Safety, Tolerability, and Efficacy of ISIS-PTP1BRx in Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and efficacy of ISIS-PTP1BRx + oral antidiabetic drug/s (metformin and/or sulfonylurea) versus placebo + oral antidiabetic drug/s.

Official Title
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A Double Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of ISIS 404173 Administered Once Weekly to Obese Patients With Type 2 Diabetes Mellitus Being Treated With Metformin or Metformin Plus Sulfonylurea

Conditions
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Type 2 Diabetes Mellitus, Obese

Intervention / Treatment
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* Drug: ISIS-PTP1BRx
* Drug: Placebo
* Drug: daily OAD (metformin and/or sulfonylurea)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) >/= 27 kg/m2 HbA1c between 7.5% and 10.5% (inclusive) C-Peptide (fasting) greater than or equal to 500 pmol/L On stable dose of metformin alone or in combination with a stable dose of sulfonylurea for >/= 3 months prior to screening, and remain on stable dose throughout the study Agree to conduct home-based (fasted) blood glucose testing as directed Exclusion Criteria: Clinically significant abnormalities in medical history or physical exam Serum creatinine > ULN at Screening Clinical signs or symptoms of liver disease, acute or chronic hepatitis, or ALT or AST > 1.5x ULN at Screening History of renal transplantation or renal dialysis GFR < 60 mL/min at Screening History of diabetic ketoacidosis History of greater than 3 episodes of severe hypoglycemia within 6 months of screening Allergy to sulfur containing drugs Treatment with other drugs or medications not allowed per study specific Disallowed Concomitant Medicines Any other significant illness or condition that may interfere with the patient participating or completing the study Inability or unwillingness to comply with protocol or study procedures

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ISIS-PTP1BRx<br>Weekly Dosing for 26 Weeks | Drug: ISIS-PTP1BRx<br> <br> Drug: daily OAD (metformin and/or sulfonylurea)<br> <br> |
| Placebo Comparator: Placebo<br>Weekly Dosing for 26 Weeks | Drug: Placebo<br> <br> Drug: daily OAD (metformin and/or sulfonylurea)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, severity, dose-relationship of adverse effects, and changes in laboratory evaluations as a measure of safety |  | 38 weeks | 
| Change in plasma HbA1c levels at Week 27 compared to Baseline as a measure of efficacy |  | 27 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FPG, weekly average SMPG, seven-point glucose profile, lipid profile, body weight, & BMI at Week 27 compared to Baseline as a measure of efficacy |  | 27 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes Mellitus, T2DM