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

Halozyme

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Insulin glulisine; Drug: Insulin aspart; Drug: Insulin lispro; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00979875

HALO-117-104

Details and patient eligibility

About

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.

Enrollment: 14 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

14 participants in 1 patient group

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

Experimental group

Description:

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.

Treatment:

Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

Drug: Insulin lispro

Drug: Insulin aspart

Drug: Insulin glulisine