Type1 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to compare the study drug LY900014 to insulin lispro (Humalog) when both are delivered by the Medtronic MiniMed 670G System in adults with type 1 diabetes (T1D). The study will consist of two treatment periods of 4 weeks.
Interventions
DRUGLY900014
Administered SC
DRUGInsulin Lispro
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have been diagnosed with type 1 diabetes and have been using insulin continuously for at least 12 months * Participants must be using an insulin pump with rapid-acting insulin for at least 6 months and the same rapid acting insulin for at least the past 30 days * Participants must have hemoglobin A1c (HbA1c) values ≥6.0% and ≤8.0% * Participants must have been using the MiniMed 670G insulin pump for at least the past 90 days * Participants must use their Guardian (3) sensor at least an average of 75% of the time and remain in Auto Mode an average of 70% of the time
Exclusion criteria
* Participants must not have had more than 1 emergency treatment for very low blood glucose or any hospitalizations for poor glucose control (very high blood sugar or diabetic ketoacidosis) in the last 6 months * Participants must not have significant abnormal accumulation of fat, loss of fat tissue, or scars just under the skin in areas of infusion or have a history of an infection at an infusion site within 90 days prior to screening * Participants must not have a total daily insulin dose \>100 units * Participants must not be receiving any oral or injectable medication intended for the treatment of diabetes other than rapid-acting analog insulin via CSII in the 30 days prior to screening * Participants must not have major problems with their heart, kidneys, liver, or have a blood disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Time With Sensor Glucose Values Between 70 and 180 Milligrams Per Deciliter (mg/dL) (24-Hour) | Week 2 through Week 4 | Least Square (LS) mean was determined by mixed-model repeated measures (MMRM) with baseline, period, sequence, strata (Hemoglobin A1c (HbA1c) \[\<=7.0%, \>7.0%\] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization \[\<=75%, \>75%\]), treatment (Type III sum of squares) as fixed factors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Sensor Glucose Value (24-Hour) | Week 2 through Week 4 | LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c \[\<=7.0%, \>7.0%\] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization \[\<=75%, \>75%\]), treatment (Type III sum of squares) as fixed factors. |
| Percentage of Time Spent in Auto Mode | Week 2 through Week 4 | LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c \[\<=7.0%, \>7.0%\] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization \[\<=75%, \>75%\]), treatment (Type III sum of squares) as fixed factors. |
| Percentage of Time With Sensor Glucose Values <54 mg/dL (24-Hour) | Week 2 through Week 4 | LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c \[\<=7.0%, \>7.0%\] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization \[\<=75%, \>75%\]), treatment (Type III sum of squares) as fixed factors. |
| Rate of Severe Hypoglycemic Events | Week 2 through Week 4 | Severe hypoglycemic is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience coma with or without seizures, and may require parenteral therapy. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group \*36525. No severe hypoglycemia was reported for this study. |
| Total Daily Insulin Dose | Week 2 through Week 4 | LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c \[\<=7.0%, \>7.0%\] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization \[\<=75%, \>75%\]), treatment (Type III sum of squares) as fixed factors. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 Participants received 100 units per milliliter (U/mL) of LY900014 or Humalog delivered via continuous subcutaneous insulin infusion (CSII) using the Medtronic MiniMed 670G insulin pump.
Period 1: LY900014 Period 2: Humalog | 20 |
| Sequence 2 Participants received 100 U/mL of LY900014 or Humalog delivered via CSII using the Medtronic MiniMed 670G insulin pump.
Period 1: Humalog Period 2: LY900014 | 22 |
| Total | 42 |
Baseline characteristics
| Characteristic | Sequence 1 | Total | Sequence 2 |
|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 14.9 | 47.8 years STANDARD_DEVIATION 13.8 | 48.1 years STANDARD_DEVIATION 13.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 42 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 40 Participants | 20 Participants |
| Region of Enrollment United States | 20 Participants | 42 Participants | 22 Participants |
| Sex: Female, Male Female | 12 Participants | 27 Participants | 15 Participants |
| Sex: Female, Male Male | 8 Participants | 15 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 42 |
| other Total, other adverse events | 4 / 42 | 1 / 42 |
| serious Total, serious adverse events | 0 / 42 | 0 / 42 |
Outcome results
Primary
Percentage of Time With Sensor Glucose Values Between 70 and 180 Milligrams Per Deciliter (mg/dL) (24-Hour)
Least Square (LS) mean was determined by mixed-model repeated measures (MMRM) with baseline, period, sequence, strata (Hemoglobin A1c (HbA1c) \[\<=7.0%, \>7.0%\] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization \[\<=75%, \>75%\]), treatment (Type III sum of squares) as fixed factors.
Time frame: Week 2 through Week 4
Population: All randomized participants who received at least one dose of study drug and had at least one post-baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | Percentage of Time With Sensor Glucose Values Between 70 and 180 Milligrams Per Deciliter (mg/dL) (24-Hour) | 76.98 Percentage of Time | Standard Error 0.857 |
| Insulin Lispro (Humalog) | Percentage of Time With Sensor Glucose Values Between 70 and 180 Milligrams Per Deciliter (mg/dL) (24-Hour) | 77.84 Percentage of Time | Standard Error 0.857 |
p-value: 0.33990% CI: [-2.35, 0.63]Mixed Models Analysis
Secondary
Mean Sensor Glucose Value (24-Hour)
LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c \[\<=7.0%, \>7.0%\] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization \[\<=75%, \>75%\]), treatment (Type III sum of squares) as fixed factors.
Time frame: Week 2 through Week 4
Population: All randomized participants who received at least one dose of study drug and had at least one post-baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | Mean Sensor Glucose Value (24-Hour) | 148.64 milligrams per deciliter (mg/dL) | Standard Error 1.193 |
| Insulin Lispro (Humalog) | Mean Sensor Glucose Value (24-Hour) | 145.64 milligrams per deciliter (mg/dL) | Standard Error 1.193 |
p-value: 0.01190% CI: [1.1, 4.9]Mixed Models Analysis
Secondary
Percentage of Time Spent in Auto Mode
LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c \[\<=7.0%, \>7.0%\] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization \[\<=75%, \>75%\]), treatment (Type III sum of squares) as fixed factors.
Time frame: Week 2 through Week 4
Population: All randomized participants who received at least one dose of study drug and had at least post-baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | Percentage of Time Spent in Auto Mode | 91.98 Percentage of Time | Standard Error 0.829 |
| Insulin Lispro (Humalog) | Percentage of Time Spent in Auto Mode | 91.42 Percentage of Time | Standard Error 0.838 |
p-value: 0.55790% CI: [-1.02, 2.14]Mixed Models Analysis
Secondary
Percentage of Time With Sensor Glucose Values <54 mg/dL (24-Hour)
LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c \[\<=7.0%, \>7.0%\] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization \[\<=75%, \>75%\]), treatment (Type III sum of squares) as fixed factors.
Time frame: Week 2 through Week 4
Population: All randomized participants who received at least one dose of study drug and had at least one post-baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | Percentage of Time With Sensor Glucose Values <54 mg/dL (24-Hour) | 0.34 Percentage of Time | Standard Error 0.067 |
| Insulin Lispro (Humalog) | Percentage of Time With Sensor Glucose Values <54 mg/dL (24-Hour) | 0.38 Percentage of Time | Standard Error 0.067 |
p-value: 0.54890% CI: [-0.15, 0.07]Mixed Models Analysis
Secondary
Rate of Severe Hypoglycemic Events
Severe hypoglycemic is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience coma with or without seizures, and may require parenteral therapy. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group \*36525. No severe hypoglycemia was reported for this study.
Time frame: Week 2 through Week 4
Population: All randomized participants with evaluable hypoglycemic data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | Rate of Severe Hypoglycemic Events | 0 Events/Participant/100 Years | Standard Deviation 0 |
| Insulin Lispro (Humalog) | Rate of Severe Hypoglycemic Events | 0 Events/Participant/100 Years | Standard Deviation 0 |
Secondary
Total Daily Insulin Dose
LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c \[\<=7.0%, \>7.0%\] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization \[\<=75%, \>75%\]), treatment (Type III sum of squares) as fixed factors.
Time frame: Week 2 through Week 4
Population: All randomized participants who received at least one dose of study drug and had at least one post-baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | Total Daily Insulin Dose | 42.59 Units (U)/day | Standard Error 1.023 |
| Insulin Lispro (Humalog) | Total Daily Insulin Dose | 42.10 Units (U)/day | Standard Error 1.023 |
p-value: 0.57790% CI: [-0.97, 1.94]Mixed Models Analysis