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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: pramlintide acetate (Symlin); Drug: basal insulin (Lantus® [insulin glargine], or Levemir® [insulin detemir]); Drug: rapid acting insulin (Humalog® [insulin lispro], Novolog® [insulin aspart], or Apidra® [insulin glulisine])

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Northport, Alabama, United States
      • Research Site
  • Arizona
    • Phoenix, Arizona, United States
      • Research Site
  • California
    • Loma Linda, California, United States
      • Research Site
  • Colorado
    • Aurora, Colorado, United States
      • Research Site
  • Florida
    • Hollywood, Florida, United States
      • Research Site
    • Maitland, Florida, United States
      • Research Site
    • Miami, Florida, United States
      • Research Site
    • North Miami Beach, Florida, United States
      • Research Site
    • Plantation, Florida, United States
      • Research Site
  • Georgia
    • Roswell, Georgia, United States
      • Research Site
  • Illinois
    • Peoria, Illinois, United States
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States
      • Research Site
  • Kansas
    • Wichita, Kansas, United States
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States
      • Research Site
  • Michigan
    • Detroit, Michigan, United States
      • Research Site
    • Grand Rapids, Michigan, United States
      • Research Site
  • Mississippi
    • Jackson, Mississippi, United States
      • Research Site
  • Missouri
    • St. Louis, Missouri, United States
      • Research Site
  • Montana
    • Butte, Montana, United States
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States
      • Research Site
  • New Jersey
    • Hamilton, New Jersey, United States
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States
      • Research Site
  • New York
    • Albany, New York, United States
      • Research Site
    • Staten Island, New York, United States
      • Research Site
  • Ohio
    • Mentor, Ohio, United States
      • Research Site
  • Oregon
    • Portland, Oregon, United States
      • Research Site
  • Pennsylvania
    • Bridgeville, Pennsylvania, United States
      • Research Site
    • Philadelphia, Pennsylvania, United States
      • Research Site
  • South Carolina
    • Aiken, South Carolina, United States
      • Research Site
  • Tennessee
    • Bartlett, Tennessee, United States
      • Research Site
    • Nashville, Tennessee, United States
      • Research Site
  • Texas
    • Austin, Texas, United States
      • Research Site
    • Dallas, Texas, United States
      • Research Site
  • Washington
    • Olympia, Washington, United States
      • Research Site
    • Spokane, Washington, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoglycemia Adverse Events	MILD: patient reported symptoms consistent with hypoglycemia that may or may not have been documented by glucose monitoring at the time of symptoms. Symptoms did not greatly interrupt or interfere with the patients daily activities. Symptoms dissipated spontaneously or upon eating. MODERATE: Patient reported symptoms consistent with hypoglycemia that may or may not have been documented by glucose monitoring at the time of symptoms. Symptoms interrupted or interfered with the patients daily activities and required immediate self treatment (e.g. carbohydrate ingestion). SEVERE: 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.	36 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Peyrot M, Rubin RR, Polonsky WH, Best JH. Patient reported outcomes in adults with type 2 diabetes on basal insulin randomized to addition of mealtime pramlintide or rapid-acting insulin analogs. Curr Med Res Opin. 2010 May;26(5):1047-54. doi: 10.1185/03007991003634759.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: April 27, 2007
• First Submitted That Met QC Criteria: April 30, 2007
• First Posted (Estimate): May 1, 2007

Study Record Updates

• Last Update Posted (Estimate): April 14, 2015
• Last Update Submitted That Met QC Criteria: March 26, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: insulin; Amylin; Symlin; Novolog; Humalog; Apidra
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Pramlintide; Insulin Glargine; Insulin Lispro; Insulin glulisine; Insulin Detemir; Insulin, Short-Acting
• Other Study ID Numbers: ACA401