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

NCT ID: NCT00705536

Last Updated: 2019-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2008-02-29

Brief Summary

The purpose of the study is to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of Humalog (insulin lispro) or Humulin-R (recombinant human insulin) when administered as a single subcutaneous (SC) injection of 20 units (U) with or without coadministration of recombinant human hyaluronidase PH20 (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.

Conditions

Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: DOUBLE

Study Groups

Humalog first, then Humalog + rHuPH20

Humalog first, then Humalog + recombinant human hyaluronidase PH20 (rHuPH20)

A single subcutaneous (SC) injection of 20 units (U) Humalog on Day 1 of the study, followed by a single SC injection of 20 U Humalog + 300 U rHuPH20 after a washout period of at least 6 days

Group Type: ACTIVE_COMPARATOR

Humalog

Intervention Type: DRUG

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type: DRUG

Humalog + rHuPH20 first, then Humalog

Humalog + recombinant human hyaluronidase PH20 (rHuPH20) first, then Humalog

A single subcutaneous (SC) injection of 20 units (U) Humalog + 300 U rHuPH20 on Day 1 of the study, followed by a single SC injection of 20 U Humalog after a washout period of at least 6 days

Group Type: ACTIVE_COMPARATOR

Humalog

Intervention Type: DRUG

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type: DRUG

Humulin-R first, then Humulin-R + rHuPH20

Humulin-R (recombinant human insulin) first, then Humulin-R + recombinant human hyaluronidase PH20 (rHuPH20)

A single subcutaneous (SC) injection of 20 units (U) Humulin-R on Day 1 of the study, followed by a single SC injection of 20 U Humulin-R + 240 U rHuPH20 after a washout period of at least 6 days

Group Type: ACTIVE_COMPARATOR

Humulin-R

Intervention Type: DRUG

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type: DRUG

Humulin-R + rHuPH20 first, then Humulin-R

Humulin-R (recombinant human insulin) + recombinant human hyaluronidase PH20 (rHuPH20) first, then Humulin-R

A single subcutaneous (SC) injection of 20 units (U) Humulin-R + 240 U rHuPH20 on Day 1 of the study, followed by a single SC injection of 20 U Humulin-R after a washout period of at least 6 days

Group Type: ACTIVE_COMPARATOR

Humulin-R

Intervention Type: DRUG

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type: DRUG

Interventions

Humalog

Intervention Type: DRUG

Humulin-R

Intervention Type: DRUG

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type: DRUG

Other Intervention Names

Insulin lispro; Humulin; Recombinant human insulin; PH20; HYLENEX

Eligibility Criteria

Inclusion Criteria

1. Healthy male participants aged 18 to 55 years.

2. Body mass index (BMI) 18 to 28 kilograms per meter squared (kg/m^2) and total body weight >70 kilograms (kg) (154 pounds [lb]).

3. Willingness and ability to comply with the protocol.

4. Vital signs within the normal range.

5. Within 7 days before the first injection, metabolic panel results and complete blood count (CBC) within the laboratory normal reference range.

6. Fasting plasma glucose within the normal range of 90 to 110 milligrams per deciliter (mg/dL) on the morning of the glucose clamp.

7. Agreement not to father a child or donate sperm and to use effective contraception during the study and for at least 30 days after study completion.

8. Willingness and ability to sign an informed consent form.

Exclusion Criteria

1. Evidence or history of clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic (to include history of seizures) or allergic disease, or history of hypoglycemic episodes.

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 results.

7. Positive human immunodeficiency virus (HIV) 1, HIV 2, hepatitis B, or hepatitis C antibody test result.

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 urine nicotine concentration >50 nanograms per milliliter (ng/mL).

10. Use of prescription or nonprescription drugs within 7 days or 5 half-lives, whichever was shorter, except acetaminophen at doses of less than or equal to 1 gram per day (g/day).

11. Donation of blood in excess of 500 milliliters (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 participant'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. Unfitness for the study, in the investigator's opinion.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Halozyme Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark S. Kipnes, MD

Role: PRINCIPAL_INVESTIGATOR

Diabetes and Glandular Disease Research Associates Inc.

Locations

Diabetes and Glandular Disease Research, Inc.

San Antonio, Texas, United States

Countries

United States

References

Vaughn DE, Yocum RC, Muchmore DB, Sugarman BJ, Vick AM, Bilinsky IP, Frost GI. Accelerated pharmacokinetics and glucodynamics of prandial insulins injected with recombinant human hyaluronidase. Diabetes Technol Ther. 2009 Jun;11(6):345-52. doi: 10.1089/dia.2009.0013.

Reference Type: RESULT

PMID: 19459762 (View on PubMed)

Other Identifiers

HZ2-07-04

Identifier Type: -

Identifier Source: org_study_id