Clinical trial NCT00705536: Pharmacokinetic (PK), Pharmacodynamic (PD), and Safety Study of Subcutaneously Administered Humalog® With and Without Recombinant Human Hyaluronidase (rHuPH20)and Humulin-R® With and Without rHuPH20
Official title: A Phase I, Randomized, Double-Blind Crossover Pharmacokinetic, Pharmacodynamic, and Safety Study of Subcutaneously Administered Humalog® (Insulin Lispro Injection; Rapid-Acting Insulin) With and Without Recombinant Human Hyaluronidase (rHuPH20) Versus Subcutaneously Administered Humulin R® (Regular Insulin Injection) With and Without rHuPH20
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus
Keywords: rHuPH20
Hyaluronidase
Insulin
Lead sponsor: Halozyme Therapeutics
Sponsor class: INDUSTRY
First posted: 2008-06-26
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The purpose of the study is to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of Humalog (insulin lispro) or Humulin-R (recombinant human insulin) when administered as a single subcutaneous (SC) injection of 20 units (U) with or without coadministration of recombinant human hyaluronidase PH20 (rHuPH20).

The study hypothesizes that the time required to reach maximum insulin concentration (tmax) when insulin is administered with rHuPH20 will be comparable or shorter than the time required without rHuPH20.


Eligibility criteria: Inclusion Criteria:

1. Healthy male participants aged 18 to 55 years.
2. Body mass index (BMI) 18 to 28 kilograms per meter squared (kg/m\^2) and total body weight \>70 kilograms (kg) (154 pounds \[lb\]).
3. Willingness and ability to comply with the protocol.
4. Vital signs within the normal range.
5. Within 7 days before the first injection, metabolic panel results and complete blood count (CBC) within the laboratory normal reference range.
6. Fasting plasma glucose within the normal range of 90 to 110 milligrams per deciliter (mg/dL) on the morning of the glucose clamp.
7. Agreement not to father a child or donate sperm and to use effective contraception during the study and for at least 30 days after study completion.
8. Willingness and ability to sign an informed consent form.

Exclusion Criteria:

1. Evidence or history of clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic (to include history of seizures) or allergic disease, or history of hypoglycemic episodes.
2. Known history of diabetes mellitus.
3. Prior exposure to any insulin or insulin analogs.
4. Known allergy to hyaluronidase or any other ingredient in HYLENEX.
5. Known allergy to bee or vespid venom.
6. Positive urine drug screen results.
7. Positive human immunodeficiency virus (HIV) 1, HIV 2, hepatitis B, or hepatitis C antibody test result.
8. Any history or evidence of alcohol or drug abuse.
9. History or evidence of use of any tobacco- or nicotine-containing product within 6 months of screening, or screening urine nicotine concentration \>50 nanograms per milliliter (ng/mL).
10. Use of prescription or nonprescription drugs within 7 days or 5 half-lives, whichever was shorter, except acetaminophen at doses of less than or equal to 1 gram per day (g/day).
11. Donation of blood in excess of 500 milliliters (mL) within 56 days before dosing.
12. Failure to limit alcohol consumption and refrain from exercise within 48 hours before each injection.
13. Known clinically significant intercurrent illness or other major systemic disease that would unduly risk the participant's safety or interfere with the interpretation of results.
14. Participation in a study of any investigational drug or device 30 days before enrollment in this study.
15. Unfitness for the study, in the investigator's opinion.

Primary outcomes:
measure: Time to Maximum Serum Insulin Concentration (Tmax)
timeFrame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
measure: Maximum Serum Insulin Concentration (Cmax)
timeFrame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
measure: Area Under the Serum Concentration-Time Curve From Time Zero to the Time Required to Reach Endogenous Plasma Glucose Levels (AUC[0-t'])
timeFrame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
measure: Area Under the Concentration-Time Curve From Time 0 to Time to Reach Maximum Concentration (Tmax) for Serum Insulin With Recombinant Human Hyaluronidase PH20 (rHuPH20) (AUC[0-tmaxPH20])
timeFrame: Predose and up to 48 minutes postdose during Stage 1, or up to 68 minutes postdose during Stage 2
measure: Relative Bioavailability (Area Under the Curve [AUC] for Insulin + Recombinant Human Hyaluronidase [rHuPH20] / AUC for Insulin Alone)
timeFrame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Secondary outcomes:
measure: Time to Maximum Glucose Infusion Rate (tGIR[Max])
timeFrame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
measure: Time to Early Half-Maximal Effect for Glucose Infusion Rate (tGIR[early50%])
timeFrame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
measure: Time to Late Half-Maximal Effect for Glucose Infusion Rate (tGIR[late50%])
timeFrame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
measure: Maximum Glucose Infusion Rate (GIR[Max])
timeFrame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
measure: Area Under the Glucose Infusion Rate Curve From 0 to 60 Minutes After Injection (AUC[GIR{0-60}])
timeFrame: Predose and up to 60 minutes postdose during Stage 1 or Stage 2
measure: Area Under the Glucose Infusion Rate Curve From 0 to 120 Minutes After Injection (AUC[GIR{0-120}])
timeFrame: Predose and up to 120 minutes postdose during Stage 1 or Stage 2
measure: Area Under the Glucose Infusion Rate Curve From 0 to 180 Minutes After Injection (AUC[GIR{0-180}])
timeFrame: Predose and up to 180 minutes postdose during Stage 1 or Stage 2
measure: Area Under the Glucose Infusion Rate Curve From 0 to 240 Minutes After Injection (AUC[GIR{0-240}])
timeFrame: Predose up to 240 minutes postdose during Stage 1 or Stage 2
measure: Area Under the Glucose Infusion Rate Curve From 0 to 360 Minutes After Injection (AUC[GIR{0-360}])
timeFrame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Diabetes and Glandular Disease Research, Inc.
state: Texas
Study officials:
affiliation: Diabetes and Glandular Disease Research Associates Inc.
name: Mark S. Kipnes, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vaughn DE, Yocum RC, Muchmore DB, Sugarman BJ, Vick AM, Bilinsky IP, Frost GI. Accelerated pharmacokinetics and glucodynamics of prandial insulins injected with recombinant human hyaluronidase. Diabetes Technol Ther. 2009 Jun;11(6):345-52. doi: 10.1089/dia.2009.0013.