Phase II Pharmacokinetics Study of Humalog and Humulin-R With and Without rHuPH20 in Type 1 Diabetes Mellitus

NCT00774800 | Completed Phase 2 Results

• 2 other identifiers: HZ2-08-05HALO-117-201
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Humalog and Humulin-R (recombinant human insulin) are Food and Drug Administration (FDA) approved medications for the treatment of diabetes mellitus. Recombinant human hyaluronidase PH20 (rHuPH20) is approved by the FDA for use as an aid in the absorption and dispersion of other injectable drugs. In this study, rHuPH20 will be co-administered with both Humalog and Humulin-R in order to determine if it improves the absorption of these insulins to more closely mimic the body's natural increase in insulin in response to a meal.

Conditions

Type 1 Diabetes Mellitus

Keywords

Recombinant Hyaluronidase; Type 1 Diabetes Mellitus; Humalog; Humulin R; rHuPH20; Hylenex

Outcome Measures

Primary Outcomes (1)

• Area Under the Insulin Concentration-time Curve for the First Hour (AUC0-60)

  AUC was derived as the area under the serum insulin concentration profile from 0 to time "t." Samples were taken 30, 20, and 10 minutes (mins) prior to treatment; every 3 mins from mins 0 through 15; and at 20, 30, 45, and 60 mins postdose.

  Predose up to 60 minutes postdose

Secondary Outcomes (3)

• Maximum Serum Insulin Concentration (Cmax)

  Predose up to 480 minutes postdose

• Time to Maximum Serum Insulin Concentration (Tmax)

  Predose up to 480 minutes postdose

• Area Under the Blood Glucose Time-Concentration Curve Blood Glucose (AUC[BG])

  Predose up to 4 hours after injection of study drug

Study Arms (1)

First Humalog+PH20, then Humalog, Humulin-R+PH20, Humulin-R

EXPERIMENTAL

Humalog + Recombinant human hyaluronidase PH20 (rHuPH20) (Intervention 1): 24 units (U) of rHuPH20 per unit of Humalog, injected subcutaneously (SC), for up to 3 visits until an appropriate dose was identified. Humalog alone (Intervention 2): a single SC injection of the appropriate identified dose of Humalog, delivered before a liquid meal. Humulin-R + rHuPH20 (Intervention 3): 24 U of rHuPH20 per unit of Humulin-R, injected SC, for up to 2 visits until an appropriate dose was identified. Humulin-R alone (Intervention 4): a single SC injection of the appropriate identified dose of Humulin-R, delivered before a liquid meal. Appropriate dose of either Humalog or Humulin-R was that at which blood glucose following a liquid meal was \<160 milligrams per deciliter (mg/dL) for more than 30 minutes during the first 4 hours after injection and never fell below 60 mg/dL. All dose finding visits and interventions were separated by 3-10 days.

Drug: Humalog; Drug: Humulin-R; Drug: Recombinant human hyaluronidase PH20 (rHuPH20); Other: Liquid meal

Interventions

Humalog DRUG

Also known as: Insulin lispro

First Humalog+PH20, then Humalog, Humulin-R+PH20, Humulin-R

Humulin-R DRUG

Also known as: Humulin, Recombinant human insulin

First Humalog+PH20, then Humalog, Humulin-R+PH20, Humulin-R

Recombinant human hyaluronidase PH20 (rHuPH20) DRUG

Also known as: HYLENEX, PH20

First Humalog+PH20, then Humalog, Humulin-R+PH20, Humulin-R

Liquid meal OTHER

Also known as: Ensure

First Humalog+PH20, then Humalog, Humulin-R+PH20, Humulin-R

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female of age 18 to 65 years, inclusive. Females of child-bearing potential must use a standard and effective means of birth control for the duration of the study.
• Participants with Type 1 diabetes mellitus treated with insulin for greater than or equal to 12 months.
• Body mass index (BMI) 18.0 to 29.0 kilograms per meter squared (kg/m\^2), inclusive.
• Glycosylated hemoglobin A1c (HbA1c) less than or equal to 10% based on local laboratory results.
• Fasting C-peptide less than 0.6 nanograms per milliliter (ng/mL).
• Current treatment with insulin less than 1.2 units per kilogram per day (U/kg/day).
• Participants should be in good general health based on medical history and physical examination, without medical conditions that might prevent the completion of study drug injections and assessments required in this protocol.

You may not qualify if:

• Known or suspected allergy to any component of any of the study drugs in this trial.
• Previous enrollment in this trial.
• A participant who has proliferative retinopathy or maculopathy, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
• Clinically significant (as judged by the Investigator) active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on electrocardiogram \[ECG\]), hepatic, neurological, renal, genitourinary, or hematological systems, or uncontrolled hypertension (diastolic blood pressure greater than or equal to 100 millimeters of mercury \[mmHg\] and/or systolic blood pressure greater than or equal to 160 mmHg after 5 minutes in the supine position).
• History of any illness or disease that in the opinion of the Investigator might confound the results of the trial or pose additional risk in administering the study drugs to the participant.
• Clinically significant findings (as judged by the Investigator) in routine laboratory data, including anemia with hemoglobin less than lower limits of normal at screening.
• Use of drugs which may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia.
• Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator.
• Current addiction to alcohol or substances of abuse as determined by the Investigator.
• Blood donation (\>500 milliliters \[mL\]) within the 9 weeks prior to first day of dosing on study.
• Pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, intra-uterine device \[IUD\], oral or injectable contraceptives or barrier methods).
• Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation.
• Symptomatic gastroparesis.
• 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.
• Receipt of any investigational drug within 4 weeks of first day of dosing in this study.

Sponsors & Collaborators

• Halozyme Therapeutics: lead

Study Sites (1)

Profil Institute for Clinical Research, Inc.

Chula Vista, California, 91911, United States

Location

Related Publications (1)

• Hompesch M, Muchmore DB, Morrow L, Vaughn DE. Accelerated insulin pharmacokinetics and improved postprandial glycemic control in patients with type 1 diabetes after coadministration of prandial insulins with hyaluronidase. Diabetes Care. 2011 Mar;34(3):666-8. doi: 10.2337/dc10-1892. Epub 2011 Jan 27.

  PMID: 21273493 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Interventions

Insulin Lispro; Insulin; Insulin, Regular, Human

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Vice President, Endocrinology Clinical Development
• Organization: Halozyme Therapeutics, Inc.

(858) 794-8889

Study Officials

• Linda A Morrow, M.D.

  Profil Institute for Clinical Research, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2008
• First Posted: October 17, 2008
• Study Start: October 1, 2008
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: February 26, 2019
• Results First Posted: September 5, 2014

Record last verified: 2019-02

Locations

US (1)