusion Criteria: Greater than 3 severe hypoglycemic episodes within six months of screen Pregnant, breastfeeding, or intends to become pregnant Clinical signs or symptoms of liver disease, acute, or chronic hepatitis, or ALT greater than the upper limit of normal Positive hepatitis B surface antigen, hepatitis C antibody, or HIV test Patients with history of renal transplantation or renal dialysis or microalbuminuria defined as urine albumin > 200 mg/day History of insulin use within three months of screen History of diabetic ketoacidosis Treatment with any thiazolidinedione (e.g., rosiglitazone) within three months of screen History of lactic acidosis while on metformin therapy Complications of diabetes (e.g., neuropathy, nephropathy, and retinopathy) Clinically significant and currently active diseases Clinical significant abnormalities in medical history, physical examination, or laboratory examination

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ISIS 113715|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the safety, tolerability, and pharmacokinetics of two ISIS 113715 subcutaneous dosages in combination with OAD versus OAD + placebo. |  |  | 
| Examine the effect of treatment with 15 and 30 mg/day ISIS 113715 on fasting plasma glucose and HbA1c. |  |  | 
| Evaluate the effects of ISIS 113715 on insulin sensitivity, B-cell function, proinsulin/insulin ratio, fasting insulin, C-peptide and proinsulin. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fasting plasma glucose, HbA1c, Oral antidiabetic agent(s)