Safety/Efficacy Study of Subcutaneously Injected Prandial Insulins Compared to Insulin Lispro Alone in Participants With Type 1 Diabetes Mellitus

Diabetes Mellitus, Type 1 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 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01194245
• Other study ID #: HALO-117-205
• Status: Completed
• Phase: Phase 2
• Start date: August 2010
• Est. completion date: August 2011

Study information

• Verified date: February 2019
• Source: Halozyme Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to compare Humalog (Insulin lispro)-recombinant human hyaluronidase (rHuPH20) or Novolog (Insulin aspart)-rHuPH20 to Humalog (Insulin lispro) for the treatment of Type 1 Diabetes Mellitus (T1DM) in basal-bolus therapy.

Description:

Criteria for randomization into the study included 1) fasting blood glucose and predinner 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 completed 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: 135
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Males or females aged =18 years

• Type 1 Diabetes Mellitus (T1DM) treated with insulin for =12 months

• Body mass index (BMI) 18.0 to 40.0 kilograms per square meter (kg/m^2).

• Hemoglobin A1C (HbA1C) level 6.7% to 8.2%, inclusive

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

• Willingness to use twice daily (BID) insulin glargine 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

• Use of pramlintide within 30 days of Screening

• Use of drugs during the study or within 30 days of Screening (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

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Drug:
• Insulin lispro

• recombinant human hyaluronidase PH20

• Insulin aspart

• Insulin glulisine

• Insulin glargine

Locations

Country	Name	City	State
United States	Barbara Davis Center for Childhood Diabetes	Aurora	Colorado
United States	Mercury Street Medical	Butte	Montana
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	AMCR Institute, Inc.	Escondido	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	Scripps Whittier Diabetes Institute	La Jolla	California
United States	Diabetes Research Institute	Miami	Florida
United States	International Diabetes Center	Minneapolis	Minnesota
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	Glycosylated hemoglobin A1C (HBA1c) levels were measured at baseline (Week 0) and at the end of each treatment period (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 cohorts). Least Squares (LS) means were calculated from mixed effects linear models with treatment (Lispro, Aspart), recombinant human hyaluronidase PH20 (rHuPH20; yes, no), and treatment sequence as fixed effects and participant within treatment sequence as a random effect.	Baseline, Week 12 and Week 24
Secondary	Mean Daily Insulin Dose	Prandial insulin doses were recorded during 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). The mean daily insulin dose over the 3 days during each treatment period is presented. Data is 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
Secondary	Percentage of Participants Meeting Glucose Targets	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 during non-10-point glucose monitoring days was recorded. The percentage was calculated by dividing 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
Secondary	Rates of Hypoglycemia at the End of Each Treatment Period	Overall rates of hypoglycemia (blood glucose =70 milligrams per deciliter [mg/dL] and <56 mg/dL) were calculated based on 4 weeks of observation for each treatment period. Data is presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin Lispro from both cohorts). 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
Secondary	Change From Baseline in Body Weight at the End of Each Treatment Period	Body weight was measured at baseline (Week 0) and at the end of each treatment period (Week 12 and Week 24). Data is 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
Secondary	Mean Daily Postprandial Glucose (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 postprandial plasma glucose (PPG) excursions (referring to the change in blood glucose levels from before to after a meal) during 10-point glucose monitoring for breakfast, lunch, and dinner are presented. Data were collected 1 and 2 hours (hr) after each meal for 3 days and the means of each excursion are presented.	Week 10 and Week 22