Safety Study of Subcutaneously-Injected Prandial INSULIN-PH20 NP Compared to Insulin Lispro Injection in Participants With Type 1 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00883558
Recruitment Status : Completed
First Posted : April 17, 2009
Results First Posted : September 8, 2014
Last Update Posted : September 8, 2014
Information provided by (Responsible Party):
Halozyme Therapeutics

Brief Summary:
Insulin lispro is approved by the Food and Drug Administration (FDA) for the treatment of diabetes mellitus. Recombinant human hyaluronidase (rHuPH20) is approved by the FDA as an aid to the absorption and dispersion of other injectable drugs. In this study, rHuPH20 combined with a non-preserved (NP) formulation of regular human insulin (INSULIN-PH20 NP) will be compared to insulin lispro with respect to absorption and action of insulin.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Insulin Lispro Drug: regular human insulin Drug: recombinant human hyaluronidase PH20 Drug: Insulin glargine Phase 2

Detailed Description:
The purpose of this study is to compare the safety and tolerability of INSULIN-PH20 NP versus insulin lispro alone.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Official Title: A Phase II, Randomized, Open Label, 2-Way Crossover, Safety Study of Subcutaneously Injected Prandial INSULIN-PH20 NP Compared to Insulin Analog Injection in Patients With Type 1 Diabetes
Study Start Date : May 2009
Actual Primary Completion Date : February 2010
Actual Study Completion Date : April 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: INSULIN-PH20 NP / Insulin Lispro

All enrolled participants underwent a 1-month dose titration period and received 100 units per milliliter (U/mL) insulin lispro, 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.

INSULIN-PH20 NP (Treatment A): 100 U/mL non-preserved (NP) formulation of regular human insulin with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, doses titrated to each participant individually.

Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, doses titrated to each participant individually.

Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine or maintained their usual regimen through an insulin pump.

Drug: Insulin Lispro
Other Name: Humalog

Drug: regular human insulin
Other Name: Humulin R

Drug: recombinant human hyaluronidase PH20
Other Names:
  • Hylenex
  • rHuPH20
  • PH20

Drug: Insulin glargine
Other Name: Lantus

Primary Outcome Measures :
  1. Postprandial Glucose Excursion [ Time Frame: Week 14 and Week 26 ]
    A 2-hour postprandial glucose excursion was measured for 3 meals over 3 days during each treatment cycle (3 days during Week 14 of the first treatment cycle and 3 days during Week 26 of the second treatment cycle). For each of the 3 days, the mealtime (breakfast, lunch, and dinner) excursions were calculated as the post-meal glucose value minus the pre-meal value as determined by 8-point glucose monitoring. The average of all excursions over the 3 days for the corresponding treatment cycle is presented.

Secondary Outcome Measures :
  1. Time Spent With Blood Glucose Value Outside a 71-139 Milligrams Per Deciliter (mg/dL) Range During Continuous Glucose Monitoring [ Time Frame: Week 14 and Week 26 ]
    Participants were provided a continuous glucose monitoring (CGM) device, consisting of a sensor, transmitter, and receiver. Total time the participant's blood glucose was outside the 71-139 mg/dL range during 3 days of CGM during each treatment cycle (3 days during Week 14 of the first treatment cycle and 3 days during Week 26 of the second treatment cycle) is presented.

  2. Number of Participants With Hypoglycemic Events [ Time Frame: Baseline through Week 29 ]
    The number of participants with at least one hypoglycemic event (HE) reported during the entire study is presented. Additionally, the number of participants with severe HEs (those that necessitated administration of carbohydrate or glucagon, or resuscitation, by another person) is also presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male or female 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.
  • Participants with Type 1 diabetes mellitus (T1DM) (per World Health Organization [WHO] criteria) treated with insulin for ≥24 months.
  • Participants who use an insulin infusion pump for basal insulin administration must be on the device for at least 90 days prior to screening.
  • Body mass index (BMI) 18.0 to 35.0 kilograms per square meter (kg/m^2), inclusive.
  • Glycosylated hemoglobin A1c (HbA1c) ≤7.5 % based on central laboratory screening results.
  • Fasting C-peptide <0.6 nanograms per milliliter (ng/mL).
  • Participants should be in good general health based on medical history and physical examination and without medical conditions that might prevent the completion of study drug injections and assessments required in this protocol.

Exclusion Criteria:

  • Known or suspected allergy to any component of any of the study drugs in this study.
  • Previous enrollment in this study. Participants who fail Screening may attempt to rescreen into the study.
  • A participant who has proliferative retinopathy or maculopathy, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
  • As judged by the Investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on electrocardiogram [ECG]), hepatic, neurological, renal, genitourinary, or hematological systems.
  • 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). Three attempts may be performed to measure blood pressure.
  • History of any illness or disease that in the opinion of the Investigator might confound the results of the study or pose additional risk in administering the study drugs to the participant.
  • As judged by the Investigator, clinically significant findings in routine laboratory data.
  • Use of drugs (such as systemic corticosteroids) 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.
  • Recurrent severe hypoglycemia (more than 2 episodes over the last 6 months) or hypoglycemic unawareness, as judged by the Investigator.
  • Current addiction to alcohol or substances of abuse, as determined by the Investigator.
  • 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).
  • Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study.
  • Receipt of any investigational drug within 4 weeks of Screening.
  • Any condition (intrinsic or extrinsic) that in the judgment of the Investigator will interfere with study participation or evaluation of data. Examples would include: renal insufficiency (serum creatinine >1.5 milligrams per deciliter [mg/dL] for males or >1.4 mg/dL for females), congestive heart failure required medication treatment, and cardiac disease with New York Heart Association (NYHA) Functional Capacity of III/IV.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00883558

United States, Colorado
Barbara Davis Center for Childhood Diabetes
Aurora, Colorado, United States, 80045
United States, Florida
Diabetes Research Institute
Miami, Florida, United States, 33136
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Montana
Mercury Street Medical
Butte, Montana, United States, 59701
United States, North Carolina
UNC Diabetes Care Center/Highgate Specialty Center
Durham, North Carolina, United States, 27713
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Texas
Texas Diabetes and Endocrinology
Austin, Texas, United States, 78731
United States, Washington
West Olympia Internal Medicine
Olympia, Washington, United States, 98502
Sponsors and Collaborators
Halozyme Therapeutics
Study Director: Douglas Muchmore, M.D. Halozyme Therapeutics

Responsible Party: Halozyme Therapeutics Identifier: NCT00883558     History of Changes
Other Study ID Numbers: HALO-117-203
First Posted: April 17, 2009    Key Record Dates
Results First Posted: September 8, 2014
Last Update Posted: September 8, 2014
Last Verified: August 2014

Keywords provided by Halozyme Therapeutics:
recombinant human hyaluronidase (rHuPH20)
Insulin lispro
regular human insulin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin Glargine
Insulin Lispro
Hypoglycemic Agents
Physiological Effects of Drugs