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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT00916357
First received: June 5, 2009
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Humalog
Drug: Humulin-R
Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Phase 2, Double-Blind Randomized, 3-way Cross-Over Liquid Meal Study With Optimal Doses of SC Administered Insulin Lispro With and Without rHuPH20 and Regular Human Insulin With rHuPH20 to Compare Pharmacokinetics, Postprandial Glycemic Response, and Optimal Insulin Dose in Patients With T2DM

Resource links provided by NLM:


Further study details as provided by Halozyme Therapeutics:

Primary Outcome Measures:
  • Postprandial Glucose (PPG) Excursion Following a Liquid Meal [ Time Frame: Predose up to 480 minutes after study drug injection ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Maximum Serum Insulin Concentration (Cmax) [ Time Frame: Predose up to 480 minutes after study drug injection ] [ Designated as safety issue: No ]
    Maximum serum insulin concentration (Cmax) for participants receiving Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 is 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.

  • Time To Maximum Serum Insulin Concentration (Tmax) [ Time Frame: Predose up to 480 minutes after study drug injection ] [ Designated as safety issue: No ]
    Time to maximum serum insulin concentration (Tmax) for participants receiving Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 following a liquid meal is 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.

  • Time to Early 50% Maximum Serum Insulin Concentration (Early[t50%]) [ Time Frame: Predose up to 120 minutes after study drug injection ] [ Designated as safety issue: No ]
    Time to early 50% maximum serum insulin concentration (early[t50%]) for participants receiving Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 following a liquid meal is 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, and 120 minutes after injection of each study drug.

  • Time to Late 50% Maximum Serum Insulin Concentration (Late[t50%]) [ Time Frame: Predose up to 480 minutes after study drug injection ] [ Designated as safety issue: No ]
    Time to late 50% maximum serum insulin concentration (late[t50%]) for participants receiving Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 following a liquid meal is 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.

  • Mean Residence Time From Time 0 to the End of Blood Sampling (MRT[Last]) [ Time Frame: Predose up to 480 minutes after study drug injection ] [ Designated as safety issue: No ]
    Mean residence time from time 0 to the end of blood sampling (MRT[last]) for participants who received Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 following a liquid meal is 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.

  • Area Under the Concentration Time-Curve for Serum Insulin From Time 0 to the End of Blood Sampling (AUC[Last]) [ Time Frame: Predose up to 480 minutes after study drug injection ] [ Designated as safety issue: No ]
    Area under the concentration time-curve for serum insulin from time 0 to the end of blood sampling (AUC[last]) for participants who received Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 during a liquid meal is 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 squares mean difference was calculated and tested using repeated measures analysis of variance with fixed effect for treatment.

  • Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG]) [ Time Frame: Predose up to 480 minutes after study drug injection ] [ Designated as safety issue: No ]
    Area under the time-concentration curve for blood glucose (AUC[BG]) for participants who received Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), and Humulin-R + rHuPH20 following a liquid meal is reported. AUC(BG) values are reported for participants whose blood glucose (BG) was elevated higher than 160 milligrams per deciliter (mg/dL) or 140 mg/dL, or lower than 70 mg/dL within 4 hours of consuming a liquid meal. 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 squares mean difference was calculated and tested using repeated measures analysis of variance with fixed effect for treatment.

  • Minimum Postprandial Glucose (PPG) [ Time Frame: Predose up to 480 minutes after study drug injection ] [ Designated as safety issue: No ]
    Minimum postprandial glucose (PPG) in participants who received Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 following a liquid meal is 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.

  • Percentage of Participants Without Hypoglycemia [ Time Frame: Predose up to 480 minutes after study drug injection ] [ Designated as safety issue: No ]
    Percentage of participants who received Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 who did not experience hypoglycemia following a liquid meal is reported. Hypoglycemia was defined as any blood glucose values lower than 70 milligrams per deciliter (mg/dL) or symptoms of hypoglycemia responding to treatment with glucose. 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.

  • Time to Percentage of Insulin Exposure (as Measured by Area Under the Curve [AUC]) [ Time Frame: Predose up to 480 minutes following after injection of study drug ] [ Designated as safety issue: No ]
    Time to percentage of exposure to insulin, as measured by area under the curve (AUC), following a liquid meal for participants who received Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 is 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.


Enrollment: 23
Study Start Date: July 2009
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Humalog, Then Humalog + rHuPH20, Then Humulin-R + rHuPH20
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
Other Name: Insulin lispro
Drug: Humulin-R
Other Names:
  • Humulin
  • Regular human insulin
Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Other Names:
  • PH20
  • HYLENEX
Active Comparator: Humalog, Then Humulin-R + rHuPH20, Then Humalog + rHuPH20
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
Other Name: Insulin lispro
Drug: Humulin-R
Other Names:
  • Humulin
  • Regular human insulin
Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Other Names:
  • PH20
  • HYLENEX
Active Comparator: Humalog + rHuPH20, Then Humalog, Then Humulin-R + rHuPH20
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
Other Name: Insulin lispro
Drug: Humulin-R
Other Names:
  • Humulin
  • Regular human insulin
Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Other Names:
  • PH20
  • HYLENEX
Active Comparator: Humalog + rHuPH20, Then Humulin-R + rHuPH20, Then Humalog
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
Other Name: Insulin lispro
Drug: Humulin-R
Other Names:
  • Humulin
  • Regular human insulin
Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Other Names:
  • PH20
  • HYLENEX
Active Comparator: Humulin-R + rHuPH20, Then Humalog, Then Humalog + rHuPH20
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
Other Name: Insulin lispro
Drug: Humulin-R
Other Names:
  • Humulin
  • Regular human insulin
Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Other Names:
  • PH20
  • HYLENEX
Active Comparator: Humulin-R + rHuPH20, Then Humalog + rHuPH20, Then Humalog
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
Other Name: Insulin lispro
Drug: Humulin-R
Other Names:
  • Humulin
  • Regular human insulin
Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Other Names:
  • PH20
  • HYLENEX

Detailed Description:

This study design was chosen to assess the differences between pharmacokinetic (PK) and pharmacodynamic (PD) parameters, including postprandial glycemic response, of Humalog + recombinant human hyaluronidase PH20 (rHuPH20), Humalog alone, and Humulin-R + rHuPH20 at optimal doses following a liquid meal.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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).
  • As judged by the Investigator, clinically significant findings in routine laboratory data (anemia with hematocrit less than 33% at screening is specifically exclusionary)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00916357

Locations
United States, California
Profil Institute for Clinical Research, Inc.
Chula Vista, California, United States, 91911
Sponsors and Collaborators
Halozyme Therapeutics
Investigators
Principal Investigator: Marcus Hompesch, M.D. Profil Institute for Clinical Research, Inc.
  More Information

Publications:
Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT00916357     History of Changes
Other Study ID Numbers: HALO-117-204
Study First Received: June 5, 2009
Results First Received: July 30, 2014
Last Updated: July 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Halozyme Therapeutics:
recombinant human hyaluronidase PH20 (rHuPH20)
Insulin lispro
Regular human insulin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin
Insulin Lispro
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014