Randomized, Double Blind, 2 Way Crossover Study of CSII With, Versus Without, Pretreatment With Human Hyaluronidase

NCT01526733 | Completed Phase 4 Results

• 1 other identifier: Halo-117-401
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate consistency of accelerated insulin absorption and onset-of-action and shortened duration of action for bolus insulin infusions after pretreatment with 150 units (U) of Hylenex® (recombinant human hyaluronidase PH20 \[rHuPH20\]) injection at the time of infusion set insertion compared to sham injection.

Conditions

Type 1 Diabetes Mellitus

Keywords

Type 1 Diabetes; Continuous Subcutaneous Insulin Infusion (CSII)

Outcome Measures

Primary Outcomes (1)

• Early Insulin Exposure (%AUC[0-60])

  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, and 60 minutes postdose during a euglycemic clamp.

  10 minutes predose; 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose on Days 1 and 4

Secondary Outcomes (6)

• Maximum Glucose Infusion Rate (GIRmax)

  0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

• Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax)

  0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

• Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max)

  0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

• Time to 50% Total Glucose Infused (50%Gtot)

  0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

• Area Under the Glucose Concentration Curve (AUC[0-360])

  30 minutes and 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

Study Arms (2)

Insulin (Aspart or Lispro)-Sham

SHAM COMPARATOR

In Phase I or Phase II of the study, participants received 0.15 units per kilogram (U/kg) insulin (either insulin aspart or insulin lispro) as a continuous subcutaneous insulin infusion (CSII) for 16 days, with sham injections administered prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16. Each Phase was separated by a washout period of 5 to 21 days.

Drug: Sham Injection; Drug: Insulin aspart; Drug: Insulin lispro

Insulin (Aspart or Lispro)-rHuPH20

EXPERIMENTAL

In Phase I or Phase II of the study, participants received 0.15 U/kg insulin (either insulin aspart or insulin lispro) as a CSII for 16 days. Prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16, participants received a 1 mL (150 U) injection of recombinant human hyaluronidase (rHuPH20). Each Phase was separated by a washout period of 5 to 21 days.

Drug: Recombinant human hyaluronidase PH20; Drug: Insulin aspart; Drug: Insulin lispro

Interventions

Sham Injection DRUG

Insulin (Aspart or Lispro)-Sham

Recombinant human hyaluronidase PH20 DRUG

Also known as: rHuPH20, PH20, Hylenex

Insulin (Aspart or Lispro)-rHuPH20

Insulin aspart DRUG

Also known as: Novolog, Aspart

Insulin (Aspart or Lispro)-Sham; Insulin (Aspart or Lispro)-rHuPH20

Insulin lispro DRUG

Also known as: Humalog, Lispro

Insulin (Aspart or Lispro)-Sham; Insulin (Aspart or Lispro)-rHuPH20

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females of age 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 ≥12 months. Nonsmoking means abstinence from cigarettes and cigars for 3 months and negative cotinine screening tests at screening.
• Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m²), inclusive.
• Glycosylated hemoglobin A1c (HbA1c) ≤10% based on local laboratory results.
• Fasting connecting peptide of insulin (C-peptide) \<0.6 nanograms per milliliter (ng/mL).
• Current treatment with insulin \<90 units per day (U/d).
• Current use of rapid acting insulin analog.
• Routine use of CSII as the primary route of insulin administration for at least 3 months prior to screening
• Participants 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 the study protocol.

You may not qualify if:

• Known or suspected allergy to any component of any of the study drugs in this study.
• Previous enrollment in this study.
• Use of drugs that may interfere with the interpretation of study 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 (for example, coumadin or heparin) will be excluded.
• Use of any long-acting insulin injection within 72 hours of Study Day 1; participants will continue to refrain from use throughout the duration of the study (Phases I and II).
• 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 the Screening Visit(s) in this study.
• Pregnancy, breastfeeding, 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 Study Day 1.

Sponsors & Collaborators

• Halozyme Therapeutics: lead

Study Sites (1)

Profil Institute for Clinical Research

Chula Vista, California, 91911, United States

Location

Related Links

• Sponsor's Website

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

salicylhydroxamic acid; Insulin Aspart; Insulin Lispro

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Vice President, Endocrinology Clinical Development
• Organization: Halozyme Therapeutics, Inc

858-794-8889

Study Officials

• Linda Morrow, MD

  Profil Institute for Clinical Research, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2012
• First Posted: February 6, 2012
• Study Start: December 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: September 1, 2013
• Last Updated: February 26, 2019
• Results First Posted: September 29, 2014

Record last verified: 2019-02

Locations

US (1)