A Study to Characterize Regimens of Basal Insulin Intensified With Either Symlin® or Rapid Acting Insulin in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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This will be a randomized, open label, parallel group, multicenter study. There will be two phases in the study. Phase 1 (Baseline to Week 24) will compare the efficacy and safety of regimens of basal insulin intensified with either Symlin or rapid acting insulin in patients with type 2 diabetes who have either been on a prior regimen of insulin for less than 6 months and were taking less than 50 U total of insulin per day OR are candidates for the initiation of insulin therapy. The purpose of Phase 2 (Week 24 to Week 36) is to explore further intensification of diabetes regimens in patients failing to achieve HbA1c <=6.5% at Week 24.

Official Title
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A Phase 4, Randomized, Open Label, Parallel Group, Multicenter Study to Characterize Regimens of Basal Insulin Intensified With Either Symlin® or Rapid Acting Insulin in Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: pramlintide acetate (Symlin)
* Drug: rapid acting insulin (Humalog® [insulin lispro], Novolog® [insulin aspart], or Apidra® [insulin glulisine])
* Drug: basal insulin (Lantus® [insulin glargine], or Levemir® [insulin detemir])


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a clinical diagnosis of type 2 diabetes mellitus Has an HbA1c >7.0% and ≤10.0% Has a BMI of ≥25 kg/m^2 and ≤50 kg/m^2 Has been on a regimen of insulin for less than 6 months and is taking less than 50 U total of insulin per day, OR has not been on a pre existing insulin regimen and is a candidate for the initiation of basal insulin therapy Exclusion Criteria: Has experienced recurrent severe hypoglycemia requiring assistance during the past 6 months Requires the use of drugs that stimulate gastrointestinal motility Has been previously treated with Symlin (or has participated in a Symlin clinical study) Is currently being treated with any of the following medications: *Over-the-counter antiobesity agents (including, but not limited to, herbal supplements) or prescription antiobesity agents (including orlistat [Xenical®] and sibutramine [Meridia®]); *Oral, intravenous, or intramuscular systemic steroids by oral or potent inhaled or intrapulmonary steroids that are known to have a high rate of systemic absorption; *Drugs that directly affect gastrointestinal motility, including but not limited to: dopamine antagonists (e.g., metoclopramide [Reglan®]), opiates or anticholinergics; and chronic (more than 10 days within a 6-month period) macrolide antibiotics such as erythromycin and newer derivatives; *Investigational medications Has a history or presence of any of the following: *Eating disorders (including anorexia and/or bulimia); *Bariatric surgery (gastric bypass, gastric banding, or gastroplasty) Is currently enrolled in a weight-loss program or plans to enroll in a weight-loss program before termination of the study Has donated blood within 30 days of study start or plans to donate blood during the duration of the study

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br> | Drug: pramlintide acetate (Symlin)<br>* subcutaneous injection (60 mcg or 120 mcg), immediately prior to major meals<br>* Other names: Symlin;Drug: basal insulin (Lantus® [insulin glargine], or Levemir® [insulin detemir])<br>* subcutaneous injection, dosing based on titration guidelines<br>|
| Active Comparator: Group B<br> | Drug: rapid acting insulin (Humalog® [insulin lispro], Novolog® [insulin aspart], or Apidra® [insulin glulisine])<br>* subcutaneous injection, dosing based on titration guidelines<br>Drug: basal insulin (Lantus® [insulin glargine], or Levemir® [insulin detemir])<br>* subcutaneous injection, dosing based on titration guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Patients Achieving HbA1c <=7% at Week 24 With no Gain in Body Weight From Baseline and no Incidence of Severe Hypoglycemia | A severe hypoglycemia is defined as an event during which the patient required the assistance of another individual (including aid in ingestion of oral carbohydrate); and/or required the administration of glucagon injection, intravenous glucose, or other medical intervention. | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving HbA1c <=7% at Week 24 | This is a component of the primary endpoint | 24 Weeks | 
| Percentage of Patients With no Weight Gain at Week 24 | This is a component of the primary endpoint | 24 Weeks | 
| Percentage of Patients With a Severe Hypoglycemia Adverse Event | This is a component of the primary endpoint. | 24 Weeks | 
| Change in HbA1c From Baseline at Week 24 | Baseline values are presented in the Baseline Characteristics section | From Baseline to Week 24 | 
| Change in Body Weight From Baseline at Week 24 | Baseline values are presented in the Baseline Characteristics section | From Baseline to Week 24 | 
| Change in Waist Circumference From Baseline at Week 24 | Baseline values are presented in the Baseline Characteristics section | From Baseline to Week 24 | 
| Change in Fasting Plasma Glucose From Baseline at Week 24 | Baseline values are presented in the Baseline Characteristics section | From Baseline to Week 24 | 
| Fasting Serum Lipids Change From Baseline to Week 24 |  | Baseline, week 24 | 
| Phase 2: Change in HbA1c at Week 36 | Two changes are calculated, the first by subtracting Week 36 value from the Phase 1 Baseline value (total change over 36 weeks), the second by subtracting the Week 36 value from the Phase 2 Baseline value (change from week 24 to week 36 only). | Phase 1 Baseline, Phase 2 Baseline at Week 24, Week 36 | 
| Phase 2: Change in Body Weight at Week 36 | Two changes are calculated, the first by subtracting Week 36 value from the Phase 1 Baseline value (total change over 36 weeks), the second by subtracting the Week 36 value from the Phase 2 Baseline value (change from week 24 to week 36 only). | Phase 1 Baseline, Phase 2 Baseline at Week 24, Week 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Symlin, Amylin, insulin, Humalog, Novolog, Apidra