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

NCT00979875 | Completed Phase 1 Results

• 1 other identifier: HALO-117-104
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

insulin; recombinant human hyaluronidase; Healthy volunteers

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Time to Maximum Serum Insulin Concentration (Tmax)

  Predose up to 480 minutes postdose

• Time to Early and Late 50% Maximum Serum Insulin Concentration (t[50%Max])

  Predose up to 480 minutes postdose

• Time to Maximum Glucose Infusion Rate (tGIR[Max])

  Predose up to 480 minutes postdose

• Percentage of Total Area Under the Concentration-time Curve for Serum Insulin Attained by Time t (AUC0-t)

  Predose up to 120 minutes postdose

• Time to Percentage of Total Insulin Exposure

  Predose up to 480 minutes postdose

Study Arms (1)

Lispro+PH20, Lispro, Glulis+PH20, Glulis, Aspart+PH20, Aspart

EXPERIMENTAL

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); Drug: Insulin lispro; Drug: Insulin glulisine; Drug: Insulin aspart

Interventions

Recombinant human hyaluronidase PH20 (rHuPH20) DRUG

Also known as: HYLENEX, PH20

Lispro+PH20, Lispro, Glulis+PH20, Glulis, Aspart+PH20, Aspart

Insulin lispro DRUG

Also known as: Humalog, Lispro

Lispro+PH20, Lispro, Glulis+PH20, Glulis, Aspart+PH20, Aspart

Insulin glulisine DRUG

Also known as: Apidra, Glulisine

Lispro+PH20, Lispro, Glulis+PH20, Glulis, Aspart+PH20, Aspart

Insulin aspart DRUG

Also known as: NovoLog, Aspart

Lispro+PH20, Lispro, Glulis+PH20, Glulis, Aspart+PH20, Aspart

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Halozyme Therapeutics: lead

Study Sites (1)

Profil Institute for Clinical Research, Inc.

Chula Vista, California, 91911, United States

Location

Related Publications (1)

• 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.

  PMID: 23043164 DERIVED

MeSH Terms

Conditions

Insulin Resistance

Interventions

Insulin Lispro; insulin glulisine; Insulin Aspart

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic 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

• Marcus Hompesch, M.D.

  Profil Institute for Clinical Research, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2009
• First Posted: September 18, 2009
• Study Start: September 1, 2009
• Primary Completion: February 1, 2010
• Study Completion: May 1, 2010
• Last Updated: July 14, 2014
• Results First Posted: July 14, 2014

Record last verified: 2014-06

Locations

US (1)