Pharmacokinetic and Glucodynamic Crossover Study of Subcutaneously (SC) Administered Insulin Lispro + Recombinant Human Hyaluronidase (rHuPH20) and Regular Human Insulin + rHuPH20 Compared to Insulin Lispro Alone

NCT00862849 | Completed Phase 1 Results

• 1 other identifier: HALO-117-103
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Insulin lispro and regular human insulin are Food and Drug Administration (FDA)-approved medications 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 will be co-administered with both insulin lispro and regular human insulin in order to determine if it improves the absorption of these insulins to more closely mimic the body's natural increase in insulin in response to a meal.

Conditions

Diabetes Mellitus

Keywords

rHuPH20; Recombinant Human Hyaluronidase; Insulin Lispro; Regular Human Insulin

Outcome Measures

Primary Outcomes (1)

• Intra-participant Variability in Percent of Total Area Under the Plasma Insulin Concentration-Versus-Time Curve Attained by Time T (%AUC[0-T])

  Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); and every 5 mins (from 15 to 30 mins) after each injection. The percent coefficient of variation (CV%) was calculated as 100\*(standard deviation/mean). The intra-participant CV% was calculated directly from the 2 replications of each treatment. The CV% for percentage of total AUC is reported from 0 to 30 minutes.

  predose up to 30 minutes postdose

Secondary Outcomes (5)

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

  predose up to 480 minutes postdose

• Peak Serum Insulin Concentration (Cmax)

  predose up to 480 minutes postdose

• Time to Percentage of Total Glucose Infused

  predose up to 480 minutes postdose

• Percentage of Total Glucose Infused

  predose up to 240 minutes postdose

• Number of Treatment Emergent Adverse Events (TEAEs) Related to Study Drug

  first dose through 7 to 10 days after last dose

Study Arms (1)

Insulin Lispro, Regular Human Insulin, rHuPH20

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). Intervention A: a single, subcutaneous (SC) injection of 0.15 units per kilogram (U/kg) insulin lispro with 3.75 nanograms per kilogram (ng/kg) recombinant human hyaluronidase (rHuPH20) Intervention B: a single, SC injection of 0.15 U/kg regular human insulin (RHI) with 3.75 ng/kg rHuPH20 Intervention C: a single, SC injection of 0.15 U/kg insulin lispro alone There was a washout period of 3 to 14 days between interventions. The treatment sequence (ABC, ACB, BAC, BCA, CAB, or CBA) was repeated once so that each participant received up to 6 injections.

Drug: Insulin Lispro; Drug: Regular Human Insulin; Drug: rHuPH20

Interventions

Insulin Lispro DRUG

Also known as: Humalog

Insulin Lispro, Regular Human Insulin, rHuPH20

Regular Human Insulin DRUG

Also known as: RHI, Humulin R

Insulin Lispro, Regular Human Insulin, rHuPH20

rHuPH20 DRUG

Also known as: recombinant human hyaluronidase, HYLENEX

Insulin Lispro, Regular Human Insulin, rHuPH20

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, pulse rate, body temperature) within normal range or, if out of range, assessed by the Principal Investigator (PI) as not clinically significant (NCS).
• 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 be practicing 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 PI.
• 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) antibody test, hepatitis B (anti-hepatitis B surface antigen \[anti-HBsAg\]) or hepatitis C (anti-hepatitis C virus \[anti-HCV\]) 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 of screening and a screening qualitative urine nicotine test.
• Use of drugs that may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action or glucose utilization.
• Donation of blood in excess of 500 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, Ludington EA, Vaughn DE, Hompesch M. Reduction in intrasubject variability in the pharmacokinetic response to insulin after subcutaneous co-administration with recombinant human hyaluronidase in healthy volunteers. Diabetes Technol Ther. 2011 Oct;13(10):1039-45. doi: 10.1089/dia.2011.0115. Epub 2011 Jun 29.

  PMID: 21714645 RESULT

MeSH Terms

Conditions

Diabetes Mellitus; Insulin Resistance

Interventions

Insulin Lispro; Insulin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Proinsulin

Results Point of Contact

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

858-794-8889

Study Officials

• Linda A Morrow, M.D.

  Profil Institute for Clinical Research, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: March 13, 2009
• First Posted: March 17, 2009
• Study Start: March 1, 2009
• Primary Completion: June 1, 2009
• Study Completion: August 1, 2009
• Last Updated: July 22, 2014
• Results First Posted: July 11, 2014

Record last verified: 2014-07

Locations

US (1)