Diabetes Mellitus, Type 2
Conditions
Keywords
recombinant human hyaluronidase PH20 (rHuPH20), Insulin lispro, Regular human insulin
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.
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.
Interventions
Sponsors
Halozyme Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postprandial Glucose (PPG) Excursion Following a Liquid Meal | 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
| Measure | Time frame | Description |
|---|---|---|
| Time To Maximum Serum Insulin Concentration (Tmax) | 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. |
| Time to Early 50% Maximum Serum Insulin Concentration (Early[t50%]) | 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. |
| Time to Late 50% Maximum Serum Insulin Concentration (Late[t50%]) | 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. |
| Mean Residence Time From Time 0 to the End of Blood Sampling (MRT[Last]) | 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. |
| Maximum Serum Insulin Concentration (Cmax) | 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. |
| Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG]) | 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. |
| Minimum Postprandial Glucose (PPG) | 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. |
| Percentage of Participants Without Hypoglycemia | 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. |
| Time to Percentage of Insulin Exposure (as Measured by Area Under the Curve [AUC]) | 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. |
| Area Under the Concentration Time-Curve for Serum Insulin From Time 0 to the End of Blood Sampling (AUC[Last]) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Participants who received at least 1 dose of Humalog, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 during dose-finding (DV) visits or experimental (data gathering) visits. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 2 | Weight loss > 3 kilograms (kg) | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 52.2 Years (yr) STANDARD_DEVIATION 8.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment United States | 23 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 22 | 5 / 22 | 10 / 22 |
| serious Total, serious adverse events | 0 / 22 | 1 / 22 | 0 / 22 |
Outcome results
Primary
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.
Time frame: Predose up to 480 minutes after study drug injection
Population: Participants who received at least 1 dose of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 with evaluable postprandial glucose (PPG) excursion data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Humalog Alone | Postprandial Glucose (PPG) Excursion Following a Liquid Meal | 60-minute PPG | 162.71 Milligrams per deciliter (mg/dL) | Standard Deviation 32.28 |
| Humalog Alone | Postprandial Glucose (PPG) Excursion Following a Liquid Meal | 90-minute PPG | 166.05 Milligrams per deciliter (mg/dL) | Standard Deviation 34.53 |
| Humalog Alone | Postprandial Glucose (PPG) Excursion Following a Liquid Meal | 120-minute PPG | 159.10 Milligrams per deciliter (mg/dL) | Standard Deviation 30.73 |
| Humalog Alone | Postprandial Glucose (PPG) Excursion Following a Liquid Meal | CBGMax(0-4hr) | 177.81 Milligrams per deciliter (mg/dL) | Standard Deviation 33.46 |
| Humalog + rHuPH20 | Postprandial Glucose (PPG) Excursion Following a Liquid Meal | CBGMax(0-4hr) | 165.38 Milligrams per deciliter (mg/dL) | Standard Deviation 21.39 |
| Humalog + rHuPH20 | Postprandial Glucose (PPG) Excursion Following a Liquid Meal | 60-minute PPG | 144.67 Milligrams per deciliter (mg/dL) | Standard Deviation 28.08 |
| Humalog + rHuPH20 | Postprandial Glucose (PPG) Excursion Following a Liquid Meal | 120-minute PPG | 138.24 Milligrams per deciliter (mg/dL) | Standard Deviation 32.34 |
| Humalog + rHuPH20 | Postprandial Glucose (PPG) Excursion Following a Liquid Meal | 90-minute PPG | 143.62 Milligrams per deciliter (mg/dL) | Standard Deviation 30.75 |
| Humulin-R + rHuPH20 | Postprandial Glucose (PPG) Excursion Following a Liquid Meal | CBGMax(0-4hr) | 181.62 Milligrams per deciliter (mg/dL) | Standard Deviation 31.61 |
| Humulin-R + rHuPH20 | Postprandial Glucose (PPG) Excursion Following a Liquid Meal | 90-minute PPG | 166.71 Milligrams per deciliter (mg/dL) | Standard Deviation 33.83 |
| Humulin-R + rHuPH20 | Postprandial Glucose (PPG) Excursion Following a Liquid Meal | 120-minute PPG | 159.90 Milligrams per deciliter (mg/dL) | Standard Deviation 39.56 |
| Humulin-R + rHuPH20 | Postprandial Glucose (PPG) Excursion Following a Liquid Meal | 60-minute PPG | 169.38 Milligrams per deciliter (mg/dL) | Standard Deviation 28.64 |
Comparison: 60 minutes after study drug injection.p-value: 0.0034Repeated Measures Analysis of Variance
Comparison: 60 minutes after study drug injection.p-value: 0.26Repeated Measures Analysis of Variance
Comparison: 60 minutes after study drug injection.p-value: 0.0001Repeated measures Analysis of Variance
Comparison: 90 minutes after study drug injection.p-value: 0.0039Repeated Measures Analysis of Variance
Comparison: 90 minutes after study drug injection.p-value: 0.93Repeated Measures Analysis of Variance
Comparison: 90 minutes after study drug injection.p-value: 0.0031Repeated Measures Analysis of Variance
Comparison: 120 minutes after study drug injection.p-value: 0.019Repeated Measures Analysis of Variance
Comparison: 120 minutes after study drug injection.p-value: 0.92Repeated Measures Analysis of Variance
Comparison: 120 minutes after study drug injection.p-value: 0.015Repeated Measures Analysis of Variance
Comparison: Peak postprandial glucose (PPG) values.p-value: 0.095Repeated Measures Analysis of Variance
Comparison: Peak postprandial glucose (PPG) values.p-value: 0.6Repeated Measures Analysis of Variance
Comparison: Peak postprandial glucose (PPG) values.p-value: 0.031Repeated Measures Analysis of Variance
Secondary
Area Under the Concentration Time-Curve for Serum Insulin From Time 0 to the End of Blood Sampling (AUC[Last])
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.
Time frame: Predose up to 480 minutes after study drug injection
Population: Participants who received at least 1 dose of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 with evaluable area under the concentration time-curve for serum insulin from time 0 to the end of blood sampling (AUC\[last\]) data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Humalog Alone | Area Under the Concentration Time-Curve for Serum Insulin From Time 0 to the End of Blood Sampling (AUC[Last]) | 578.67 Minutes * picomoles /1000 (min*pm/1000) | Standard Deviation 144.66 |
| Humalog + rHuPH20 | Area Under the Concentration Time-Curve for Serum Insulin From Time 0 to the End of Blood Sampling (AUC[Last]) | 668.33 Minutes * picomoles /1000 (min*pm/1000) | Standard Deviation 146.52 |
| Humulin-R + rHuPH20 | Area Under the Concentration Time-Curve for Serum Insulin From Time 0 to the End of Blood Sampling (AUC[Last]) | 571.42 Minutes * picomoles /1000 (min*pm/1000) | Standard Deviation 132.04 |
p-value: 0.01Repeated Measures Analysis of Variance
p-value: 0.82Repeated Measures Analysis of Variance
p-value: 0.0056Repeated Measures Analysis of Variance
Secondary
Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG])
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.
Time frame: Predose up to 480 minutes after study drug injection
Population: Participants who received at least 1 dose of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 with evaluable area under the time-concentration curve for blood glucose (AUC\[BG\]) data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Humalog Alone | Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG]) | AUC(BG) >140 mg/dL | 4233.71 Milligrams per deciliter * minutes | Standard Deviation 4383.35 |
| Humalog Alone | Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG]) | AUC(BG) >160 mg/dL | 2017.46 Milligrams per deciliter * minutes | Standard Deviation 2811.82 |
| Humalog Alone | Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG]) | AUC(BG) <70 mg/dL | 571.20 Milligrams per deciliter * minutes | Standard Deviation 850.07 |
| Humalog + rHuPH20 | Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG]) | AUC(BG) >140 mg/dL | 2696.54 Milligrams per deciliter * minutes | Standard Deviation 2548.03 |
| Humalog + rHuPH20 | Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG]) | AUC(BG) >160 mg/dL | 722.82 Milligrams per deciliter * minutes | Standard Deviation 1030.52 |
| Humalog + rHuPH20 | Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG]) | AUC(BG) <70 mg/dL | 197.00 Milligrams per deciliter * minutes | Standard Deviation 480.75 |
| Humulin-R + rHuPH20 | Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG]) | AUC(BG) >160 mg/dL | 2509.65 Milligrams per deciliter * minutes | Standard Deviation 3332.36 |
| Humulin-R + rHuPH20 | Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG]) | AUC(BG) <70 mg/dL | 408.50 Milligrams per deciliter * minutes | Standard Deviation 602.29 |
| Humulin-R + rHuPH20 | Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG]) | AUC(BG) >140 mg/dL | 4905.92 Milligrams per deciliter * minutes | Standard Deviation 4829.71 |
Comparison: Participants with blood glucose (BG) \>160 milligrams per deciliter (mg/dL)p-value: 0.064Repeated Measures Analysis of Variance
Comparison: Participants with blood glucose (BG) \>160 milligrams per deciliter (mg/dL)p-value: 0.47Repeated Measures Analysis of Variance
Comparison: Participants with blood glucose (BG) \>160 milligrams per deciliter (mg/dL)p-value: 0.012Repeated Measures Analysis of Variance
Comparison: Participants with blood glucose (BG) \>140 milligrams per deciliter (mg/dL)p-value: 0.099Repeated Measures Analysis of Variance
Comparison: Participants with blood glucose (BG) \>140 milligrams per deciliter (mg/dL)p-value: 0.46Repeated Measures Analysis of Variance
Comparison: Participants with blood glucose (BG) \>140 milligrams per deciliter (mg/dL)p-value: 0.02Repeated Measures Analysis of Variance
Comparison: Participants with blood glucose (BG) \<70 milligrams per deciliter (mg/dL)p-value: 0.13Repeated Measures Analysis of Variance
Comparison: Participants with blood glucose (BG) \<70 milligrams per deciliter (mg/dL)p-value: 0.41Repeated Measures Analysis of Variance
Comparison: Participants with blood glucose (BG) \<70 milligrams per deciliter (mg/dL)p-value: 0.46Repeated Measures Analysis of Variance
Secondary
Maximum Serum Insulin Concentration (Cmax)
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 frame: Predose up to 480 minutes after study drug injection
Population: Participants who received at least one dose of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 with evaluable maximum serum insulin concentration (Cmax) data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Humalog Alone | Maximum Serum Insulin Concentration (Cmax) | 3329.49 Picomoles per liter (pm/L) | Standard Deviation 1090.02 |
| Humalog + rHuPH20 | Maximum Serum Insulin Concentration (Cmax) | 5661.92 Picomoles per liter (pm/L) | Standard Deviation 1307.75 |
| Humulin-R + rHuPH20 | Maximum Serum Insulin Concentration (Cmax) | 3011.56 Picomoles per liter (pm/L) | Standard Deviation 962.31 |
p-value: <0.0001Repeated Measures Analysis of Variance
p-value: 0.18Repeated Measures Analysis of Variance
p-value: <0.0001Repeated Measures Analysis of Variance
Secondary
Mean Residence Time From Time 0 to the End of Blood Sampling (MRT[Last])
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.
Time frame: Predose up to 480 minutes after study drug injection
Population: Participants who received at least 1 dose of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 with evaluable mean residence time from time 0 to the end of blood sampling (MRT\[last\]) data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Humalog Alone | Mean Residence Time From Time 0 to the End of Blood Sampling (MRT[Last]) | 148.79 Minutes (min) | Standard Deviation 22.46 |
| Humalog + rHuPH20 | Mean Residence Time From Time 0 to the End of Blood Sampling (MRT[Last]) | 108.23 Minutes (min) | Standard Deviation 20.56 |
| Humulin-R + rHuPH20 | Mean Residence Time From Time 0 to the End of Blood Sampling (MRT[Last]) | 150.24 Minutes (min) | Standard Deviation 27.32 |
p-value: <0.0001Repeated Measures Analysis of Variance
p-value: 0.77Repeated Measures Analysis of Variance
p-value: <0.0001Repeated Measures Analysis of Variance
Secondary
Minimum Postprandial Glucose (PPG)
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.
Time frame: Predose up to 480 minutes after study drug injection
Population: Participants who received at least 1 dose of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 with evaluable minimum postprandial glucose (PPG) data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Humalog Alone | Minimum Postprandial Glucose (PPG) | 76.38 Milligrams per deciliter (mg/dL) | Standard Deviation 22.58 |
| Humalog + rHuPH20 | Minimum Postprandial Glucose (PPG) | 88.52 Milligrams per deciliter (mg/dL) | Standard Deviation 27.37 |
| Humulin-R + rHuPH20 | Minimum Postprandial Glucose (PPG) | 75.62 Milligrams per deciliter (mg/dL) | Standard Deviation 20.15 |
p-value: 0.016Repeated Measures Analysis of Variance
p-value: 0.88Repeated Measures Analysis of Variance
p-value: 0.011Repeated Measures Analysis of Variance
Secondary
Percentage of Participants Without Hypoglycemia
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 frame: Predose up to 480 minutes after study drug injection
Population: Participants who received at least 1 dose of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Humalog Alone | Percentage of Participants Without Hypoglycemia | 81.0 Percentage of participants |
| Humalog + rHuPH20 | Percentage of Participants Without Hypoglycemia | 71.4 Percentage of participants |
| Humulin-R + rHuPH20 | Percentage of Participants Without Hypoglycemia | 71.4 Percentage of participants |
Secondary
Time to Early 50% Maximum Serum Insulin Concentration (Early[t50%])
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 frame: Predose up to 120 minutes after study drug injection
Population: Participants who received at least 1 dose of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 with evaluable time to early 50% maximum serum insulin concentration (early\[t50%\]) data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Humalog Alone | Time to Early 50% Maximum Serum Insulin Concentration (Early[t50%]) | 27.02 Minutes (min) | Standard Deviation 8.67 |
| Humalog + rHuPH20 | Time to Early 50% Maximum Serum Insulin Concentration (Early[t50%]) | 18.71 Minutes (min) | Standard Deviation 5.8 |
| Humulin-R + rHuPH20 | Time to Early 50% Maximum Serum Insulin Concentration (Early[t50%]) | 21.46 Minutes (min) | Standard Deviation 8.19 |
p-value: <0.0001Repeated Measures Analysis of Variance
p-value: 0.0016Repeated Measures Analysis of Variance
p-value: 0.1Repeated Measures Analysis of Variance
Secondary
Time to Late 50% Maximum Serum Insulin Concentration (Late[t50%])
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.
Time frame: Predose up to 480 minutes after study drug injection
Population: Participants who received at least 1 dose of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 with evaluable time to late 50% maximum serum insulin concentration (late\[t50%\]) data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Humalog Alone | Time to Late 50% Maximum Serum Insulin Concentration (Late[t50%]) | 206.86 Minutes (min) | Standard Deviation 41.66 |
| Humalog + rHuPH20 | Time to Late 50% Maximum Serum Insulin Concentration (Late[t50%]) | 123.93 Minutes (min) | Standard Deviation 44.59 |
| Humulin-R + rHuPH20 | Time to Late 50% Maximum Serum Insulin Concentration (Late[t50%]) | 220.33 Minutes (min) | Standard Deviation 51.98 |
p-value: <0.0001Repeated Measures Analysis of Variance
p-value: 0.3Repeated Measures Analysis of Variance
p-value: <0.0001Repeated Measures Analysis of Variance
Secondary
Time To Maximum Serum Insulin Concentration (Tmax)
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 frame: Predose up to 480 minutes after study drug injection
Population: Participants who received at least 1 dose of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 with evaluable time to maximum serum insulin concentration (Tmax) data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Humalog Alone | Time To Maximum Serum Insulin Concentration (Tmax) | 74.29 Minutes (min) | Standard Deviation 36.27 |
| Humalog + rHuPH20 | Time To Maximum Serum Insulin Concentration (Tmax) | 43.10 Minutes (min) | Standard Deviation 16.01 |
| Humulin-R + rHuPH20 | Time To Maximum Serum Insulin Concentration (Tmax) | 81.67 Minutes (min) | Standard Deviation 40.26 |
p-value: 0.0045Repeated Measures Analysis of Variance
p-value: 0.48Repeated Measures Analysis of Variance
p-value: 0.0006Repeated Measures Analysis of Variance
Secondary
Time to Percentage of Insulin Exposure (as Measured by Area Under the Curve [AUC])
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.
Time frame: Predose up to 480 minutes following after injection of study drug
Population: Participants who received at least 1 dose of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 with evaluable time to percentage of insulin exposure as measured by area under the curve (AUC) data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Humalog Alone | Time to Percentage of Insulin Exposure (as Measured by Area Under the Curve [AUC]) | Time to 10% Insulin Exposure | 46.05 Minutes (min) | Standard Deviation 8.98 |
| Humalog Alone | Time to Percentage of Insulin Exposure (as Measured by Area Under the Curve [AUC]) | Time to 50% Insulin Exposure | 135.73 Minutes (min) | Standard Deviation 21.18 |
| Humalog + rHuPH20 | Time to Percentage of Insulin Exposure (as Measured by Area Under the Curve [AUC]) | Time to 10% Insulin Exposure | 30.49 Minutes (min) | Standard Deviation 7.13 |
| Humalog + rHuPH20 | Time to Percentage of Insulin Exposure (as Measured by Area Under the Curve [AUC]) | Time to 50% Insulin Exposure | 94.49 Minutes (min) | Standard Deviation 20.06 |
| Humulin-R + rHuPH20 | Time to Percentage of Insulin Exposure (as Measured by Area Under the Curve [AUC]) | Time to 10% Insulin Exposure | 43.41 Minutes (min) | Standard Deviation 10.21 |
| Humulin-R + rHuPH20 | Time to Percentage of Insulin Exposure (as Measured by Area Under the Curve [AUC]) | Time to 50% Insulin Exposure | 137.52 Minutes (min) | Standard Deviation 27.35 |
Comparison: Analysis for 10% of exposure (area under the curve \[AUC\])p-value: <0.0001Repeated Measures Analysis of Variance
Comparison: Analysis for 50% of exposure (area under the curve \[AUC\])p-value: <0.0001Repeated Measures Analysis of Variance
Comparison: Analysis for 10% of exposure (area under the curve \[AUC\])p-value: <0.0001Repeated Measures Analysis of Variance
Comparison: Analysis for 10% of exposure (area under the curve \[AUC\])p-value: 0.18Repeated Measures Analysis of Variance
Comparison: Analysis for 50% of exposure (area under the curve \[AUC\])p-value: 0.72Repeated Measures Analysis of Variance
Comparison: Analysis for 50% of exposure (area under the curve \[AUC\])p-value: <0.0001Repeated Measures Analysis of Variance