Dose-Ranging, Pharmacokinetic (PK), Glucodynamic (GD), Safety and Tolerability Study of Subcutaneously (SC) Administered Humulin R and Humalog With or Without rHuPH20

NCT00803972 | Completed Phase 1

• 1 other identifier: HZ2-08-04
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, Phase I, open-label, single-blind (subjects blinded to the contents of each injection), 4 stage study designed to determine the PK, GD, safety, tolerability, and optimal ratio of rHuPH20 administered with fixed Humulin R or Humalog doses in healthy subjects.

Conditions

Healthy Volunteers

Keywords

Humalog; Humulin R; rHuPH20; Hylenex

Outcome Measures

Primary Outcomes (1)

• Insulin AUC

  0 to 60 minutes

Secondary Outcomes (1)

• Other insulin PK, GD and safety outcomes

  Day of each injection and 7 days after final dose

Study Arms (8)

Stage 1: 3 U insulin plus rHuPH20

EXPERIMENTAL

Participants will receive 3 Units (U) of regular insulin (100 U/milliliter \[mL\]), coadministered with sequential concentrations of 0, 1.25, 5, 10, 20, and 80 micrograms (μg)/mL recombinant human hyaluronidase (rHuPH20).

Drug: rHuPH20; Drug: Insulin Human Injection

Stage 1: 12 U insulin plus rHuPH20

EXPERIMENTAL

Participants will receive 12 U of regular insulin (100 U/mL), coadministered with sequential concentrations of 0, 1.25, 5, 10, 20, and 80 μg/mL rHuPH20.

Drug: rHuPH20; Drug: Insulin Human Injection

Stage 2: insulin plus rHuPH20

EXPERIMENTAL

Participants will receive 6, 12, and 24 U regular insulin (100 U/mL) in a randomly assigned order, with each insulin dose administered once with and once without 5 μg/mL rHuPH20.

Drug: rHuPH20; Drug: Insulin Human Injection

Stage 3: 1.5 U insulin lispro plus rHuPH20

EXPERIMENTAL

Participants will receive 1.5 U of insulin lispro (50 U/mL), coadministered with sequential concentrations of 0, 0.0625, 0.3125, 1.25, 5, and 20 μg/mL rHuPH20.

Drug: rHuPH20; Drug: Insulin Lispro Injection

Stage 3: 6 U insulin lispro plus rHuPH20

EXPERIMENTAL

Participants will receive 6 U of insulin lispro (50 U/mL), coadministered with sequential concentrations of 0, 0.0625, 0.3125, 1.25, 5, and 20 μg/mL rHuPH20.

Drug: rHuPH20; Drug: Insulin Lispro Injection

Stage 4: 95 U/mL insulin lispro plus 5 μg/mL rHuPH20

EXPERIMENTAL

Participants will receive 95 U/mL insulin lispro, administered once with and once without 5 μg/mL rHuPH20. At each insulin lispro concentration, participants will receive 2, 6, and 20 U lispro.

Drug: rHuPH20; Drug: Insulin Lispro Injection

Stage 4: 50 U/mL insulin lispro plus 5 μg/mL rHuPH20

EXPERIMENTAL

Participants will receive 50 U/mL insulin lispro, administered once with and once without 5 μg/mL rHuPH20. At each insulin lispro concentration, participants will receive 2, 6, and 20 U lispro.

Drug: rHuPH20; Drug: Insulin Lispro Injection

Stage 4: 25 U/mL insulin lispro plus 5 μg/mL rHuPH20

EXPERIMENTAL

Participants will receive 25 U/mL insulin lispro, administered once with and once without 5 μg/mL rHuPH20. At each insulin lispro concentration, participants will receive 2, 6, and 20 U lispro.

Drug: rHuPH20; Drug: Insulin Lispro Injection

Interventions

rHuPH20 DRUG

recombinant human hyaluronidase PH20

Stage 1: 12 U insulin plus rHuPH20; Stage 1: 3 U insulin plus rHuPH20; Stage 2: insulin plus rHuPH20; Stage 3: 1.5 U insulin lispro plus rHuPH20; Stage 3: 6 U insulin lispro plus rHuPH20; Stage 4: 25 U/mL insulin lispro plus 5 μg/mL rHuPH20; Stage 4: 50 U/mL insulin lispro plus 5 μg/mL rHuPH20; Stage 4: 95 U/mL insulin lispro plus 5 μg/mL rHuPH20

Insulin Human Injection DRUG

injection

Also known as: Humulin® R

Stage 1: 12 U insulin plus rHuPH20; Stage 1: 3 U insulin plus rHuPH20; Stage 2: insulin plus rHuPH20

Insulin Lispro Injection DRUG

injection

Also known as: Humalog®

Stage 3: 1.5 U insulin lispro plus rHuPH20; Stage 3: 6 U insulin lispro plus rHuPH20; Stage 4: 25 U/mL insulin lispro plus 5 μg/mL rHuPH20; Stage 4: 50 U/mL insulin lispro plus 5 μg/mL rHuPH20; Stage 4: 95 U/mL insulin lispro plus 5 μg/mL rHuPH20

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects between the ages of 18 and 55 years, inclusive. (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination (PE), including blood pressure (BP) and heart rate (HR), 12-lead electrocardiogram (ECG) and clinical laboratory tests specified in these eligibility criteria).
• BMI between 18-28 kg/m2, inclusive.
• Total body weight \>70 kg (154 lb) for men and 46 kg (101 lb) for women.
• Subject willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including adequate venous access.
• Vital signs (BP, HR, temperature, respiratory rate) within normal range or, if out of range, assessed by the Principal Investigator (PI) as not clinically significant (NCS) and mutually agreed by both PI and the Sponsor's medical monitor that the subject need not be excluded from the study for this abnormal value.
• Within 14 days before the first injection: metabolic panel (e.g., sodium, potassium, chloride, bicarbonate, BUN (blood urea nitrogen), creatinine, glucose, calcium, AST (aspartate transaminase \[SGOT\]), ALT (alanine transaminase \[SGPT\]), alkaline phosphatase, total bilirubin, albumin, cholesterol, lipids, amylase and total protein) and complete blood count (CBC) within the laboratory normal reference range or, if out of range, assessed by the PI as NCS and mutually agreed by both PI and the Sponsor's medical monitor that the subject need not be excluded from the study for this laboratory value.
• Fasting plasma glucose level within the range of 60 to 100 mg/dL, inclusive, within 30 minutes of the first euglycemic clamp.
• A negative serum pregnancy test (if female of childbearing potential) within 14 days of study drug injection.
• Female subjects of childbearing potential must agree to be practicing effective birth control or abstinence currently and agree to continue to do so for the duration of their time on study.
• Decision-making capacity and willingness and ability to comply with the requirements for full completion of the study.
• Signed, written IRB-approved informed consent.

You may not qualify if:

• 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 drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Clinical significance to be determined by the PI.
• Known history of diabetes mellitus or gestational diabetes.
• Known allergy to hyaluronidase or any other ingredient in the study drug.
• Positive HIV 1 and HIV 2 (human immunodeficiency virus) antibody test, hepatitis B (anti-HBsAg) 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, screening quantitative urine nicotine concentration \>50 ng/mL, or screening serum cotinine concentration of \> 20 ng/mL.
• Use of drugs that may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action or glucose utilization.
• 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.
• Participation in a study of any investigational drug or device 30 days before enrollment in this study.
• The subject is unfit for the study in the opinion of the investigator.
• Women who are pregnant or breast-feeding.

Sponsors & Collaborators

• Halozyme Therapeutics: lead

Study Sites (1)

dgd Research, Inc.

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Insulin; Insulin Lispro

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Short-Acting

Study Officials

• Jolene K Berg, MD

  dgd Research, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2008
• First Posted: December 8, 2008
• Study Start: November 1, 2008
• Primary Completion: August 28, 2009
• Study Completion: August 28, 2009
• Last Updated: August 15, 2018

Record last verified: 2018-08

Locations

US (1)