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Randomized, Double-blind, Crossover, Pharmacokinetic (PK) and Glucodynamic (GD) Study of Continuous Subcutaneous Insulin Infusion (CSII) in Participants With Type 1 Diabetes Mellitus (T1DM)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT01275131
First received: January 10, 2011
Last updated: June 26, 2014
Last verified: June 2014

January 10, 2011
June 26, 2014
January 2011
December 2011   (final data collection date for primary outcome measure)
  • Early Insulin Exposure (%AUC[0-60]), Stage 1 [ Time Frame: 10 minutes predose up to 60 minutes postdose ] [ Designated as safety issue: No ]
    Early insulin exposure, defined as the percentage of total insulin exposure (area under the insulin concentration curve [AUC{0-360}]) that occurs within the first hour following bolus dose of insulin during the 2 euglycemic clamps is presented. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 120, 150, 180, 240, 300, and 360 minutes postdose during the euglycemic clamp.
  • Early Exposure to Insulin (%AUC[0-60]), Stage 3 [ Time Frame: 10 minutes predose up to 60 minutes postdose on Days 2/7, 3/8, and 5/10 ] [ Designated as safety issue: No ]
    Early insulin exposure, defined as the percentage of total insulin exposure (area under the insulin concentration curve [AUC{0-360}) that occurs within the first hour following bolus dose of insulin during the 2 euglycemic clamps is presented. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 120, 150, 180, 240, 300, and 360 minutes postdose during the euglycemic clamp.
Pharmacokinetic percent of area under the curve [ Time Frame: 0 to 60 minutes ] [ Designated as safety issue: No ]
Based on serum insulin concentrations collected at specified time points, compare PK %AUC0-60 for insulin analogs with and without rHuPH20.
Complete list of historical versions of study NCT01275131 on ClinicalTrials.gov Archive Site
  • Maximum Glucose Infusion Rate (GIRmax), Stage 1 [ Time Frame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8 ] [ Designated as safety issue: No ]
    Maximum glucose infusion rates (GIRmax) for Stage1 are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.
  • Maximum Glucose Infusion Rate (GIRmax), Stage 3 [ Time Frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10 ] [ Designated as safety issue: Yes ]
    Maximum glucose infusion rates (GIRmax) for Stage 3 are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.
  • Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 1 [ Time Frame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8 ] [ Designated as safety issue: No ]
    Time to first occurrence of maximum glucose infusion rate (tGIRmax) for Stage 1 is presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.
  • Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 3 [ Time Frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10 ] [ Designated as safety issue: No ]
    Time to first occurrence of maximum glucose infusion rate (tGIRmax) for Stage 3 is presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.
  • Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 1 [ Time Frame: 0 up to 360 minutes postdose on day 2/6 and Day 4/8 ] [ Designated as safety issue: No ]
    Early and late times to 50% maximum glucose infusion rate (tGIR50%max) for Stage 1 are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.
  • Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 3 [ Time Frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10 ] [ Designated as safety issue: No ]
    Early and late time to 50% maximum glucose infusion rates (tGIR50%max) for Stage 3 studies are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.
  • Time to 50% Total Glucose Infused (50%Gtot), Stage 1 [ Time Frame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8 ] [ Designated as safety issue: No ]
    Time to 50% total glucose infused (50%Gtot) is presented for Stage 1. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.
  • Time to 50% Total Glucose Infused (50%Gtot), Stage 3 [ Time Frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10 ] [ Designated as safety issue: Yes ]
    Time to 50% of total glucose infused (50%Gtot) is presented for Stage 3. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.
  • Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 1 [ Time Frame: 30 minutes predose up to 360 minutes postdose on Day 2/6 and Day 4/8 ] [ Designated as safety issue: No ]
    Area under the glucose concentration curve for 0 to 360 minutes (AUC[0-360]) from Stage 1 is presented. Blood samples were collected 30 and 10 minutes prior to insulin bolus and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.
  • Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 3 [ Time Frame: 30 minutes predose up to 360 minutes postdose Days 2/7, 3/8, and 5/10 ] [ Designated as safety issue: No ]
    Area under the glucose concentration curve from 0 to 360 minutes (AUC[0-360]) for Stage 3 studies is presented. Blood samples were collected 30 and 10 minutes prior to insulin bolus and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.
  • Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 1 [ Time Frame: 10 minutes predose up to 360 minutes postdose on Day 2/6 and Day 4/8 ] [ Designated as safety issue: No ]
    Duration of insulin action was calculated by dividing the area under the first moment curve (AUMC[0-360]) by the area under the concentration versus time curve (AUC[0-360]) for Stage 1. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.
  • Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 3 [ Time Frame: 10 minutes predose up to 360 minutes postdose on Days 2/7, 3/8, and 5/10 ] [ Designated as safety issue: No ]
    Duration of insulin action was calculated by dividing the area under the first moment curve (AUMC[0-360]) by the area under the concentration versus time curve (AUC[0-360]) for Stage 3. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.
Determine and compare glucodynamic responses [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
Determine and compare various GD responses (including tmax, Early and Late tGIR50%max, GIRmax, time to various % of total glucose infused increments, and fractional and absolute total glucose infused at various time intervals), based on glucose infusion rates over time for each study treatment.
Not Provided
Not Provided
 
Randomized, Double-blind, Crossover, Pharmacokinetic (PK) and Glucodynamic (GD) Study of Continuous Subcutaneous Insulin Infusion (CSII) in Participants With Type 1 Diabetes Mellitus (T1DM)
Randomized, Double-Blind, Pharmacokinetic (PK) and Glucodynamic (GD) Crossover Study of Continuous Subcutaneous Insulin Infusion (CSII) of Rapid Acting Insulin Analogs With and Without Recombinant Human Hyaluronidase (rHuPH20)

The purpose of this study is to determine if recombinant human hyaluronidase PH20 (rHuPH20) will change the exposure and action of approved insulin analogs when given by continuous subcutaneous insulin infusion (CSII) in participants with Type 1 diabetes mellitus (T1DM).

This study is divided into Stage 1, 2, and 3. Stage 3 was started chronologically before Stage 2 and, prior to performing Stage 2, the Sponsor made the decision to terminate Stage 2. Stage 2 was not initiated due to a strategic business decision and termination was not based on safety or efficacy concerns. No participants were enrolled in Stage 2.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Type 1 Diabetes Mellitus
  • Drug: Insulin aspart
    Other Name: Novolog
  • Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
    Other Names:
    • PH20
    • Hylenex
  • Active Comparator: Stage 1: Insulin aspart first, then insulin aspart-rHuPH20

    Participants first received 0.15 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4.

    After a 5- to 14-day washout period, participants received 0.15 U/kg insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) coadministered as a CSII, for 4 days (Days 5-8; Period 2), including during a 6-hr euglycemic clamp on Days 6 and 8.

    Interventions:
    • Drug: Insulin aspart
    • Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
  • Active Comparator: Stage 1: Insulin aspart-rHuPH20 first, then insulin aspart

    Participants first received 0.15 units per kilogram (U/kg) insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) coadministered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4.

    After a 5- to 14-day washout period, participants received 0.15 U/kg insulin aspart alone as a CSII, for 4 days (Days 5-8; Period 2), including during a 6-hr euglycemic clamp on Days 6 and 8.

    Interventions:
    • Drug: Insulin aspart
    • Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
  • Active Comparator: Stage 3: Insulin aspart first, then insulin aspart + rHuPH20

    Participants first received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5. On Day 2 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp.

    After a 5- to 14-day washout period, participants received 0.12 U/kg insulin aspart administered as a CSII, for 5 days (Days 6-10; Period 2), including during a 6-hr euglycemic clamp on Days 7, 8, and 10. On Day 7 only, a 1.0-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the 6-hr euglycemic clamp.

    Interventions:
    • Drug: Insulin aspart
    • Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
  • Active Comparator: Stage 3: Insulin aspart + rHuPH20 first, then insulin aspart

    Participants first received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5; Period 1), including during a 6- hour (hr) euglycemic clamp on Days 2, 3, and 5. On Day 2 only, a 1.0-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the euglycemic clamp .

    After a 5- to 14- day washout period, participants received 0.12 U/kg insulin aspart administered as a CSII, for 5 days (Days 6-10; Period 2), including during a 6-hr euglycemic clamp on Days 7, 8, and 10. On Day 7 only, a sham injection was administered 2.5 hr prior to the 6-hour euglycemic clamp.

    Interventions:
    • Drug: Insulin aspart
    • Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
45
December 2011
December 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Male or female aged 18 to 65 years, inclusive. Females of child-bearing potential must use a standard and effective means of birth control for the duration of the study.
  2. Non-smoking participants with Type 1 diabetes mellitus (T1DM) treated with insulin for greater than or equal to 12 months. Non-smoking means abstinence from cigarettes and cigars for 3 months and negative cotinine screening tests.
  3. Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m^2), inclusive.
  4. Glycosylated hemoglobin A1c (HbA1c) ≤10 % based on local laboratory results.
  5. Fasting C-peptide <0.6 nanograms per milliliter (ng/mL).
  6. Current treatment with insulin <90 units per day (U/d).
  7. Routine use of continuous subcutaneous insulin infusion (CSII) as the primary route of insulin administration.
  8. Participant should be in good general health based on medical history and physical examination, without medical conditions that might prevent the completion of study drug infusions and assessments required in this protocol.

Exclusion Criteria:

  1. Known or suspected allergy to any component of any of the study drugs in this trial.
  2. Previous enrollment in this trial (Exception: participants in Stage 1 are permitted to participate in Stage 2).
  3. Use of drugs that may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia. Participants taking maintenance doses of blood thinners (eg, Coumadin or heparin) will be excluded.
  4. Use of any long-acting insulin injection within 72 hours of Stage 1 or Stage 3.
  5. Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator.
  6. Current addiction to alcohol or substances of abuse as determined by the Investigator.
  7. Blood donation or phlebotomy (>500 milliliters [mL]) within the previous 8 weeks of Screening. This applies both to new participants and to participants who have participated in Stage 1 and who wish to continue in Stage 2.
  8. Pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, intra-uterine device [IUD], oral or injectable contraceptives, or barrier methods).
  9. Symptomatic gastroparesis.
  10. Receipt of any investigational drug within 4 weeks of Stage 1 or Stage 2.
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01275131
HALO-117-105
No
Halozyme Therapeutics
Halozyme Therapeutics
Not Provided
Principal Investigator: Linda Morrow, MD Profil Institute for Clinical Research, Inc.
Halozyme Therapeutics
June 2014

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