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Completed

NCT Number: NCT01275131

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

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.

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Key information

Conditions

Type 1 Diabetes Mellitus Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Profil Institute for Clinical Research

Chula Vista, California, 91911, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • 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.
  • Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m^2), inclusive.
  • Glycosylated hemoglobin A1c (HbA1c) ≤10 % based on local laboratory results.
  • Fasting C-peptide <0.6 nanograms per milliliter (ng/mL).
  • Current treatment with insulin <90 units per day (U/d).
  • Routine use of continuous subcutaneous insulin infusion (CSII) as the primary route of insulin administration.
  • 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

  • Known or suspected allergy to any component of any of the study drugs in this trial.
  • Previous enrollment in this trial (Exception: participants in Stage 1 are permitted to participate in Stage 2).
  • 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.
  • Use of any long-acting insulin injection within 72 hours of Stage 1 or Stage 3.
  • Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator.
  • Current addiction to alcohol or substances of abuse as determined by the Investigator.
  • 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.
  • 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).
  • Symptomatic gastroparesis.
  • Receipt of any investigational drug within 4 weeks of Stage 1 or Stage 2.

Treatment and study plan

insulin aspart

Drug

Other names: Novolog

Recombinant human hyaluronidase PH20 (rHuPH20)

Drug

Other names: PH20, Hylenex

Primary outcomes

  1. Early Insulin Exposure (%AUC[0-60]), Stage 1

    Time frame: 10 minutes predose up to 60 minutes postdose

    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.

  2. 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

    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.

Secondary outcomes

  1. Maximum Glucose Infusion Rate (GIRmax), Stage 1

    Time frame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8

    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.

  2. Maximum Glucose Infusion Rate (GIRmax), Stage 3

    Time frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10

    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.

  3. 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

    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.

  4. 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

    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.

  5. 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

    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.

  6. 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

    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.

  7. 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

    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.

  8. 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

    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.

  9. 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

    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.

  10. 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

    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.

  11. 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

    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.

  12. 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

    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.

Sponsors and collaborators

Lead sponsor

Halozyme Therapeutics

Industry

Registry information

Official study title

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)

Important dates

Study start
2011
Primary completion
2011
Study completion
2011
First posted
Jan 12, 2011
Registry last updated
Jul 25, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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