Safety/Efficacy Study of Subcutaneously Injected Prandial Insulins Compared to Insulin Lispro Alone in Patients With Type 2 Diabetes Mellitus

Diabetes Mellitus, Type II Clinical Trial

Official title:

A Phase II, Randomized, Double Blind, 2-Way Crossover Safety and Efficacy Study of Subcutaneously Injected Prandial Insulins: Lispro-PH20 or Aspart-PH20 Compared to Insulin Lispro (Humalog®) in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01194258
• Other study ID #: HALO-117-206
• Status: Completed
• Phase: Phase 2
• First received: August 31, 2010
• Last updated: August 1, 2014
• Start date: August 2010
• Est. completion date: August 2011

Study information

• Verified date: August 2014
• Source: Halozyme Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the study was to compare Humalog (insulin lispro)-recombinant human hyaluronidase PH20 (rHuPH20) or Novolog (insulin aspart)-rHuPH20 to insulin lispro for the treatment of Type 2 diabetes mellitus (T2DM) in basal-bolus therapy.

Description:

Criteria for randomization into the study included 1) fasting blood glucose and pre-dinner glucose values in the range of 70 to 140 milligrams per deciliter (mg/dL) approximately 60% of the time for 7 days prior to randomization; 2) 90 minute or 2-hour postprandial blood glucose <220 mg/dL approximately 70% of the time for 7 days prior to randomization; and 3) successfully completing 3 days of 10-point glucose monitoring and have at least 4 self-monitored blood glucose values on all non-10-point monitoring days. Participants that did not meet 1 or more of these criteria during a 4- to 6-week Titration Period were not randomized.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Males or females =18 years

• Type 2 diabetes mellitus (T2DM) treated with insulin =12 months and prandial insulin (at least 2 meals per day) for =2 months

• Body mass index (BMI) of 23.0 to 45.0 kilograms per meter squared (kg/m^2)

• Glycosylated hemoglobin (HbA1C) level 7.0 to 8.5%, inclusive

• Fasting C-peptide <0.6 nanograms per milliliter (ng/mL)

• Willingness to use insulin glargine twice a day as basal insulin for the duration of the study

• Willingness to avoid use of an insulin infusion pump or unblinded continuous glucose monitoring (CGM) during the study

Exclusion Criteria:

• Known or suspected allergy to any component of any of the study drugs

• Exclusive use of pre-mixed insulins

• Use of pramlintide, exenatide, and/or liraglutide within 30 days of screening

• Use of sulfonylureas within two months of screening

• Use of drugs (such as corticosteroids or antimetabolites) that could interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia, during the study or within 30 days of screening

• Recurrent severe hypoglycemia (more than 2 episodes over the last 6 months) or hypoglycemic unawareness, as judged by the investigator

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetes Mellitus, Type II

Intervention

Drug:
• Insulin lispro

• Insulin aspart

• Recombinant human hyaluronidase PH20

• Insulin glulisine

• Insulin glargine

Locations

Country	Name	City	State
United States	Mercury Street Medical	Butte	Montana
United States	John Muir Physician Network Clinical Research Center	Concord	California
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Medical Group of Encino	Encino	California
United States	AMCR Institute, Inc.	Escondido	California
United States	Marin Endocrine Care and Research	Greenbrae	California
United States	Desert Endocrinology	Henderson	Nevada
United States	Center for Diabetes and Endocrine Care	Hollywood	Florida
United States	Medstar Research Institute	Hyattsville	Maryland
United States	Rocky Mountain Diabetes and Osteoporosis Center	Idaho Falls	Idaho
United States	Baptist Diabetes Associates	Miami	Florida
United States	Diabetes Research Institute	Miami	Florida
United States	International Diabetes Center	Minneapolis	Minnesota
United States	Diabetes and Endocrinology Associates, PC	Morehead	North Carolina
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	West Olympia Internal Medicine	Olympia	Washington
United States	Texas Diabetes and Endocrinology	Round Rock	Texas
United States	Cetero Research-San Antonio	San Antonio	Texas
United States	Mills-Peninsula Health Services	San Mateo	California
United States	University of Washington School of Medicine	Seattle	Washington
United States	Mid-America Diabetes Associates	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Halozyme Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Glycosylated Hemoglobin A1C (HbA1C) at the End of Each Treatment Period	Change in glycosylated hemoglobin A1C (HbA1C) from baseline (Week 0) to end of treatment period (Week 12 and Week 24) is presented. Data are presented by combined treatment group (Lispro-recombinant human hyaluronidase PH20 (PH20) + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin lispro from both groups). Least squares (LS) means were calculated from linear contrasts of mixed effects linear models with treatment (Lispro, Aspart), PH20 (yes, no), and treatment sequence as fixed effects and participant within treatment sequence as a random effect.	Baseline, Week 12 and Week 24	No
Secondary	Mean Daily Insulin Dose as Recorded During 10-Point Glucose Monitoring	Mean daily insulin dose as recorded during 10-point glucose monitoring is reported. Blood glucose values were obtained during a total of 3 days during each treatment period (3 days during Week 10 of Treatment Period 1 and 3 days during Week 22 of Treatment Period 2) at the following timepoints: immediately prior to breakfast (fasting), 1 hour (hr) after breakfast, 2 hr after breakfast, immediately prior to lunch, 1 hr after lunch, 2 hr after lunch, immediately prior to dinner, 1 hr after dinner, 2 hr after dinner, and at 03:00. A minimum of 7 determinations were required for each day during the 3 days of 10-point glucose profiles. Prandial insulin doses were also recorded during the 10-point glucose monitoring and the mean daily insulin dose over the 3 days was calculated. Data are presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin Lispro from both cohorts).	Week 10 and Week 22	No
Secondary	Percentage of Participants Meeting Glucose Targets at Least 2/3 of the Time	Participants were instructed to monitor their blood glucose levels a minimum of 4 times per day on all non-10-point glucose monitoring days. The number of participants meeting 90-minute postprandial plasma glucose (PPG) targets of <140 and <180 milligrams per deciliter (mg/dL) for at least 2/3 of values was recorded during non-10-point glucose monitoring was recorded. The number of participants was recorded, and the percentage of participants meeting glucose targets was calculated by the number of participants with values meeting the specified target at least 2/3 of the time by the total number of participants analyzed, multiplied by 100. Data is presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin Lispro from both cohorts).	Baseline through Week 24, excluding 10-point glucose monitoring days	No
Secondary	Rates of Hypoglycemia at the End of Each Treatment Period	The rate of hypoglycemia, defined as blood glucose levels =70 mg/dL and <56 mg/dL, was calculated based on 4 weeks of observation prior to the end of treatment period (that is, Week 12 and Week 24). Data are presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin lispro from both groups). A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.	Week 12 and Week 24	No
Secondary	Change From Baseline in Body Weight at the End of Each Treatment Period	Change from baseline in body weight at the end of each treatment period (Week 12 and Week 24) is presented. Data are presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin lispro from both cohorts).	Baseline, Week 12 and Week 24	Yes
Secondary	Mean Daily PPG Excursions	Participants performed 10-point glucose monitoring for a total of 3 days during each treatment period (3 days during Week 10 of Treatment Period 1 and 3 days during Week 22 of Treatment Period 2). Mean daily PPG excursions during 10-point glucose monitoring for breakfast, lunch, and dinner from Treatment Period 1 or Treatment Period 2 are presented. PPG refers to the change in glucose concentration before to after a meal. Data were collected 1 and 2 hours (hr) after each meal. Data are presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (insulin lispro from both cohorts).	Week 10 and Week 22	No