Safety/Efficacy Study of Subcutaneously Injected Prandial Insulins Compared to Insulin Lispro Alone in Patients With Type 2 Diabetes Mellitus

NCT01194258 | Completed Phase 2 Results

• 1 other identifier: HALO-117-206
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 22

Brief Summary

The purpose of the study was to compare Humalog (insulin lispro)-recombinant human hyaluronidase PH20 (rHuPH20) or Novolog (insulin aspart)-rHuPH20 to insulin lispro for the treatment of Type 2 diabetes mellitus (T2DM) in basal-bolus therapy.

Conditions

Diabetes Mellitus, Type II

Keywords

Type 2 diabetes

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Glycosylated Hemoglobin A1C (HbA1C) at the End of Each Treatment Period

  Change in glycosylated hemoglobin A1C (HbA1C) from baseline (Week 0) to end of treatment period (Week 12 and Week 24) is presented. Data are presented by combined treatment group (Lispro-recombinant human hyaluronidase PH20 (PH20) + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin lispro from both groups). Least squares (LS) means were calculated from linear contrasts of mixed effects linear models with treatment (Lispro, Aspart), PH20 (yes, no), and treatment sequence as fixed effects and participant within treatment sequence as a random effect.

  Baseline, Week 12 and Week 24

Secondary Outcomes (5)

• Mean Daily Insulin Dose as Recorded During 10-Point Glucose Monitoring

  Week 10 and Week 22

• Percentage of Participants Meeting Glucose Targets at Least 2/3 of the Time

  Baseline through Week 24, excluding 10-point glucose monitoring days

• Rates of Hypoglycemia at the End of Each Treatment Period

  Week 12 and Week 24

• Change From Baseline in Body Weight at the End of Each Treatment Period

  Baseline, Week 12 and Week 24

• Mean Daily PPG Excursions

  Week 10 and Week 22

Study Arms (2)

Lispro-PH20/Insulin lispro

EXPERIMENTAL

All enrolled participants underwent a titration period of 4 to 6 weeks in which they received 100 units per milliliter (U/mL) insulin glulisine, 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. Lispro-PH20 (Treatment A): 100 U/mL insulin lispro with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (combined: Lispro-PH20), injected SC, pre-meals, with doses titrated to each participant individually. Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually. Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Drug: Insulin lispro; Drug: Recombinant human hyaluronidase PH20; Drug: Insulin glulisine; Drug: Insulin glargine

Aspart-PH20/Insulin Lispro

EXPERIMENTAL

All enrolled participants underwent a titration period of 4 to 6 weeks in which they received 100 U/mL insulin glulisine, injected 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. Aspart-PH20 (Treatment A): 100 U/mL insulin aspart with 5.0 µg/mL rHuPH20 (combined: Aspart-PH20), injected SC, pre-meals, with doses titrated to each participant individually. Insulin lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually. Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

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

Interventions

Insulin lispro DRUG

Also known as: Lispro, Humalog

Aspart-PH20/Insulin Lispro; Lispro-PH20/Insulin lispro

Insulin aspart DRUG

Also known as: Aspart, Novolog

Aspart-PH20/Insulin Lispro

Recombinant human hyaluronidase PH20 DRUG

Also known as: rHuPH20, PH20, Hylenex

Aspart-PH20/Insulin Lispro; Lispro-PH20/Insulin lispro

Insulin glulisine DRUG

Also known as: Apidra

Aspart-PH20/Insulin Lispro; Lispro-PH20/Insulin lispro

Insulin glargine DRUG

Also known as: Lantus

Aspart-PH20/Insulin Lispro; Lispro-PH20/Insulin lispro

Eligibility Criteria

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

You may qualify if:

• Males or females ≥18 years
• Type 2 diabetes mellitus (T2DM) treated with insulin ≥12 months and prandial insulin (at least 2 meals per day) for ≥2 months
• Body mass index (BMI) of 23.0 to 45.0 kilograms per meter squared (kg/m\^2)
• Glycosylated hemoglobin (HbA1C) level 7.0 to 8.5%, inclusive
• Fasting C-peptide \<0.6 nanograms per milliliter (ng/mL)
• Willingness to use insulin glargine twice a day as basal insulin for the duration of the study
• Willingness to avoid use of an insulin infusion pump or unblinded continuous glucose monitoring (CGM) during the study

You may not qualify if:

• Known or suspected allergy to any component of any of the study drugs
• Exclusive use of pre-mixed insulins
• Use of pramlintide, exenatide, and/or liraglutide within 30 days of screening
• Use of sulfonylureas within two months of screening
• Use of drugs (such as corticosteroids or antimetabolites) that could interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia, during the study or within 30 days of screening
• Recurrent severe hypoglycemia (more than 2 episodes over the last 6 months) or hypoglycemic unawareness, as judged by the investigator

Sponsors & Collaborators

• Halozyme Therapeutics: lead

Study Sites (22)

John Muir Physician Network Clinical Research Center

Concord, California, 94520, United States

Location

Medical Group of Encino

Encino, California, 91436, United States

Location

AMCR Institute, Inc.

Escondido, California, 92026, United States

Location

Marin Endocrine Care and Research

Greenbrae, California, 94904, United States

Location

Mills-Peninsula Health Services

San Mateo, California, 94401, United States

Location

Center for Diabetes and Endocrine Care

Hollywood, Florida, 33021, United States

Location

Diabetes Research Institute

Miami, Florida, 33136, United States

Location

Baptist Diabetes Associates

Miami, Florida, 33156, United States

Location

Rocky Mountain Diabetes and Osteoporosis Center

Idaho Falls, Idaho, 83404, United States

Location

Mid-America Diabetes Associates

Wichita, Kansas, 67211, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Medstar Research Institute

Hyattsville, Maryland, 20782, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

International Diabetes Center

Minneapolis, Minnesota, 55416, United States

Location

Mercury Street Medical

Butte, Montana, 59701, United States

Location

Desert Endocrinology

Henderson, Nevada, 89052, United States

Location

Diabetes and Endocrinology Associates, PC

Rudd, North Carolina, 28557, United States

Location

UT Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

Texas Diabetes and Endocrinology

Round Rock, Texas, 78681, United States

Location

Cetero Research-San Antonio

San Antonio, Texas, 78229, United States

Location

West Olympia Internal Medicine

Olympia, Washington, 98502, United States

Location

University of Washington School of Medicine

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Insulin Lispro; Insulin Aspart; insulin glulisine; Insulin Glargine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine 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; Insulin, Long-Acting

Results Point of Contact

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

858-794-8889

Study Officials

• Douglas Muchmore, M.D.

  Halozyme Therapeutics

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2010
• First Posted: September 2, 2010
• Study Start: August 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: August 20, 2014
• Results First Posted: August 20, 2014

Record last verified: 2014-08

Locations

US (22)