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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT01194245
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 ]
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.
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 NCT01194245 on ClinicalTrials.gov Archive Site
  • Mean Daily Insulin Dose [ Time Frame: Week 10 and Week 22 ] [ Designated as safety issue: No ]
    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 [ 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 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 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
    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 [ 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 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.
  • 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: No ]
  • 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 Participants With Type 1 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 1 Diabetes

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.

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.

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 1
  • Drug: Insulin lispro
    Other Name: Humalog
  • Drug: recombinant human hyaluronidase PH20
    Other Names:
    • Hylenex
    • rHuPH20
    • PH20
  • Drug: Insulin aspart
  • 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 4-6 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.

    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 4-6 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.

    Interventions:
    • Drug: Insulin lispro
    • Drug: recombinant human hyaluronidase PH20
    • Drug: Insulin aspart
    • 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
135
August 2011
August 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01194245
HALO-117-205
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