A Pharmacokinetic and Glucodynamic Study of Subcutaneously Administered Insulin Analogs With rHuPH20 Compared to Insulin Analogs Alone

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT00979875
First received: September 17, 2009
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

This is a single-center, Phase 1, randomized, double-blind, 6-way crossover study to determine insulin pharmacokinetics, insulin glucodynamics, safety, and tolerability of subcutaneously administered dose(s) of insulin lispro + recombinant human hyaluronidase PH20 (rHuPH20), insulin lispro alone, insulin glulisine + rHuPH20, insulin glulisine alone, insulin aspart + rHuPH20, and insulin aspart alone.


Condition Intervention Phase
Healthy
Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Drug: Insulin lispro
Drug: Insulin glulisine
Drug: Insulin aspart
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Phase 1, Randomized, Double-Blind, Pharmacokinetic and Glucodynamic, 6-Way Crossover Study of Subcutaneously Administered Insulin Analogs With Recombinant Human Hyaluronidase (rHuPH20) Compared to Insulin Analogs Alone in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by Halozyme Therapeutics:

Primary Outcome Measures:
  • Area Under the Concentration-time Curve for Serum Insulin From Time 0 to 60 Minutes (AUC0-60) [ Time Frame: Predose up to 60 minutes postdose ] [ Designated as safety issue: No ]
    Area under the concentration (AUC)-time curve was derived as the area under the serum insulin concentration profile from 0 to 60 minutes. Blood samples were taken 30, 20, and 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); and at 20, 25, 30, 45, and 60 mins after each injection.


Secondary Outcome Measures:
  • Time to Maximum Serum Insulin Concentration (Tmax) [ Time Frame: Predose up to 480 minutes postdose ] [ Designated as safety issue: No ]
    Tmax was determined as the timepoint where the maximum of all valid concentration measurements for each measurement series was observed. Samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); every 30 mins (from 90 to 240 mins); and every 60 mins (from 240 to 480 mins) after each injection.

  • Time to Early and Late 50% Maximum Serum Insulin Concentration (t[50%Max]) [ Time Frame: Predose up to 480 minutes postdose ] [ Designated as safety issue: No ]
    Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); every 30 mins (from 90 to 240 mins); and every 60 mins (from 240 to 480 mins) after each injection.

  • Time to Maximum Glucose Infusion Rate (tGIR[Max]) [ Time Frame: Predose up to 480 minutes postdose ] [ Designated as safety issue: No ]
    Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); every 30 mins (from 90 to 240 mins); and every 60 mins (from 240 to 480 mins) after each injection.

  • Percentage of Total Area Under the Concentration-time Curve for Serum Insulin Attained by Time t (AUC0-t) [ Time Frame: Predose up to 120 minutes postdose ] [ Designated as safety issue: No ]
    Percentage of total area under the concentration (AUC)-time curve at 15, 30, 60, 120 minutes after injection was measured. Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); and at 90 and 120 mins after each injection.

  • Time to Percentage of Total Insulin Exposure [ Time Frame: Predose up to 480 minutes postdose ] [ Designated as safety issue: No ]
    Time to 10% and 50% of total insulin exposure was measured. Samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); every 30 mins (from 90 to 240 mins); and every 60 mins (from 240 to 480 mins) after each injection.


Enrollment: 14
Study Start Date: September 2009
Study Completion Date: May 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lispro+PH20, Lispro, Glulis+PH20, Glulis, Aspart+PH20, Aspart

All participants were randomized to 1 of 6 treatment sequences (ABC, ACB, BAC, BCA, CAB, or CBA), each of which was comprised of the same 3 interventions (A, B, and C). Each intervention was separated by a 3- to 14-day washout.

Intervention A: Participants received a single, subcutaneous (SC) injection of 95 units per milliliter (U/mL) Lispro + 5 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20 (PH20) and a single, SC injection of 95 U/mL Lispro alone 3 to 14 days apart.

Intervention B: Participants received a single, SC injection of 95 U/mL Glulisine (Glulis) + 5 µg/mL PH20 and a single, SC injection of 95 U/mL Glulis alone 3 to 14 days apart.

Intervention C: Participants received a single, SC injection of 95 U/mL Aspart + 5 µg/mL PH20 and a single, SC injection of 95 U/mL Aspart alone 3 to 14 days apart.

Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Other Names:
  • HYLENEX
  • PH20
Drug: Insulin lispro
Other Names:
  • Humalog
  • Lispro
Drug: Insulin glulisine
Other Names:
  • Apidra
  • Glulisine
Drug: Insulin aspart
Other Names:
  • NovoLog
  • Aspart

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy participants between the ages of 18 and 55 years, inclusive (healthy is defined as no clinically relevant abnormalities).
  • Body mass index (BMI) between 18-27 kilograms per meter squared (kg/m^2), inclusive.
  • Total body weight >65 kilograms (kg) (143 pounds [lb]) for men and >46 kg (101 lb) for women.
  • Decision making capacity and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including adequate venous access.
  • Vital signs (blood pressure [BP], pulse rate, body temperature) within normal range or, if out of range, assessed by the Principal Investigator as not clinically significant.
  • Fasting blood glucose level <100 milligrams per deciliter (mg/dL) at screening.
  • A negative serum pregnancy test (if female of childbearing potential).
  • Female participants of childbearing potential must agree to practice effective birth control or abstinence currently and agree to continue to do so for the duration of their time on study.
  • Signed, written institutional review board (IRB)-approved informed consent.

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, oncologic, or neurologic (to include history of seizures) disease; hypoglycemic episodes; intercurrent illness (such as influenza); or allergic disease (including severe drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Clinical significance to be determined by the Principal Investigator.
  • As judged by the investigator, clinically significant findings in routine laboratory data. (Anemia with hematocrit less than 33% at screening is specifically exclusionary.)
  • Known history of diabetes mellitus (type 1 or type 2) or gestational diabetes.
  • Known allergy to hyaluronidase or any other ingredient in the study drug.
  • Positive human immunodeficiency virus (HIV) 1, hepatitis B, or hepatitis C antibody test.
  • History or evidence of alcohol or drug abuse.
  • History or evidence of use of any tobacco- or nicotine-containing product within 6 months prior to screening and a screening qualitative urine nicotine test.
  • Use of drugs that may interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action or glucose utilization.
  • Blood donation or high volume phlebotomy, for example, >100 milliliters (mL), within 56 days before dosing.
  • Participation in a study of any investigational drug or device 30 days before enrollment in this study.
  • The participant is unfit for the study in the opinion of the investigator.
  • Women who are pregnant or breast-feeding.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00979875

Locations
United States, California
Profil Institute for Clinical Research, Inc.
Chula Vista, California, United States, 91911
Sponsors and Collaborators
Halozyme Therapeutics
Investigators
Principal Investigator: Marcus Hompesch, M.D. Profil Institute for Clinical Research, Inc.
  More Information

No publications provided by Halozyme Therapeutics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT00979875     History of Changes
Other Study ID Numbers: HALO-117-104
Study First Received: September 17, 2009
Results First Received: June 12, 2014
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Halozyme Therapeutics:
insulin
recombinant human hyaluronidase
Healthy volunteers

Additional relevant MeSH terms:
Insulin aspart
Insulin LISPRO
Insulin glulisine
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014