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A Study of Continuous Subcutaneous Insulin Infusion (CSII) Pump Function in Subjects With Type 1 Diabetes With Recombinant Human Hyaluronidase (rHuPH20) (HALO-117-406)

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ClinicalTrials.gov Identifier: NCT03662334
Recruitment Status : Completed
First Posted : September 7, 2018
Results First Posted : February 1, 2019
Last Update Posted : February 1, 2019
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics

Tracking Information
First Submitted Date  ICMJE August 13, 2018
First Posted Date  ICMJE September 7, 2018
Results First Submitted Date  ICMJE October 10, 2018
Results First Posted Date  ICMJE February 1, 2019
Last Update Posted Date February 1, 2019
Actual Study Start Date  ICMJE October 3, 2013
Actual Primary Completion Date February 27, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 30, 2019)
  • Part 1: Area Under the Curve (AUC) of Glucose Infusion Rate (GIR) From 0-6 Hours [ Time Frame: 0-6 hours ]
  • Part 2: Time to Reduction in Plasma Glucose by 80 Milligrams Per Deciliter (mg/dL) Following CSII Bolus [ Time Frame: 0-10 hours ]
    Time to reduction is reported as the maximum time it took for any participant receiving each treatment sequence to achieve a reduction in plasma glucose by 80 mg/dL. During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 mg/dL, even after adjusting several operational parameters. The study was stopped early, prior to enrolling the planned 24 participants for Part 2. Thus, analysis for this endpoint was not conducted. Raw data (as a maximum) are reported.
  • Part 3: Time to Achieve Plasma Glucose >90 mg/dL After Release of Hypoglycemic CSII Clamp [ Time Frame: 0-12 hours ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 5, 2018)
  • Part 1: Area Under the Curve (AUC) of Glucose Infusion Rate (GIR) From 0-6 Hours [ Time Frame: 0-6 hours ]
  • Part 2: Time to Reduction in Plasma Glucose by 80 Milligrams Per Deciliter (mg/dL) Following CSII Bolus [ Time Frame: 0-10 hours ]
  • Part 3: Time to Achieve Plasma Glucose >90 mg/dL After Release of Hypoglycemic CSII Clamp [ Time Frame: 0-12 hours ]
Change History Complete list of historical versions of study NCT03662334 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2019)
  • Part 1: Time-action Profile, Assessed by GIR in Euglycemic Participants [ Time Frame: up to approximately 10 hours ]
  • Part 1: Mean Maximum Concentration (Cmax) [ Time Frame: up to approximately 22 hours ]
  • Part 1: Time to Achieve Maximum Concentration (Tmax) [ Time Frame: up to approximately 22 hours ]
  • Part 1: Early Time to 50% Maximum Serum Insulin Concentration (t50%) Max [ Time Frame: up to approximately 22 hours ]
  • Part 1: Time to 50% of Total AUC (AUC0-last) [ Time Frame: up to approximately 22 hours ]
  • Part 1: Fractional and Absolute AUC0-1hr [ Time Frame: 0 to 1 hour ]
  • Part 1: Fractional and Absolute AUC2hr-end [ Time Frame: 2 to approximately 22 hours ]
  • Part 1: Area Under the Curve From Time Zero to the Last Measureable Concentration (AUC0-last) [ Time Frame: up to approximately 22 hours ]
  • Part 1: Mean Residence Time (MRT) [ Time Frame: up to approximately 22 hours ]
  • Part 2: Plasma Glucose Concentration Over Time [ Time Frame: up to approximately 10 hours ]
    Plasma glucose concentration over time is reported as the maximum concentration for any participant receiving each treatment sequence. During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 mg/dL, even after adjusting several operational parameters. The study was stopped early, prior to enrolling the planned 24 participants for Part 2. Thus, analysis for this endpoint was not conducted. Raw data (as a maximum) are reported.
  • Part 2: Insulin Analog Serum Concentration as a Function of Time Following Bolus Insulin Infusion [ Time Frame: up to approximately 10 hours ]
    Insulin analog serum concentration is reported as the maximum concentration for any participant receiving each treatment sequence. During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 mg/dL, even after adjusting several operational parameters. The study was stopped early, prior to enrolling the planned 24 participants for Part 2. Thus, analysis for this endpoint was not conducted. Raw data (as a maximum) are reported.
  • Part 3: Plasma Glucose Concentration Over Time [ Time Frame: up to approximately 12 hours ]
  • Part 3: Insulin Analog Serum Concentration as a Function of Time Following Termination of Insulin Infusion [ Time Frame: up to approximately 12 hours ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 5, 2018)
  • Part 1: Time-action Profile, Assessed by GIR in Euglycemic Participants [ Time Frame: up to approximately 10 hours ]
  • Part 1: Mean Maximum Concentration (Cmax) [ Time Frame: up to approximately 22 hours ]
  • Part 1: Time to Achieve Maximum Concentration (Tmax) [ Time Frame: up to approximately 22 hours ]
  • Part 1: Early Time to 50% Maximum Serum Insulin Concentration (t50%) Max [ Time Frame: up to approximately 22 hours ]
  • Part 1: Time to 50% of Total AUC (AUC0-last) [ Time Frame: up to approximately 22 hours ]
  • Part 1: Fractional and Absolute AUC0-1hr [ Time Frame: 0 to 1 hour ]
  • Part 1: Fractional and Absolute AUC2hr-end [ Time Frame: 2 to approximately 22 hours ]
  • Part 1: Area Under the Curve From Time Zero to the Last Measureable Concentration (AUC0-last) [ Time Frame: up to approximately 22 hours ]
  • Part 1: Mean Residence Time (MRT) [ Time Frame: up to approximately 22 hours ]
  • Part 2: Plasma Glucose Concentration Over Time [ Time Frame: up to approximately 10 hours ]
  • Part 2: Insulin Analog Serum Concentration as a Function of Time Following Bolus Insulin Infusion [ Time Frame: up to approximately 10 hours ]
  • Part 3: Plasma Glucose Concentration Over Time [ Time Frame: up to approximately 12 hours ]
  • Part 3: Insulin Analog Serum Concentration as a Function of Time Following Termination of Insulin Infusion [ Time Frame: up to approximately 12 hours ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Continuous Subcutaneous Insulin Infusion (CSII) Pump Function in Subjects With Type 1 Diabetes With Recombinant Human Hyaluronidase (rHuPH20)
Official Title  ICMJE A Phase 4, Double Blind, Single Center, Randomized, Cross-Over Study of Continuous Subcutaneous Insulin Infusion (CSII) Pump Functionality in Subjects With Type 1 Diabetes Comparing Pretreatment vs. No Pretreatment With Recombinant Human Hyaluronidase (rHuPH20)
Brief Summary The goal of this study is to determine if Hylenex recombinant leads to changes in the insulin time-action profiles and glucose responses when preadministered in the setting of continuous subcutaneous insulin infusion (CSII) compared to CSII without Hylenex recombinant (sham injection).
Detailed Description There is a recognized need for more rapid insulin action than is available from current rapid-acting analog products. In addition, current products have inconstant absorption and action profiles over the course of infusion set life. Previous human studies of prandial insulin preparations have used co-mixtures of rHuPH20 (study drug) with insulin delivered to study participants by subcutaneous injection and have demonstrated acceleration of insulin absorption and action. CSII has been used clinically for the treatment of diabetes over the last three decades, and a previous study using a co-mixture of rHuPH20 during CSII showed that the combination resulted in a more consistent and ultrafast profile of insulin absorption and action across infusion set use as compared to rapid analog insulin alone.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Type 1 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Rapid Acting insulin with pre-treatment of rHuPH20
    Hylenex recombinant will be administered via infusion sets and insulin pumps. These will be compatible with component tubing system attached to the insulin infusion site and will be placed in the lower abdominal area.
    Other Names:
    • Humalog
    • Hylenex
  • Device: Sham injection
    A sham injection will be administered via infusion sets and insulin pumps. These will be compatible with component tubing system attached to the insulin infusion site and will be placed in the lower abdominal area.
    Other Name: placebo
Study Arms  ICMJE
  • Experimental: Hylenex recombinant
    Comparing the preadministration of Hylenex recombinant in the setting of continuous subcutaneous insulin infusion (CSII).
    Intervention: Drug: Rapid Acting insulin with pre-treatment of rHuPH20
  • Sham Comparator: Sham Injection
    Comparing the preadministration of a sham injection in the setting of CSII.
    Intervention: Device: Sham injection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 5, 2018)
14
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 27, 2014
Actual Primary Completion Date February 27, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female participants between the ages 18 and 65 years, inclusive.
  2. Females of child-bearing potential must agree to use a standard and effective means of birth control for the duration of the study. Adequate contraceptive measures include oral or injectable contraceptives, sterilization, intra-uterine device (IUD), barrier methods, or abstinence.
  3. Participants with type 1 diabetes mellitus treated with insulin (multiple daily injections or continuous subcutaneous insulin infusion [CSII]) diagnosed ≥ 12 months prior to enrollment
  4. Body mass index (BMI) 18.0 to 32.0 kilograms per meters squared (kg/m^2)
  5. HbA1c (glycated hemoglobin A1c) ≤ 10% based on local laboratory results
  6. Fasting C-peptide < 0.6 nanograms per milliliter (ng/mL)
  7. Current treatment with insulin <1.2 Units per kg per day (U/kg/day)
  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 injections and assessments required in this protocol

Exclusion Criteria:

  1. Inability to comply with study requirements as judged by the Investigator
  2. Known or suspected allergy to any component of any of the study drugs in this trial
  3. A participant who has proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator
  4. As judged by the Investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on electrocardiogram), hepatic, neurological, renal, genitourinary, or hematological systems
  5. As judged by the Investigator, uncontrolled hypertension (diastolic blood pressure ≥ 100 millimeters of mercury [mmHg] and/or systolic blood pressure ≥ 160 mmHg after 5 minutes in the supine position)
  6. History of any illness or disease that in the opinion of the Investigator might confound the results of the trial or pose additional risk in administering the study drugs to the participant
  7. As judged by the Investigator, clinically significant findings in routine laboratory data. Anemia with hemoglobin less than lower limits of normal at screening is specifically exclusionary
  8. 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, or drugs not permitted according to Hylenex recombinant package insert
  9. Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator
  10. Current addiction to alcohol or substances of abuse as determined by the Investigator
  11. Blood donation (> 500 mL) within the previous 8 weeks (56 days) prior to Day -1 of Treatment Period 1
  12. Pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, IUD, oral or injectable contraceptives, or barrier methods)
  13. Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study
  14. Participation in any other clinical trial and receipt of any investigational drug within 4 weeks of Day -1 of Treatment Period 1
  15. Any condition (intrinsic or extrinsic) that in the judgment of the Investigator will interfere with trial participation or evaluation of data
  16. Positive for human immunodeficiency virus (HIV), Hepatitis C or Hepatitis B
  17. Tobacco and nicotine use within 3 months prior to Day 1 of Treatment Period 1 or use during the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03662334
Other Study ID Numbers  ICMJE HALO-117-406
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Halozyme Therapeutics
Study Sponsor  ICMJE Halozyme Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Halozyme Therapeutics
Verification Date January 2019

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