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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

August 31, 2010
August 1, 2014
August 2010
August 2011   (final data collection date for primary outcome measure)
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.
Change in A1C at the end of each treatment period from A1C at randomization. [ Time Frame: Screening, Baseline (week 0), week 12, week 24 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01194258 on ClinicalTrials.gov Archive Site
  • 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).
  • Rates of hypoglycemia [ Time Frame: Week 12 of treatment ] [ Designated as safety issue: No ]
    Rate calculated based on 4 weeks of observation
  • Insulin dose [ Time Frame: Week 12 of treatment ] [ Designated as safety issue: No ]
  • Weight change [ Time Frame: Week 12 of treatment ] [ Designated as safety issue: Yes ]
  • Blood glucose measures [ Time Frame: Week 12 of treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety/Efficacy Study of Subcutaneously Injected Prandial Insulins Compared to Insulin Lispro Alone in Patients With Type 2 Diabetes Mellitus
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Diabetes Mellitus, Type II
  • 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
  • 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.

    Interventions:
    • Drug: Insulin lispro
    • Drug: Recombinant human hyaluronidase PH20
    • Drug: Insulin glulisine
    • Drug: Insulin glargine
  • 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.

    Interventions:
    • Drug: Insulin lispro
    • Drug: Insulin aspart
    • Drug: Recombinant human hyaluronidase PH20
    • Drug: Insulin glulisine
    • Drug: Insulin glargine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
132
August 2011
August 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01194258
HALO-117-206
No
Halozyme Therapeutics
Halozyme Therapeutics
Not Provided
Study Director: Douglas Muchmore, M.D. Halozyme Therapeutics
Halozyme Therapeutics
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP