Clinical trial NCT00979875: A Pharmacokinetic and Glucodynamic Study of Subcutaneously Administered Insulin Analogs With rHuPH20 Compared to Insulin Analogs Alone
Official title: Phase 1, Randomized, Double-Blind, Pharmacokinetic and Glucodynamic, 6-Way Crossover Study of Subcutaneously Administered Insulin Analogs With Recombinant Human Hyaluronidase (rHuPH20) Compared to Insulin Analogs Alone in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: insulin
recombinant human hyaluronidase
Healthy volunteers
Lead sponsor: Halozyme Therapeutics
Sponsor class: INDUSTRY
First posted: 2009-09-18
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.


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.

Primary outcomes:
measure: Area Under the Concentration-time Curve for Serum Insulin From Time 0 to 60 Minutes (AUC0-60)
timeFrame: Predose up to 60 minutes postdose
Secondary outcomes:
measure: Time to Maximum Serum Insulin Concentration (Tmax)
timeFrame: Predose up to 480 minutes postdose
measure: Time to Early and Late 50% Maximum Serum Insulin Concentration (t[50%Max])
timeFrame: Predose up to 480 minutes postdose
measure: Time to Maximum Glucose Infusion Rate (tGIR[Max])
timeFrame: Predose up to 480 minutes postdose
measure: Percentage of Total Area Under the Concentration-time Curve for Serum Insulin Attained by Time t (AUC0-t)
timeFrame: Predose up to 120 minutes postdose
measure: Time to Percentage of Total Insulin Exposure
timeFrame: Predose up to 480 minutes postdose
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research, Inc.
state: California
Study officials:
affiliation: Profil Institute for Clinical Research, Inc.
name: Marcus Hompesch, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.