Study to Evaluate the Effect of ISIS GCGRRx on Hepatic Lipid and Glycogen Content 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 effect of ISIS 449884 (ISIS-GCGRRX) on Hepatic Lipid and Glycogen Content in patients with Type 2 Diabetes being treated with Metformin.

Official Title
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Double Blind, Randomized, Placebo-Controlled, Phase 2A Mechanistic Study to Evaluate the Effect of ISIS 449884 (ISIS-GCGRRx) on Hepatic Lipid and Glycogen Content in Patients With Type 2 Diabetes Being Treated With Metformin

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: ISIS-GCGRRx
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age 18 to 75 BMI ≥ 25.0 kg/m2 < 36.0 kg/m2 HbA1c ≥ 7.5% and ≤ 10.5% Type 2 Diabetes Mellitus and on stable dose of Metformin. Patients must have been on a stable dose of oral metformin (at least 1000 mg/day) for a minimum of 3 months prior to screening evaluation and will be required to continue their stable dose of metformin throughout the study. Patients on a stable dose of metformin plus a sulfonylurea (SU) or metformin plus a dipeptidyl peptidase-IV (DPPIV) inhibitor for a minimum of 3 months prior to Screening evaluation may be allowed Agree to conduct home-based (fasted) blood glucose testing as directed Exclusion Criteria: Clinically significant abnormalities in medical history or physical exam Show evidence of uncorrected hypothyroidism or hyperthyroidism History of liver transplantation or renal dialysis History of liver disease History of greater than 3 episodes of severe hypoglycemia within 6 months of screening Treatment with any other antidiabetic drug(s) other than metformin, SU or DPPIV within 3 months of screening History of diabetic ketoacidosis 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: 75 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ISIS-GCGRRx<br>ISIS-GCGRRx once weekly dosing for 13 weeks | Drug: ISIS-GCGRRx<br>* once weekly dosing for 13 weeks<br>* Other names: ISIS 449884;|
| Placebo Comparator: Placebo<br>once weekly dosing for 13 weeks | Drug: Placebo<br>* once weekly dosing for 13 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fasting hepatic glycogen content | Change from Baseline | Week 14 | 
| Change in fasting hepatic lipid content | Change from Baseline | Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability will be assessed by determining the incidence, severity, dose relationship of adverse effects, and changes in laboratory evaluations | Safety results in patients dosed with ISIS 449884 will be compared with those from patients dosed with placebo | 38 weeks |