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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Insulin lispro; Drug: Insulin aspart; Drug: Insulin glulisine; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Profil Institute for Clinical Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve for Serum Insulin From Time 0 to 60 Minutes (AUC0-60)	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.	Predose up to 60 minutes postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Maximum Serum Insulin Concentration (Tmax)	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.	Predose up to 480 minutes postdose
Time to Early and Late 50% Maximum Serum Insulin Concentration (t[50%Max])	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.	Predose up to 480 minutes postdose
Time to Maximum Glucose Infusion Rate (tGIR[Max])	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.	Predose up to 480 minutes postdose
Percentage of Total Area Under the Concentration-time Curve for Serum Insulin Attained by Time t (AUC0-t)	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.	Predose up to 120 minutes postdose
Time to Percentage of Total Insulin Exposure	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.	Predose up to 480 minutes postdose

Collaborators and Investigators

• Sponsor: Halozyme Therapeutics
• Investigators: Principal Investigator: Marcus Hompesch, M.D., Profil Institute for Clinical Research, Inc.

Publications and helpful links

General Publications

• Morrow L, Muchmore DB, Hompesch M, Ludington EA, Vaughn DE. Comparative pharmacokinetics and insulin action for three rapid-acting insulin analogs injected subcutaneously with and without hyaluronidase. Diabetes Care. 2013 Feb;36(2):273-5. doi: 10.2337/dc12-0808. Epub 2012 Oct 5.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): February 1, 2010
• Study Completion (ACTUAL): May 1, 2010

Study Registration Dates

• First Submitted: September 17, 2009
• First Submitted That Met QC Criteria: September 17, 2009
• First Posted (ESTIMATE): September 18, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): July 14, 2014
• Last Update Submitted That Met QC Criteria: June 12, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Healthy volunteers; insulin; recombinant human hyaluronidase
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin Lispro; Insulin glulisine
• Other Study ID Numbers: HALO-117-104