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

Primary Purpose

Diabetes Mellitus, Type 1

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Insulin lispro
recombinant human hyaluronidase PH20
Insulin aspart
Insulin glulisine
Insulin glargine
Sponsored by
Halozyme Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Type 1 diabetes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • AMCR Institute, Inc.
  • Scripps Whittier Diabetes Institute
  • Mills-Peninsula Health Services
  • Barbara Davis Center for Childhood Diabetes
  • Center for Diabetes and Endocrine Care
  • Diabetes Research Institute
  • Rocky Mountain Diabetes and Osteoporosis Center
  • Mid-America Diabetes Associates
  • Tulane University Health Sciences Center
  • Medstar Research Institute
  • Henry Ford Health System
  • International Diabetes Center
  • Mercury Street Medical
  • Desert Endocrinology
  • UT Southwestern Medical Center at Dallas
  • Texas Diabetes and Endocrinology
  • Cetero Research-San Antonio
  • West Olympia Internal Medicine
  • University of Washington School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Lispro-PH20 / Insulin Lispro

Aspart-PH20 / Insulin Lispro

Arm Description

All enrolled participants underwent a titration period of 4-6 weeks in which they received 100 units per milliliter (U/mL) insulin glulisine, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually. Next participants were randomly assigned to 1 of 2 study treatments (Treatment A or B) for the first of two, 3-month treatment cycles. Each participant then received the second treatment for the second cycle with no washout period. Lispro-PH20 (Treatment A): 100 U/mL insulin lispro with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, with doses titrated to each participant individually Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

All enrolled participants underwent a titration period of 4-6 weeks in which they received 100 units per milliliter (U/mL) insulin glulisine, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually. Next participants were randomly assigned to 1 of 2 study treatments (Treatment A or B) for the first of two, 3-month treatment cycles. Each participant then received the second treatment for the second cycle with no washout period. Aspart-PH20 (Treatment A): 100 U/mL insulin aspart with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, with doses titrated to each participant individually Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
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).
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.
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).
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.

Full Information

First Posted
August 31, 2010
Last Updated
February 5, 2019
Sponsor
Halozyme Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT01194245
Brief Title
Safety/Efficacy Study of Subcutaneously Injected Prandial Insulins Compared to Insulin Lispro Alone in Participants With Type 1 Diabetes Mellitus
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Halozyme Therapeutics

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
Keywords
Type 1 diabetes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
135 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lispro-PH20 / Insulin Lispro
Arm Type
Experimental
Arm Description
All enrolled participants underwent a titration period of 4-6 weeks in which they received 100 units per milliliter (U/mL) insulin glulisine, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually. Next participants were randomly assigned to 1 of 2 study treatments (Treatment A or B) for the first of two, 3-month treatment cycles. Each participant then received the second treatment for the second cycle with no washout period. Lispro-PH20 (Treatment A): 100 U/mL insulin lispro with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, with doses titrated to each participant individually Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.
Arm Title
Aspart-PH20 / Insulin Lispro
Arm Type
Experimental
Arm Description
All enrolled participants underwent a titration period of 4-6 weeks in which they received 100 units per milliliter (U/mL) insulin glulisine, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually. Next participants were randomly assigned to 1 of 2 study treatments (Treatment A or B) for the first of two, 3-month treatment cycles. Each participant then received the second treatment for the second cycle with no washout period. Aspart-PH20 (Treatment A): 100 U/mL insulin aspart with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, with doses titrated to each participant individually Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.
Intervention Type
Drug
Intervention Name(s)
Insulin lispro
Other Intervention Name(s)
Humalog
Intervention Type
Drug
Intervention Name(s)
recombinant human hyaluronidase PH20
Other Intervention Name(s)
Hylenex, rHuPH20, PH20
Intervention Type
Drug
Intervention Name(s)
Insulin aspart
Intervention Type
Drug
Intervention Name(s)
Insulin glulisine
Other Intervention Name(s)
Apidra
Intervention Type
Drug
Intervention Name(s)
Insulin glargine
Other Intervention Name(s)
Lantus
Primary Outcome Measure Information:
Title
Change From Baseline in Glycosylated Hemoglobin A1C (HbA1c) at the End of Each Treatment Period
Description
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.
Time Frame
Baseline, Week 12 and Week 24
Secondary Outcome Measure Information:
Title
Mean Daily Insulin Dose
Description
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).
Time Frame
Week 10 and Week 22
Title
Percentage of Participants Meeting Glucose Targets
Description
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).
Time Frame
Baseline through Week 24, excluding 10-point glucose monitoring days
Title
Rates of Hypoglycemia at the End of Each Treatment Period
Description
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.
Time Frame
Week 12 and Week 24
Title
Change From Baseline in Body Weight at the End of Each Treatment Period
Description
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).
Time Frame
Baseline, Week 12 and Week 24
Title
Mean Daily Postprandial Glucose (PPG) Excursions
Description
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.
Time Frame
Week 10 and Week 22

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Douglas Muchmore, M.D.
Organizational Affiliation
Halozyme Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
AMCR Institute, Inc.
City
Escondido
State/Province
California
ZIP/Postal Code
92026
Country
United States
Facility Name
Scripps Whittier Diabetes Institute
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Mills-Peninsula Health Services
City
San Mateo
State/Province
California
ZIP/Postal Code
94401
Country
United States
Facility Name
Barbara Davis Center for Childhood Diabetes
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Center for Diabetes and Endocrine Care
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Diabetes Research Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Rocky Mountain Diabetes and Osteoporosis Center
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
Mid-America Diabetes Associates
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67211
Country
United States
Facility Name
Tulane University Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Medstar Research Institute
City
Hyattsville
State/Province
Maryland
ZIP/Postal Code
20782
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
International Diabetes Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55416
Country
United States
Facility Name
Mercury Street Medical
City
Butte
State/Province
Montana
ZIP/Postal Code
59701
Country
United States
Facility Name
Desert Endocrinology
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89052
Country
United States
Facility Name
UT Southwestern Medical Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Texas Diabetes and Endocrinology
City
Round Rock
State/Province
Texas
ZIP/Postal Code
78681
Country
United States
Facility Name
Cetero Research-San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
West Olympia Internal Medicine
City
Olympia
State/Province
Washington
ZIP/Postal Code
98502
Country
United States
Facility Name
University of Washington School of Medicine
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

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

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