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

NCT00705536 | Completed Phase 1 Results

• 1 other identifier: HZ2-07-04
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus

Keywords

rHuPH20; Hyaluronidase; Insulin

Outcome Measures

Primary Outcomes (5)

• Time to Maximum Serum Insulin Concentration (Tmax)

  Time to maximum serum insulin concentration (tmax) values for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from 3 milliliter (mL) blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.

  Predose and up to 360 minutes postdose during Stage 1 or Stage 2

• Maximum Serum Insulin Concentration (Cmax)

  Maximum serum insulin concentration (Cmax) values for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from 3 milliliter (mL) blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.

  Predose and up to 360 minutes postdose during Stage 1 or Stage 2

• Area Under the Serum Concentration-Time Curve From Time Zero to the Time Required to Reach Endogenous Plasma Glucose Levels (AUC[0-t'])

  Area under the serum concentration-time curve from time zero to the time required to reach endogenous plasma glucose levels (AUC\[0-t'\]) for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from 3 milliliter (mL) blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.

  Predose and up to 360 minutes postdose during Stage 1 or Stage 2

• 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])

  Area under the concentration-time curve from time 0 to time to reach maximum concentration (tmax) for serum insulin (Humalog or Humulin-R) with recombinant human hyaluronidase (rHuPH20) (AUC\[0-tmaxPH20\]) for participants who received Humalog or Humulin-R and with rHuPH20 were measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment and every 3 min from min 0 through 48 for Stage 1 and, and every 3 min from min 0 through 68 for Stage 2 during the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.

  Predose and up to 48 minutes postdose during Stage 1, or up to 68 minutes postdose during Stage 2

• Relative Bioavailability (Area Under the Curve [AUC] for Insulin + Recombinant Human Hyaluronidase [rHuPH20] / AUC for Insulin Alone)

  Relative bioavailability was determined by dividing the baseline-corrected geometric mean of the area under the curve (AUC) for insulin (ins) (Humalog or Humulin-R) with recombinant human hyaluronidase PH20 (rHuPH20) by the baseline-corrected geometric mean of the AUC for insulin alone (AUC\[insulin+rHuPH20\]/AUC\[insulin\]). Bioavailability values for participants who received Humalog or Humulin-R and rHuPH20 were measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.

  Predose and up to 360 minutes postdose during Stage 1 or Stage 2

Secondary Outcomes (9)

• Time to Maximum Glucose Infusion Rate (tGIR[Max])

  Predose and up to 360 minutes postdose during Stage 1 or Stage 2

• Time to Early Half-Maximal Effect for Glucose Infusion Rate (tGIR[early50%])

  Predose and up to 360 minutes postdose during Stage 1 or Stage 2

• Time to Late Half-Maximal Effect for Glucose Infusion Rate (tGIR[late50%])

  Predose and up to 360 minutes postdose during Stage 1 or Stage 2

• Maximum Glucose Infusion Rate (GIR[Max])

  Predose and up to 360 minutes postdose during Stage 1 or Stage 2

• Area Under the Glucose Infusion Rate Curve From 0 to 60 Minutes After Injection (AUC[GIR{0-60}])

  Predose and up to 60 minutes postdose during Stage 1 or Stage 2

Study Arms (4)

Humalog first, then Humalog + rHuPH20

ACTIVE COMPARATOR

Humalog first, then Humalog + recombinant human hyaluronidase PH20 (rHuPH20) A single subcutaneous (SC) injection of 20 units (U) Humalog on Day 1 of the study, followed by a single SC injection of 20 U Humalog + 300 U rHuPH20 after a washout period of at least 6 days

Drug: Humalog; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

Humalog + rHuPH20 first, then Humalog

ACTIVE COMPARATOR

Humalog + recombinant human hyaluronidase PH20 (rHuPH20) first, then Humalog A single subcutaneous (SC) injection of 20 units (U) Humalog + 300 U rHuPH20 on Day 1 of the study, followed by a single SC injection of 20 U Humalog after a washout period of at least 6 days

Drug: Humalog; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

Humulin-R first, then Humulin-R + rHuPH20

ACTIVE COMPARATOR

Humulin-R (recombinant human insulin) first, then Humulin-R + recombinant human hyaluronidase PH20 (rHuPH20) A single subcutaneous (SC) injection of 20 units (U) Humulin-R on Day 1 of the study, followed by a single SC injection of 20 U Humulin-R + 240 U rHuPH20 after a washout period of at least 6 days

Drug: Humulin-R; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

Humulin-R + rHuPH20 first, then Humulin-R

ACTIVE COMPARATOR

Humulin-R (recombinant human insulin) + recombinant human hyaluronidase PH20 (rHuPH20) first, then Humulin-R A single subcutaneous (SC) injection of 20 units (U) Humulin-R + 240 U rHuPH20 on Day 1 of the study, followed by a single SC injection of 20 U Humulin-R after a washout period of at least 6 days

Drug: Humulin-R; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

Interventions

Humalog DRUG

Also known as: Insulin lispro

Humalog + rHuPH20 first, then Humalog; Humalog first, then Humalog + rHuPH20

Humulin-R DRUG

Also known as: Humulin, Recombinant human insulin

Humulin-R + rHuPH20 first, then Humulin-R; Humulin-R first, then Humulin-R + rHuPH20

Recombinant human hyaluronidase PH20 (rHuPH20) DRUG

Also known as: PH20, HYLENEX

Humalog + rHuPH20 first, then Humalog; Humalog first, then Humalog + rHuPH20; Humulin-R + rHuPH20 first, then Humulin-R; Humulin-R first, then Humulin-R + rHuPH20

Eligibility Criteria

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

You may qualify if:

• Healthy male participants aged 18 to 55 years.
• Body mass index (BMI) 18 to 28 kilograms per meter squared (kg/m\^2) and total body weight \>70 kilograms (kg) (154 pounds \[lb\]).
• Willingness and ability to comply with the protocol.
• Vital signs within the normal range.
• Within 7 days before the first injection, metabolic panel results and complete blood count (CBC) within the laboratory normal reference range.
• Fasting plasma glucose within the normal range of 90 to 110 milligrams per deciliter (mg/dL) on the morning of the glucose clamp.
• 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.
• Willingness and ability to sign an informed consent form.

You may not qualify if:

• 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.
• Known history of diabetes mellitus.
• Prior exposure to any insulin or insulin analogs.
• Known allergy to hyaluronidase or any other ingredient in HYLENEX.
• Known allergy to bee or vespid venom.
• Positive urine drug screen results.
• Positive human immunodeficiency virus (HIV) 1, HIV 2, hepatitis B, or hepatitis C antibody test result.
• 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, or screening urine nicotine concentration \>50 nanograms per milliliter (ng/mL).
• 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).
• Donation of blood in excess of 500 milliliters (mL) within 56 days before dosing.
• Failure to limit alcohol consumption and refrain from exercise within 48 hours before each injection.
• 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.
• Participation in a study of any investigational drug or device 30 days before enrollment in this study.
• Unfitness for the study, in the investigator's opinion.

Sponsors & Collaborators

• Halozyme Therapeutics: lead

Study Sites (1)

Diabetes and Glandular Disease Research, Inc.

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• 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.

  PMID: 19459762 RESULT

MeSH Terms

Conditions

Diabetes Mellitus; Insulin Resistance

Interventions

Insulin Lispro; Insulin; Insulin, Regular, Human

Condition Hierarchy (Ancestors)

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

• Mark S. Kipnes, MD

  Diabetes and Glandular Disease Research Associates Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2008
• First Posted: June 26, 2008
• Study Start: December 1, 2007
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2008
• Last Updated: February 26, 2019
• Results First Posted: July 14, 2014

Record last verified: 2019-02

Locations

US (1)