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”

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.

Study Type: Interventional

Study Design: Health Services Research, Randomized, Double Blind (Subject, Investigator), Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: February 2008

Intervention(s) in this Clinical Trial

• Drug: Humalog
  • 20 U of Humalog with or without 300 U of rHupH20
• Drug: Humulin R
  • 20 U of Humulin R with or without 240 U rHuPH20

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Stage 1
  • Subjects randomized to Humalog with or without rHuPH20
• Active Comparator: Stage 2
  • Subjects randomized to Humulin R with or without rHuPH20

Primary 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.
    Safety Issue?: Yes

Secondary 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.
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Healthy male subjects between the ages of 18 and 55 years, inclusive.
• 2. BMI between 18-28 kg/m2, inclusive and a total body weight >70 kg (154 lb).
• 3. Subject willing and able to comply with protocol.
• 4. Vital signs within normal range.
• 5. Within 7 days before the first injection: metabolic panel and complete blood count (CBC) within the laboratory normal reference range.
• 6. Fasting plasma glucose level within the normal range 90 to 110 mg/dL inclusive the morning of the glucose clamp.
• 7. 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.
• 8. Willingness and ability to sign an informed consent form (ICF).

Exclusion Criteria:

• 1. 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.
• 2. Known history of diabetes mellitus.
• 3. Prior exposure to any insulin or insulin analogs.
• 4. Known allergy to hyaluronidase or any other ingredient in HYLENEX.
• 5. Known allergy to bee or vespid venom.
• 6. Positive urine drug screen.
• 7. Positive HIV 1 and HIV 2 (human immunodeficiency virus) antibody test, hepatitis B (anti-HBsA) or hepatitis C (anti-HCV) antibody test.
• 8. Any history or evidence of alcohol or drug abuse.
• 9. 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.
• 10. 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.
• 11. Donation of blood in excess of 500 mL within 56 days before dosing.
• 12. Failure to limit alcohol consumption and refrain from exercise within 48 hours before each injection.
• 13. 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.
• 14. Participation in a study of any investigational drug or device 30 days before enrollment in this study.
• 15. In the opinion of the investigator that the subject is unfit for the study.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Halozyme Therapeutics

Overall Clinical Trial Officials and Contacts

Mark S. Kipnes, MD Principal Investigator Diabetes and Glandular Disease Research Associates Inc.  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00705536

Study ID Number: HZ2-07-04

ClinicalTrials.gov Identifier: NCT00705536

Health Authority: United States: Food and Drug Administration