Pharmacokinetic (PK),, Pharmacodynamic (PD) of Subcutaneously Administered Humalog® With and Without Recombinant Human Hyaluronidase (rHuPH20)and Humulin R® With and Without rHuPH20 - Full Text View

Sponsored by:	Halozyme Therapeutics
Information provided by:	Halozyme Therapeutics
ClinicalTrials.gov Identifier:	NCT00705536

Purpose

The purpose of the study was to compare the pharmacokinetics and pharmacodynamics of Humalog or Humulin R insulin when administered as a single 20-U subcutaneous (SC) injection with or without coadministration of rHuPH20.

The study hypothesizes that the time required to reach maximum insulin concentration (Tmax) when insulin is administered with rHuPH20 will be comparable or shorter than the time required without rHuPH20.

Condition	Intervention	Phase
Insulin Diabetes Volunteers	Drug: Humalog Drug: Humulin R	Phase I

Drug Information available for: Insulin Hyaluronidase Insulin lispro

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Health Services Research, Randomized, Double Blind (Subject, Investigator), Crossover Assignment, Safety/Efficacy Study
Official Title:	A Phase I, Randomized, Double-Blind Crossover Pharmacokinetic, Pharmacodynamic and Safety Study of Subcutaneously Administered Humalog® (Insulin Lispro Injection; Fast-Acting Insulin) With and Without Recombinant Human Hyaluronidase (rHuPH20) Versus Subcutaneously Administered Humulin R® (Regular Insulin Injection) With and Without rHuPH20

Further study details as provided by Halozyme Therapeutics:

Primary Outcome Measures:

Compare PK of a single SC injection of Humalog or Humulin R insulin with or without rHuPH20, by determining Tmax, Cmax, AUC0→Tmaxw/PH20, AUC0→t', and relative bioavailability of serum insulin concentrations collected at specified time points. [ Time Frame: 3 mL blood draws were taken 10 and 1 minute (min) prior to treatment, every 3 min for the first 60 minutes of each treatment, every 15 min from 60 min to 3 hr and every hr. from 3 to 6 hrs. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Compare PD of a single SC injection of Humalog or Humulin R insulin with rHuPH20 to a SC injection of Humalog or Humulin without rHuPH20, by comparing Tmax, Tearly 50%, Tlate 50%, and AUC0→t' of glucose infusion rate (GIR). [ Time Frame: 3 mL blood draws were taken 10 and 1 minute (min) prior to treatment, every 3 min for the first 60 minutes of each treatment, every 15 min from 60 min to 3 hr and every hr. from 3 to 6 hrs. ] [ Designated as safety issue: Yes ]

Enrollment:	26
Study Start Date:	January 2008
Study Completion Date:	March 2008
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Stage 1: Active Comparator Subjects randomized to Humalog with or without rHuPH20	Drug: Humalog 20 U of Humalog with or without 300 U of rHupH20
Stage 2: Active Comparator Subjects randomized to Humulin R with or without rHuPH20	Drug: Humulin R 20 U of Humulin R with or without 240 U rHuPH20

Eligibility

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

Criteria

Inclusion Criteria:

Healthy male subjects between the ages of 18 and 55 years, inclusive.
BMI between 18-28 kg/m2, inclusive and a total body weight >70 kg (154 lb).
Subject willing and able to comply with protocol.
Vital signs within normal range.
Within 7 days before the first injection: metabolic panel and complete blood count (CBC) within the laboratory normal reference range.
Fasting plasma glucose level within the normal range 90 to 110 mg/dL inclusive the morning of the glucose clamp.
Subjects while taking part in this study should agree not to father a child or donate sperm and agree to use an effective method of contraception during the study and for at least 30 days after study completion.
Willingness and ability to sign an informed consent form (ICF).

Exclusion Criteria:

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic (to include history of seizures), history of hypoglycemic episodes or allergic disease.
Known history of diabetes mellitus.
Prior exposure to any insulin or insulin analogs.
Known allergy to hyaluronidase or any other ingredient in HYLENEX.
Known allergy to bee or vespid venom.
Positive urine drug screen.
Positive HIV 1 and HIV 2 (human immunodeficiency virus) antibody test, hepatitis B (anti-HBsA) or hepatitis C (anti-HCV) antibody test.
Any 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 or screening quantitative urine nicotine concentration >50 ng/mL.
Use of prescription or nonprescription drugs within 7 days or 5 half-lives, whichever is shorter. Excluded from this list is acetaminophen at doses of less than or equal to 1 g/day.
Donation of blood in excess of 500 mL within 56 days before dosing.
Failure to limit alcohol consumption and refrain from exercise within 48 hours before each injection.
Known clinically significant intercurrent illness or other major systemic disease that would unduly risk the subject's safety or interfere with the interpretation of results.
Participation in a study of any investigational drug or device 30 days before enrollment in this study.
In the opinion of the investigator that the subject is unfit for the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00705536

Locations

United States, Texas
DGD Research, Inc.
San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Halozyme Therapeutics

Investigators

Principal Investigator:

Mark S. Kipnes, MD

Diabetes and Glandular Disease Research Associates Inc.

More Information

Responsible Party:	Halozyme Therapeutics ( Richard Yocum, M.D., Vice President of Clinical Dev and Med Affairs )
Study ID Numbers:	HZ2-07-04
Study First Received:	June 24, 2008
Last Updated:	June 25, 2008
ClinicalTrials.gov Identifier:	NCT00705536
Health Authority:	United States: Food and Drug Administration

Keywords provided by Halozyme Therapeutics:

rHuPH20
Hyaluronidase
Insulin

Study placed in the following topic categories:

Diabetes Mellitus
Insulin LISPRO
Insulin

Additional relevant MeSH terms:

Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009