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

NCT ID: NCT00979875

Last Updated: 2014-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2010-05-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: DOUBLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type: DRUG

Insulin lispro

Intervention Type: DRUG

Insulin glulisine

Intervention Type: DRUG

Insulin aspart

Intervention Type: DRUG

Interventions

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type: DRUG

Insulin lispro

Intervention Type: DRUG

Insulin glulisine

Intervention Type: DRUG

Insulin aspart

Intervention Type: DRUG

Other Intervention Names

HYLENEX; PH20; Humalog; Lispro; Apidra; Glulisine; NovoLog; Aspart

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• As judged by the investigator, clinically significant findings in routine laboratory data. (Anemia with hematocrit less than 33% at screening is specifically exclusionary.)
• 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.

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

Sponsors

Halozyme Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marcus Hompesch, M.D.

Role: PRINCIPAL_INVESTIGATOR

Profil Institute for Clinical Research, Inc.

Locations

Profil Institute for Clinical Research, Inc.

Chula Vista, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 23043164 (View on PubMed)

Other Identifiers

HALO-117-104

Identifier Type: -

Identifier Source: org_study_id