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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT01194258
First received: August 31, 2010
Last updated: August 1, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type II
Drug: Insulin lispro
Drug: Insulin aspart
Drug: Recombinant human hyaluronidase PH20
Drug: Insulin glulisine
Drug: Insulin glargine
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Halozyme Therapeutics:

Primary Outcome Measures:
  • Change From Baseline in Glycosylated Hemoglobin A1C (HbA1C) at the End of Each Treatment Period [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean Daily Insulin Dose as Recorded During 10-Point Glucose Monitoring [ Time Frame: Week 10 and Week 22 ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants Meeting Glucose Targets at Least 2/3 of the Time [ Time Frame: Baseline through Week 24, excluding 10-point glucose monitoring days ] [ Designated as safety issue: No ]
    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).

  • Rates of Hypoglycemia at the End of Each Treatment Period [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Body Weight at the End of Each Treatment Period [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: Yes ]
    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).

  • Mean Daily PPG Excursions [ Time Frame: Week 10 and Week 22 ] [ Designated as safety issue: No ]
    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).


Enrollment: 132
Study Start Date: August 2010
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lispro-PH20/Insulin lispro

All enrolled participants underwent a titration period of 4 to 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.

Lispro-PH20 (Treatment A): 100 U/mL insulin lispro with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (combined: Lispro-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.

Drug: Insulin lispro
Other Names:
  • Lispro
  • Humalog
Drug: Recombinant human hyaluronidase PH20
Other Names:
  • rHuPH20
  • PH20
  • Hylenex
Drug: Insulin glulisine
Other Name: Apidra
Drug: Insulin glargine
Other Name: Lantus
Experimental: Aspart-PH20/Insulin Lispro

All enrolled participants underwent a titration period of 4 to 6 weeks in which they received 100 U/mL insulin glulisine, injected 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.

Aspart-PH20 (Treatment A): 100 U/mL insulin aspart with 5.0 µg/mL rHuPH20 (combined: Aspart-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.

Drug: Insulin lispro
Other Names:
  • Lispro
  • Humalog
Drug: Insulin aspart
Other Names:
  • Aspart
  • Novolog
Drug: Recombinant human hyaluronidase PH20
Other Names:
  • rHuPH20
  • PH20
  • Hylenex
Drug: Insulin glulisine
Other Name: Apidra
Drug: Insulin glargine
Other Name: Lantus

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194258

Locations
United States, California
John Muir Physician Network Clinical Research Center
Concord, California, United States, 94520
Medical Group of Encino
Encino, California, United States, 91436
AMCR Institute, Inc.
Escondido, California, United States, 92026
Marin Endocrine Care and Research
Greenbrae, California, United States, 94904
Mills-Peninsula Health Services
San Mateo, California, United States, 94401
United States, Florida
Center for Diabetes and Endocrine Care
Hollywood, Florida, United States, 33021
Baptist Diabetes Associates
Miami, Florida, United States, 33156
Diabetes Research Institute
Miami, Florida, United States, 33136
United States, Idaho
Rocky Mountain Diabetes and Osteoporosis Center
Idaho Falls, Idaho, United States, 83404
United States, Kansas
Mid-America Diabetes Associates
Wichita, Kansas, United States, 67211
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
Medstar Research Institute
Hyattsville, Maryland, United States, 20782
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Minnesota
International Diabetes Center
Minneapolis, Minnesota, United States, 55416
United States, Montana
Mercury Street Medical
Butte, Montana, United States, 59701
United States, Nevada
Desert Endocrinology
Henderson, Nevada, United States, 89052
United States, North Carolina
Diabetes and Endocrinology Associates, PC
Morehead, North Carolina, United States, 28557
United States, Texas
UT Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390
Texas Diabetes and Endocrinology
Round Rock, Texas, United States, 78681
Cetero Research-San Antonio
San Antonio, Texas, United States, 78229
United States, Washington
West Olympia Internal Medicine
Olympia, Washington, United States, 98502
University of Washington School of Medicine
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Halozyme Therapeutics
Investigators
Study Director: Douglas Muchmore, M.D. Halozyme Therapeutics
  More Information

No publications provided

Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT01194258     History of Changes
Other Study ID Numbers: HALO-117-206
Study First Received: August 31, 2010
Results First Received: August 1, 2014
Last Updated: August 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Halozyme Therapeutics:
Type 2 diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glargine
Insulin
Insulin Aspart
Insulin glulisine
Insulin Lispro
Insulin, Globin Zinc
Insulin, Long-Acting
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014