Liquid Meal Study With Insulin Lispro With/Without Recombinant Human Hyaluronidase PH20 (rHuPH20) and Regular Human Insulin With rHuPH20 to Compare Pharmacokinetics, Postprandial Glycemic Response, and Optimal Insulin Dose in Participants With Type 2 Diabetes Mellitus (T2DM)

NCT00916357 | Completed Phase 2 Results

• 1 other identifier: HALO-117-204
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, Phase 2, randomized, double-blind, 3-way crossover meal study in participants with Type 2 Diabetes Mellitus (T2DM) to determine the optimum dose and compare the pharmacokinetics (PK) and postprandial glycemic response of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), and Humulin-R + rHuPH20 administered subcutaneously.

Conditions

Diabetes Mellitus, Type 2

Keywords

recombinant human hyaluronidase PH20 (rHuPH20); Insulin lispro; Regular human insulin

Outcome Measures

Primary Outcomes (1)

• Postprandial Glucose (PPG) Excursion Following a Liquid Meal

  Postprandial glucose (PPG) values in participants receiving Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 following a liquid meal are reported. Blood samples were collected at 30, 20, 10, and within 5 minutes before and at 3, 6, 9, 12, 15, 20, 25, 30, 45, 60, 75, 90, 120, 150, 180, 210, 240, 300, 360, 420, and 480 minutes after injection of each study drug. Least square mean difference was calculated and tested using repeated measures analysis of variance with fixed effect for treatment.

  Predose up to 480 minutes after study drug injection

Secondary Outcomes (10)

• Maximum Serum Insulin Concentration (Cmax)

  Predose up to 480 minutes after study drug injection

• Time To Maximum Serum Insulin Concentration (Tmax)

  Predose up to 480 minutes after study drug injection

• Time to Early 50% Maximum Serum Insulin Concentration (Early[t50%])

  Predose up to 120 minutes after study drug injection

• Time to Late 50% Maximum Serum Insulin Concentration (Late[t50%])

  Predose up to 480 minutes after study drug injection

• Mean Residence Time From Time 0 to the End of Blood Sampling (MRT[Last])

  Predose up to 480 minutes after study drug injection

Study Arms (6)

Humalog, Then Humalog + rHuPH20, Then Humulin-R + rHuPH20

ACTIVE COMPARATOR

A subcutaneous (SC) injection of 0.3- to 0.5-units per kilogram (U/kg) of Humalog alone for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout period), followed by a SC injection of the appropriate dose of Humalog. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog + 3.75 nanograms/kilogram (ng/kg) recombinant human hyaluronidase PH20 (rHuPH20). The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 ng/kg rHuPH20 following a 3 to 14 day washout period.

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

Humalog, Then Humulin-R + rHuPH20, Then Humalog + rHuPH20

ACTIVE COMPARATOR

A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog alone for up to 3 dose finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 nanograms/kilogram (ng/kg) recombinant human hyaluronidase PH20 (rHuPH20). The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period.

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

Humalog + rHuPH20, Then Humalog, Then Humulin-R + rHuPH20

ACTIVE COMPARATOR

A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog + 3.75 nanograms per kilogram (ng/kg) recombinant human hyaluronidase PH20(rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog alone. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period.

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

Humalog + rHuPH20, Then Humulin-R + rHuPH20, Then Humalog

ACTIVE COMPARATOR

A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humulin-R + rHuPH20. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog following a 3- to 14-day washout period.

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

Humulin-R + rHuPH20, Then Humalog, Then Humalog + rHuPH20

ACTIVE COMPARATOR

A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humulin-R + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humulin-R + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog alone. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period.

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

Humulin-R + rHuPH20, Then Humalog + rHuPH20, Then Humalog

ACTIVE COMPARATOR

A subcutaneous (SC) injection of 0.3- to 0.5-units per kilogram (U/kg) of Humulin-R + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humulin-R + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog alone following a 3- to 14-day washout period.

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

Interventions

Humalog DRUG

Also known as: Insulin lispro

Humalog + rHuPH20, Then Humalog, Then Humulin-R + rHuPH20; Humalog + rHuPH20, Then Humulin-R + rHuPH20, Then Humalog; Humalog, Then Humalog + rHuPH20, Then Humulin-R + rHuPH20; Humalog, Then Humulin-R + rHuPH20, Then Humalog + rHuPH20; Humulin-R + rHuPH20, Then Humalog + rHuPH20, Then Humalog; Humulin-R + rHuPH20, Then Humalog, Then Humalog + rHuPH20

Humulin-R DRUG

Also known as: Humulin, Regular human insulin

Humalog + rHuPH20, Then Humalog, Then Humulin-R + rHuPH20; Humalog + rHuPH20, Then Humulin-R + rHuPH20, Then Humalog; Humalog, Then Humalog + rHuPH20, Then Humulin-R + rHuPH20; Humalog, Then Humulin-R + rHuPH20, Then Humalog + rHuPH20; Humulin-R + rHuPH20, Then Humalog + rHuPH20, Then Humalog; Humulin-R + rHuPH20, Then Humalog, Then Humalog + rHuPH20

Recombinant human hyaluronidase PH20 (rHuPH20) DRUG

Also known as: PH20, HYLENEX

Humalog + rHuPH20, Then Humalog, Then Humulin-R + rHuPH20; Humalog + rHuPH20, Then Humulin-R + rHuPH20, Then Humalog; Humalog, Then Humalog + rHuPH20, Then Humulin-R + rHuPH20; Humalog, Then Humulin-R + rHuPH20, Then Humalog + rHuPH20; Humulin-R + rHuPH20, Then Humalog + rHuPH20, Then Humalog; Humulin-R + rHuPH20, Then Humalog, Then Humalog + rHuPH20

Eligibility Criteria

• Age: 18 Years - 70 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 70 years, inclusive
• Participants with Type 2 diabetes mellitus (T2DM) per World Health Organization criteria treated with basal and/or bolus insulin for ≥12 months.
• Body mass index (BMI) between 18 to 45 kilograms per square meter (kg/m\^2), inclusive
• Glycosylated hemoglobin A1c (HbA1c) ≤10%
• Current treatment with insulin ≥60 Units/day (U/d)
• A participant taking oral hypoglycemic agents must be on a stable dose for \>8 weeks with the exception of thiazolidinediones (TZD), which should be \>12 weeks.
• Total body weight \>65 kilograms (kg) (143 pounds \[lb\]) for men and \>46 kg (101 lb) for women
• Vital signs (blood pressure \[BP\], pulse rate, and body temperature) within normal range or, if out of range, assessed by the Investigator as not clinically significant (NCS)
• 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 in this protocol
• Decision making capacity and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including adequate venous access.
• Signed and written Internal Review Board-approved informed consent

You may not qualify if:

• Known or suspected allergy to any components of any of the study drugs in this study
• Previous enrollment in this study
• A participant who has proliferative retinopathy, proliferative maculopathy, and/or severe neuropathy (in particular, autonomic neuropathy) as judged by the Investigator
• As judged by the Investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on electrocardiogram \[ECG\] and New York Heart Association \[NYHA\] Class III/IV heart disease), hepatic, neurological, renal, genitourinary, or hematological systems
• As judged by the Investigator, uncontrolled hypertension (diastolic BP ≥100 millimeters of mercury \[mmHg\] and/or systolic BP ≥160 mmHg after 5 minutes in the supine position).
• Positive human immunodeficiency virus (HIV) antibody test, hepatitis B (anti-HBsAg), or hepatitis C (anti-HCV) antibody test
• Current addiction to alcohol or substances of abuse as determined by the Investigator
• Known use of drugs (other than oral hypoglycemic agents) that may interfere with the interpretation of study 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 determined by the Investigator
• Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study
• Symptomatic gastroparesis
• Donation of blood in excess of 500 milliliters (mL) within 56 days before dosing
• Use of any investigational drug or device 30 days before enrollment in this 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, barrier methods, or remaining abstinent)
• Any condition (intrinsic or extrinsic) that, in the judgment of the Investigator, will interfere with study participation or evaluation of data

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, Ludington E, Vaughn DE. Improved postprandial glycemic control in patients with type 2 diabetes from subcutaneous injection of insulin lispro with hyaluronidase. Diabetes Technol Ther. 2012 Mar;14(3):218-24. doi: 10.1089/dia.2011.0117. Epub 2011 Dec 2.

  PMID: 22136324 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; 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; 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

858-794-8889

Study Officials

• Marcus Hompesch, M.D.

  Profil Institute for Clinical Research, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2009
• First Posted: June 9, 2009
• Study Start: July 1, 2009
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: August 18, 2014
• Results First Posted: August 18, 2014

Record last verified: 2014-07

Locations

US (1)