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Completed

NCT Number: NCT00916357

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 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.

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Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Profil Institute for Clinical Research, Inc.

Chula Vista, California, 91911, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Humalog

Drug

Other names: Insulin lispro

Humulin-R

Drug

Other names: Humulin, Regular human insulin

Recombinant human hyaluronidase PH20 (rHuPH20)

Drug

Other names: PH20, HYLENEX

Primary outcomes

  1. Postprandial Glucose (PPG) Excursion Following a Liquid Meal

    Time frame: Predose up to 480 minutes after study drug injection

    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 outcomes

  1. Maximum Serum Insulin Concentration (Cmax)

    Time frame: Predose up to 480 minutes after study drug injection

    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.

  2. Time To Maximum Serum Insulin Concentration (Tmax)

    Time frame: Predose up to 480 minutes after study drug injection

    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.

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

    Time frame: Predose up to 120 minutes after study drug injection

    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.

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

    Time frame: Predose up to 480 minutes after study drug injection

    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.

  5. 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

    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.

  6. 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

    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.

  7. Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG])

    Time frame: Predose up to 480 minutes after study drug injection

    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.

  8. Minimum Postprandial Glucose (PPG)

    Time frame: Predose up to 480 minutes after study drug injection

    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.

  9. Percentage of Participants Without Hypoglycemia

    Time frame: Predose up to 480 minutes after study drug injection

    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.

  10. 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

    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.

Sponsors and collaborators

Lead sponsor

Halozyme Therapeutics

Industry

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2009
Study completion
2009
First posted
Jun 9, 2009
Registry last updated
Aug 18, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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