Diabetes Mellitus, Type 1
Conditions
Brief summary
This study will look into how a base dose of insulin peglispro and insulin glargine will affect the meal time dose and efficacy of insulin lispro in type 1 diabetics.
Interventions
Administered SC
DRUGInsulin Lispro
Administered SC
DRUGInsulin Glargine
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have a stable (within 0.5 percent (%) from last measure) glycated hemoglobin (HbA1c) \<9.0% * Have a stable (within 30%) basal insulin dose of 0.2 to 1.0 units per kilogram per day (U/kg/day) and a total daily insulin dose (basal + prandial/bolus) \<1.5 units per kilogram (U/kg) * Have C-peptide \<0.3 nanomoles per liter (nmol/L) * Are able and willing to eat the protocol specified standard breakfast and other meals as required
Exclusion criteria
* Have corrected QT interval (QTc) prolongation \>500 milliseconds (ms) or have any other abnormality in the 12 lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study * Have an abnormal blood pressure as determined by the investigator * Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (apart from Type 1 Diabetes Mellitus \[T1DM\]), hematological, or neurological disorders * Have fasting triglycerides (TGs) \>400 milligrams per deciliter (mg/dL) (4.52 micromoles per liter \[mmol/L\]) * Have used systemic corticosteroids within 4 weeks prior to randomization * Currently receive insulin pump or insulin degludec * Have poorly controlled diabetes or are known to have poor awareness of hypoglycemia * Have history of gastroparesis or gastrointestinal malabsorption * Require treatment with any drug other than insulin to treat diabetes * Have a previous history of proliferative retinopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | Day 30, 31, 32, 33, 34, pre-breakfast and10,20,30,40,50,60,90,120,150,180,210,240,270, 300 minutes (5 hours) post-breakfast | To quantitate the pharmacodynamic (PD) effect of a range of prandial insulin lispro doses after treatment with insulin peglispro (LY2605541) compared to insulin glargine during a meal tolerance test (MTT), with sequenced doses of insulin lispro ranging from 25% to 150% of each participant's normal dose. Data presented as hours times milligrams per deciliter (mg\*h/dL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value) | Day 35, last 60 minutes of euglycemic 2-step hyperinsulinemic clamp | Abbreviation for micro mole per kilogram per minute (µmol/kg/min). Both arms received insulin lispro in addition to their respective study drug. During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin of which the effect is largely on the liver and a high dose of insulin at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. Measurements for average glucose infusion rate are collected for both steps (low and high) of the clamp procedure. |
| Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Last Time (AUC [0 Tlast]) for Paracetamol | Day 29: Pre-breakfast, and 15, 30, 45, 60, 90, 120, 150,180,210,270, and 300 minutes (5 hours) post-breakfast | — |
| Pharmacokinetics (PK): Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro | Day 29: Pre-breakfast, and 15, 30, 45, 60, 90, 120, 150,180,210,270, and 300 minutes (5 hours) post-breakfast | Abbreviation for hours times picomol per liter (pmol\*h/L) |
| Pharmacodynamics (PD): Area Under the Concentration Zero Through 5 Hours (AUC 0-5h) for Triglycerides | Day 29, predose and 15, 30, 45, 60, 90, 120, 150,180,210,270, and 300 minutes (5 hours) post-breakfast | — |
| Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp | Day 35, insulin clearance during lispro infusion (dosing=infusion) | During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin (Low) of which the effect is largely on the liver and a high dose of insulin (high) at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. AUC is taking during infusion for this outcome measure. |
| Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Day 29:Upon waking, pre-breakfast, 1 hour (hr), 2 hr, 3 hr, 4 hr and 5 hr post breakfast | VAS was scored from 0 - 100 millimeters (mm) as a perception of appetite and satiety (Flint et al. 2000), 0 being not hungry at all or nothing at all and 100 being extremely hungry and extremely large amount. The questions are abbreviated in table from: How hungry do you feel right now? to Hunger and How much food do you think you could eat right now? to Food amount. Day 29 and cumulative insulin lispro doses of 25%, 50%, 75%, 100% and 150 % of normal insulin lispro dose included.Scores were averaged will be presented and calculated by a sum of the scores dividing by the total by the number of scores reported for timepoints and reported in millimeters. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All randomized participants who received at least 1 dose of study drug. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 1 | 1 |
| Period 1 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 44.2 years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Region of Enrollment Germany | 28 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 27 | 7 / 28 |
| serious Total, serious adverse events | 0 / 27 | 2 / 28 |
Outcome results
Primary
Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro
To quantitate the pharmacodynamic (PD) effect of a range of prandial insulin lispro doses after treatment with insulin peglispro (LY2605541) compared to insulin glargine during a meal tolerance test (MTT), with sequenced doses of insulin lispro ranging from 25% to 150% of each participant's normal dose. Data presented as hours times milligrams per deciliter (mg\*h/dL)
Time frame: Day 30, 31, 32, 33, 34, pre-breakfast and10,20,30,40,50,60,90,120,150,180,210,240,270, 300 minutes (5 hours) post-breakfast
Population: All participants who received at least 1 dose of study drug and had evaluable PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro (LY2605541) | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 100% Normal Dose | 270.46 mg*h/dL | Standard Deviation 201.73 |
| Insulin Peglispro (LY2605541) | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 25% Normal Dose | 677.84 mg*h/dL | Standard Deviation 146.48 |
| Insulin Peglispro (LY2605541) | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 150% Normal Dose | 174.38 mg*h/dL | Standard Deviation 182 |
| Insulin Peglispro (LY2605541) | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 50% Normal Dose | 572.96 mg*h/dL | Standard Deviation 149.76 |
| Insulin Peglispro (LY2605541) | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 75% Normal Dose | 393.28 mg*h/dL | Standard Deviation 175.68 |
| Insulin Glargine | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 50% Normal Dose | 506.22 mg*h/dL | Standard Deviation 188.54 |
| Insulin Glargine | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 75% Normal Dose | 369.08 mg*h/dL | Standard Deviation 169.08 |
| Insulin Glargine | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 100% Normal Dose | 307.81 mg*h/dL | Standard Deviation 204.27 |
| Insulin Glargine | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 150% Normal Dose | 123.97 mg*h/dL | Standard Deviation 118.82 |
| Insulin Glargine | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 25% Normal Dose | 716.52 mg*h/dL | Standard Deviation 179.89 |
Secondary
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
VAS was scored from 0 - 100 millimeters (mm) as a perception of appetite and satiety (Flint et al. 2000), 0 being not hungry at all or nothing at all and 100 being extremely hungry and extremely large amount. The questions are abbreviated in table from: How hungry do you feel right now? to Hunger and How much food do you think you could eat right now? to Food amount. Day 29 and cumulative insulin lispro doses of 25%, 50%, 75%, 100% and 150 % of normal insulin lispro dose included.Scores were averaged will be presented and calculated by a sum of the scores dividing by the total by the number of scores reported for timepoints and reported in millimeters.
Time frame: Day 29:Upon waking, pre-breakfast, 1 hour (hr), 2 hr, 3 hr, 4 hr and 5 hr post breakfast
Population: All participants who received at least 1 dose of study drug and had VAS score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Day 29: Hunger, waking | 27.1 millimeters (mm) | Standard Deviation 22.1 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 25%: Hunger, 5 hours post breakfast | 56.1 millimeters (mm) | Standard Deviation 30.7 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 25%: Food amount, waking | 30.8 millimeters (mm) | Standard Deviation 28.9 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 25%: Food amount, 5 hours post-breakfast | 56.5 millimeters (mm) | Standard Deviation 28 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 50%: Hunger, waking | 36.0 millimeters (mm) | Standard Deviation 26.2 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 50%: Food amount, 5 hours post-breakfast | 55.0 millimeters (mm) | Standard Deviation 24.8 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 75%: Hunger, 5 hours post breakfast | 55.5 millimeters (mm) | Standard Deviation 27.7 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 75%: Food amount, 5 hours post-breakfast | 57.0 millimeters (mm) | Standard Deviation 27.1 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 150%: Hunger, 5 hours post breakfast | 52.2 millimeters (mm) | Standard Deviation 27.7 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 150%: Food amount, waking | 34.3 millimeters (mm) | Standard Deviation 17.6 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Day 29: Hunger, 5 hours post breakfast | 53.8 millimeters (mm) | Standard Deviation 27.9 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Day 29: Food amount, waking | 32.5 millimeters (mm) | Standard Deviation 20.6 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Day 29: Food amount, 5 hours post-breakfast | 31.8 millimeters (mm) | Standard Deviation 20.1 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 25%: Hunger, waking | 27.5 millimeters (mm) | Standard Deviation 30.4 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 50%: Hunger, 5 hours post breakfast | 56.5 millimeters (mm) | Standard Deviation 26.7 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 50%: Food amount, waking | 37.1 millimeters (mm) | Standard Deviation 25.2 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 75%: Hunger, waking | 29.8 millimeters (mm) | Standard Deviation 25.4 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 75%: Food amount, waking | 32.6 millimeters (mm) | Standard Deviation 24.6 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 100%: Hunger, waking | 28.9 millimeters (mm) | Standard Deviation 22.9 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 100%: Hunger, 5 hours post breakfast | 55.0 millimeters (mm) | Standard Deviation 30.2 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 100%: Food amount, waking | 32.3 millimeters (mm) | Standard Deviation 22.9 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 100%: Food amount, 5 hours post-breakfast | 55.3 millimeters (mm) | Standard Deviation 29.1 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 150%: Hunger, waking | 31.4 millimeters (mm) | Standard Deviation 20.4 |
| Insulin Peglispro (LY2605541) | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 150%: Food amount, 5 hours post-breakfast | 52.7 millimeters (mm) | Standard Deviation 25.9 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 25%: Hunger, waking | 35.8 millimeters (mm) | Standard Deviation 28.5 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Day 29: Food amount, waking | 37.7 millimeters (mm) | Standard Deviation 22.8 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 25%: Food amount, waking | 36.4 millimeters (mm) | Standard Deviation 27.6 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 25%: Hunger, 5 hours post breakfast | 58.0 millimeters (mm) | Standard Deviation 26.2 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 25%: Food amount, 5 hours post-breakfast | 59.0 millimeters (mm) | Standard Deviation 24.9 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 50%: Hunger, waking | 28.2 millimeters (mm) | Standard Deviation 21.9 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 150%: Food amount, 5 hours post-breakfast | 58.3 millimeters (mm) | Standard Deviation 26.1 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 50%: Hunger, 5 hours post breakfast | 64.0 millimeters (mm) | Standard Deviation 25 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 50%: Food amount, 5 hours post-breakfast | 64.2 millimeters (mm) | Standard Deviation 23.5 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 150%: Hunger, 5 hours post breakfast | 58.6 millimeters (mm) | Standard Deviation 28.4 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 75%: Hunger, 5 hours post breakfast | 62.5 millimeters (mm) | Standard Deviation 25.3 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 50%: Food amount, waking | 31.7 millimeters (mm) | Standard Deviation 21.9 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 75%: Food amount, 5 hours post-breakfast | 62.2 millimeters (mm) | Standard Deviation 24 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 100%: Hunger, 5 hours post breakfast | 59.0 millimeters (mm) | Standard Deviation 26.9 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 150%: Hunger, waking | 28.5 millimeters (mm) | Standard Deviation 16.9 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 100%: Food amount, waking | 35.7 millimeters (mm) | Standard Deviation 23.7 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 75%: Hunger, waking | 30.9 millimeters (mm) | Standard Deviation 27.5 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Day 29: Hunger, waking | 32.1 millimeters (mm) | Standard Deviation 26.5 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 150%: Food amount, waking | 34.1 millimeters (mm) | Standard Deviation 17.1 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Day 29: Hunger, 5 hours post breakfast | 58.9 millimeters (mm) | Standard Deviation 24.6 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 75%: Food amount, waking | 31.4 millimeters (mm) | Standard Deviation 55.3 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 100%: Food amount, 5 hours post-breakfast | 58.6 millimeters (mm) | Standard Deviation 26.4 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Day 29: Food amount, 5 hours post-breakfast | 38.1 millimeters (mm) | Standard Deviation 21.8 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Overall 100%: Hunger, waking | 29.6 millimeters (mm) | Standard Deviation 24.3 |
Secondary
Pharmacodynamics (PD): Area Under the Concentration Zero Through 5 Hours (AUC 0-5h) for Triglycerides
Time frame: Day 29, predose and 15, 30, 45, 60, 90, 120, 150,180,210,270, and 300 minutes (5 hours) post-breakfast
Population: All participants who received at least 1 dose of study drug and had evaluable PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro (LY2605541) | Pharmacodynamics (PD): Area Under the Concentration Zero Through 5 Hours (AUC 0-5h) for Triglycerides | 6.85 ng*hr/mL | Standard Deviation 3.13 |
| Insulin Glargine | Pharmacodynamics (PD): Area Under the Concentration Zero Through 5 Hours (AUC 0-5h) for Triglycerides | 6.01 ng*hr/mL | Standard Deviation 2.22 |
Secondary
Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value)
Abbreviation for micro mole per kilogram per minute (µmol/kg/min). Both arms received insulin lispro in addition to their respective study drug. During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin of which the effect is largely on the liver and a high dose of insulin at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. Measurements for average glucose infusion rate are collected for both steps (low and high) of the clamp procedure.
Time frame: Day 35, last 60 minutes of euglycemic 2-step hyperinsulinemic clamp
Population: All participants who received at least 1 dose of study drug and had evaluable PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro (LY2605541) | Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value) | High Dose Insulin | 52.756 µmol/kg/min | Standard Deviation 11.862 |
| Insulin Peglispro (LY2605541) | Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value) | Low Dose Insulin | 13.908 µmol/kg/min | Standard Deviation 13.181 |
| Insulin Glargine | Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value) | High Dose Insulin | 56.321 µmol/kg/min | Standard Deviation 10.697 |
| Insulin Glargine | Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value) | Low Dose Insulin | 18.765 µmol/kg/min | Standard Deviation 8.293 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp
During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin (Low) of which the effect is largely on the liver and a high dose of insulin (high) at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. AUC is taking during infusion for this outcome measure.
Time frame: Day 35, insulin clearance during lispro infusion (dosing=infusion)
Population: All participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro (LY2605541) | Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp | Clamp Period 1-3 Hours | 243 pmol* hr/L | Standard Deviation 78.9 |
| Insulin Peglispro (LY2605541) | Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp | Clamp Period 4-6 Hours | 926 pmol* hr/L | Standard Deviation 335 |
| Insulin Glargine | Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp | Clamp Period 1-3 Hours | 222 pmol* hr/L | Standard Deviation 84.7 |
| Insulin Glargine | Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp | Clamp Period 4-6 Hours | 897 pmol* hr/L | Standard Deviation 333 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Last Time (AUC [0 Tlast]) for Paracetamol
Time frame: Day 29: Pre-breakfast, and 15, 30, 45, 60, 90, 120, 150,180,210,270, and 300 minutes (5 hours) post-breakfast
Population: All participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro (LY2605541) | Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Last Time (AUC [0 Tlast]) for Paracetamol | 33400 ng*hr/mL | Geometric Coefficient of Variation 19 |
| Insulin Glargine | Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Last Time (AUC [0 Tlast]) for Paracetamol | 33600 ng*hr/mL | Geometric Coefficient of Variation 22 |
Secondary
Pharmacokinetics (PK): Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro
Abbreviation for hours times picomol per liter (pmol\*h/L)
Time frame: Day 29: Pre-breakfast, and 15, 30, 45, 60, 90, 120, 150,180,210,270, and 300 minutes (5 hours) post-breakfast
Population: All participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro (LY2605541) | Pharmacokinetics (PK): Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro | 850 pmol*h/L | Geometric Coefficient of Variation 47 |
| Insulin Glargine | Pharmacokinetics (PK): Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro | 852 pmol*h/L | Geometric Coefficient of Variation 44 |