Diabetes Mellitus, Type 1
Conditions
Brief summary
This is a 6-sequence, 3-period (8 weeks each), 3-arm, 24-week crossover study. The purpose of this study is to provide information on the use of insulin lispro in insulin pumps (Continuous Subcutaneous Insulin Infusion \[CSII\]) compared to insulin aspart over 6 days of pump reservoir in-use. The study will also compare the in-use characteristics of insulin lispro infused at 6 days with insulin lispro infused at 2 days.
Interventions
DRUGInsulin lispro 2 day reservoir in-use
Insulin lispro 2 Day (L2D) administered by infusion pump for 8 week treatment period.
DRUGInsulin lispro 6 day reservoir in-use
Insulin lispro 6 Day (L6D) administered by infusion pump for 8 week treatment period.
DRUGInsulin aspart 6 day reservoir in-use
Insulin aspart 6 Day (A6D) administered by infusion pump for 8 week treatment period.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with type 1 diabetes (World Health Organization criteria) for at least 24 months. * Treated with continuous subcutaneous insulin infusion therapy for the previous 6 months. * Mean total daily insulin dose for 3 days prior to screening equal to or less than 46 units/day using a 300-unit reservoir or less than or equal to 26 units/day using a 180 unit reservoir. * Baseline body mass index (BMI) less than or equal to 35.0 kg/m\^2. * Baseline glycosylated hemoglobin (HbA1c) 5% to 9%.
Exclusion criteria
* Impaired renal function (serum creatinine greater than or equal to 2.0 milligrams per deciliter \[mg/dL\]). * Legal blindness. * Have had any episode of hypoglycemic coma, seizures, or disorientation in the 12 months prior to screening. * Have had hypoglycemia unawareness (routinely asymptomatic at blood glucose (BG) less than 45 mg/dL) in the 12 months prior to screening. * Have had any emergency room visits or hospitalizations due to poor glucose control in the 12 months prior to screening. * Have had a pump-related infusion site abscess in the 12 months prior to screening. * Have had multiple, clinically significant occlusions as judged by the investigator. * Have had any infection with staphylococcus aureus in the past 5 years. * Have one of the following concomitant diseases: presence of clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal disease, or any other serious disease considered by the investigator to be exclusionary. * Patients with malignancy other than basal cell or squamous cell skin cancer who have not yet been treated, are currently being treated, or who were diagnosed less than 5 years ago. * Have had a blood transfusion or severe blood loss within 3 months prior to screening, or have known hemoglobinopathy, hemolytic anemia or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with HbA1c methodology. * Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intra-articular, intraocular and inhaled prescriptions), or have received such therapy within the 4 weeks immediately preceding screening. * Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night), in the investigator's opinion. * Have known hypersensitivity or allergy to any of the study insulins or their excipients. * Are breastfeeding or pregnant, or intend to become pregnant during the course of the study, or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable. * Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. * Have previously completed or withdrawn from this study after having signed the informed consent document (ICD). * Are unwilling or unable to comply with the use of a data collection device to directly record data from the patient.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean of Last Five 7-point Self Monitored Blood Glucose (SMBG) Taken on Day 6 for Insulin Lispro 6D and Day 2 for Insulin Lispro 2D and Day 6 for Insulin Aspart 6D Pump Reservoir In-use | 8 weeks of each treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Daily Insulin Dose (Total, Basal, and Bolus) | 8 weeks for each treatment | — |
| Change From Baseline to 8 Weeks Endpoint for Each Treatment in Hemoglobin A1c (HbA1c) Values | Baseline, 8 weeks for each treatment | — |
| Number of Participants Who Achieve or Maintain an HbA1c Less Than or Equal to 6.5% and Less Than 7% | 8 weeks for each treatment | — |
| Percentage of Participants With Hyperglycemia | 8 weeks for each treatment | Hyperglycemia was defined as an event with (1) a measured blood glucose concentration \>250 milligrams per deciliter (mg/dL) (13.9 mmol/L) and ≥3 hours after eating, or (2) a measured blood glucose concentration \>300 mg/dL (16.7 mmol/L) and \<3 hours after eating. |
| Hyperglycemic Episode Rate Per 30 Days | 8 weeks for each treatment | Hyperglycemia was defined as an episode with (1) a measured blood glucose concentration \>250 milligrams per deciliter (mg/dL) (13.9 mmol/L) and ≥3 hours after eating, or (2) a measured blood glucose concentration \>300 mg/dL (16.7 mmol/L) and \<3 hours after eating. Rate is presented as the number of hyperglycemic episodes adjusted for 30 days. |
| Mean SMBG | 8 weeks for each treatment | Mean SMBG for combined periods; all reported SMBG values on days 1-6 for Insulin Lispro 6 Day and Insulin Aspart 6 Day, and days 1-2 for Insulin Lispro 2 Day. |
| Pump Complication Rate Per 30 Days | 8 weeks for each treatment | Overall Pump Complications were any combination of: tubing clogged, kinked, disconnected, pulled out, blood in tubing; too much heat, too much cold, empty reservoir, low battery, occlusion alarm, no delivery alarm; at site - skin abscess, excessive redness, swelling (not nodule), bleeding, bruising; reservoir change (infusion set change reason only); and other. When either a reservoir change or an infusion set change was reported, participants were questioned whether change was early (prior to 6 days for L6D or A6D, or prior to 2 days for L2D). If 'yes', then recorded as premature change. |
| Percentage of Participants With Hypoglycemia | 8 weeks for each treatment | Hypoglycemia was defined as an event which was associated with 1. reported signs and symptoms of hypoglycemia, and/or 2. a documented blood glucose (BG) concentration of ≤ 70 mg/dL (3.9 mmol/L). |
| Hypoglycemia Episode Rate Per 30 Days | 8 weeks for each treatment | Hypoglycemia was defined as an event which was associated with 1. reported signs and symptoms of hypoglycemia, and/or 2. a documented blood glucose (BG) concentration of ≤ 70 mg/dL (3.9 mmol/L). Rate is presented as the number of hypoglycemic episodes adjusted for 30 days. |
| Change From Baseline to 8 Weeks Endpoint for Each Treatment in Weight | Baseline, 8 weeks for each treatment | — |
| Change From Baseline to 8 Weeks Endpoint for Each Treatment in Blood Pressure | Baseline, 8 weeks for each treatment | — |
| Percentage of Participants With Pump Complications | 8 weeks for each treatment | Overall Pump Complications were any combination of: tubing clogged, kinked, disconnected, pulled out, blood in tubing; too much heat, too much cold, empty reservoir, low battery, occlusion alarm, no delivery alarm; at site - skin abscess, excessive redness, swelling (not nodule), bleeding, bruising; reservoir change (infusion set change reason only); and other. When either a reservoir change or an infusion set change was reported, participants were questioned whether change was early (prior to 6 days for L6D or A6D, or prior to 2 days for L2D). If 'yes', then recorded as premature change. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence A (L2D/L6D/A6D) Participants received Insulin Lispro 2D (2 Days), Insulin Lispro 6D and Insulin Aspart 6D as per below dosing schedule Period 1: Lispro 2D, Period 2: Lispro 6D and Period 3: Insulin Aspart 6D. | 22 |
| Sequence B (L2D/A6D/L6D) Participants received Insulin Lispro 2D, Insulin Lispro 6D and Insulin Aspart 6D as per below dosing schedule Period 1:
Insulin Lispro 2D, Period 2: Insulin Aspart 6D and Period 3: Insulin Lispro 6D. | 22 |
| Sequence C (L6D/L2D/A6D) Participants received Insulin Lispro 2D, Insulin Lispro 6D and Insulin Aspart 6D as per below dosing schedule Period 1: Insulin Lispro 6D, Period 2: Insulin Lispro 2D and Period 3: Insulin Aspart 6D. | 22 |
| Sequence D (L6D/A6D/L2D) Participants received Insulin Lispro 2D, Insulin Lispro 6D and Insulin Aspart 6D as per below dosing schedule Period 1:
Insulin Lispro 6D, Period 2: Insulin Aspart 6D and Period 3: Insulin Lispro 2D. | 22 |
| Sequence E (A6D/L2D/L6D) Participants received Insulin Lispro 2D, Insulin Lispro 6D and Insulin Aspart 6D as per below dosing schedule Period 1: Insulin Aspart 6D, Period 2: Insulin Lispro 2D and Period 3: Insulin Lispro 6D. | 22 |
| Sequence F (A6D/L6D/L2D) Participants received Insulin Lispro 2D, Insulin Lispro 6D and Insulin Aspart 6D as per below dosing schedule Period 1: Insulin Aspart 6D, Period 2: Insulin Lispro 6D and Period 3: Insulin Lispro 2D. | 22 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Study Period 1 | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 |
| Study Period 1 | Lost to Follow-up | 0 | 0 | 1 | 1 | 0 | 0 |
| Study Period 1 | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 2 |
| Study Period 1 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 2 | 0 |
| Study Period 2 | Entry Criteria Not Met | 0 | 1 | 0 | 0 | 0 | 0 |
| Study Period 2 | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 |
| Study Period 2 | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 |
| Study Period 2 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 1 |
| Study Period 3 | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Study Period 3 | Withdrawal by Subject | 1 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Sequence A (L2D/L6D/A6D) | Total | Sequence F (A6D/L6D/L2D) | Sequence E (A6D/L2D/L6D) | Sequence D (L6D/A6D/L2D) | Sequence C (L6D/L2D/A6D) | Sequence B (L2D/A6D/L6D) |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 42.28 years STANDARD_DEVIATION 19.62 | 41.37 years STANDARD_DEVIATION 16.68 | 38.34 years STANDARD_DEVIATION 14.93 | 41.15 years STANDARD_DEVIATION 14.22 | 47.23 years STANDARD_DEVIATION 18.78 | 42.63 years STANDARD_DEVIATION 17.39 | 36.61 years STANDARD_DEVIATION 14.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 12 Participants | 3 Participants | 3 Participants | 0 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 120 Participants | 19 Participants | 19 Participants | 22 Participants | 21 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 129 Participants | 21 Participants | 22 Participants | 21 Participants | 22 Participants | 21 Participants |
| Region of Enrollment United States | 22 Participants | 132 Participants | 22 Participants | 22 Participants | 22 Participants | 22 Participants | 22 Participants |
| Sex: Female, Male Female | 15 Participants | 96 Participants | 18 Participants | 18 Participants | 14 Participants | 15 Participants | 16 Participants |
| Sex: Female, Male Male | 7 Participants | 36 Participants | 4 Participants | 4 Participants | 8 Participants | 7 Participants | 6 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 | 71 / 122 | 68 / 127 | 71 / 124 |
| serious Total, serious adverse events | 3 / 122 | 8 / 127 | 10 / 124 |
Outcome results
Primary
Mean of Last Five 7-point Self Monitored Blood Glucose (SMBG) Taken on Day 6 for Insulin Lispro 6D and Day 2 for Insulin Lispro 2D and Day 6 for Insulin Aspart 6D Pump Reservoir In-use
Time frame: 8 weeks of each treatment
Population: All randomized participants who completed at least one post-randomization visit. Those included in the Primary analysis had to have at least one reservoir in-use cycle with an SMBG measurement on Day 6 during the pre-specified collection period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro 2 Day | Mean of Last Five 7-point Self Monitored Blood Glucose (SMBG) Taken on Day 6 for Insulin Lispro 6D and Day 2 for Insulin Lispro 2D and Day 6 for Insulin Aspart 6D Pump Reservoir In-use | 9.03 millimoles per liter (mmol/L) | Standard Deviation 2.17 |
| Insulin Lispro 6 Day | Mean of Last Five 7-point Self Monitored Blood Glucose (SMBG) Taken on Day 6 for Insulin Lispro 6D and Day 2 for Insulin Lispro 2D and Day 6 for Insulin Aspart 6D Pump Reservoir In-use | 9.33 millimoles per liter (mmol/L) | Standard Deviation 2.31 |
| Insulin Aspart 6 Day | Mean of Last Five 7-point Self Monitored Blood Glucose (SMBG) Taken on Day 6 for Insulin Lispro 6D and Day 2 for Insulin Lispro 2D and Day 6 for Insulin Aspart 6D Pump Reservoir In-use | 8.72 millimoles per liter (mmol/L) | Standard Deviation 1.82 |
Comparison: This was the primary gated analysis.95% CI: [0.2, 0.76]
Secondary
Change From Baseline to 8 Weeks Endpoint for Each Treatment in Blood Pressure
Time frame: Baseline, 8 weeks for each treatment
Population: All randomized participants who received at least one dose of study drug and had both baseline and post-baseline blood pressure measurements for the respective treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro 2 Day | Change From Baseline to 8 Weeks Endpoint for Each Treatment in Blood Pressure | Systolic Blood Pressure (SBP) | 0.80 mmHg | Standard Deviation 12.82 |
| Insulin Lispro 2 Day | Change From Baseline to 8 Weeks Endpoint for Each Treatment in Blood Pressure | Diastolic Blood Pressure (DBP) | -0.14 mmHg | Standard Deviation 8.24 |
| Insulin Lispro 6 Day | Change From Baseline to 8 Weeks Endpoint for Each Treatment in Blood Pressure | Systolic Blood Pressure (SBP) | 0.80 mmHg | Standard Deviation 12.52 |
| Insulin Lispro 6 Day | Change From Baseline to 8 Weeks Endpoint for Each Treatment in Blood Pressure | Diastolic Blood Pressure (DBP) | 1.37 mmHg | Standard Deviation 7.62 |
| Insulin Aspart 6 Day | Change From Baseline to 8 Weeks Endpoint for Each Treatment in Blood Pressure | Systolic Blood Pressure (SBP) | -1.07 mmHg | Standard Deviation 12.06 |
| Insulin Aspart 6 Day | Change From Baseline to 8 Weeks Endpoint for Each Treatment in Blood Pressure | Diastolic Blood Pressure (DBP) | -0.33 mmHg | Standard Deviation 7.88 |
p-value: 0.056Crossover Model
p-value: 0.805Crossover Model
p-value: 0.02Crossover Model
p-value: 0.051Crossover Model
Secondary
Change From Baseline to 8 Weeks Endpoint for Each Treatment in Hemoglobin A1c (HbA1c) Values
Time frame: Baseline, 8 weeks for each treatment
Population: All randomized participants who completed at least one post-randomization visit, and had a baseline and a post-randomization HbA1c measurement for the respective treatment period. Last Observation Carried Forward (LOCF) method was utilized in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro 2 Day | Change From Baseline to 8 Weeks Endpoint for Each Treatment in Hemoglobin A1c (HbA1c) Values | -0.04 percentage of glycosylated hemoglobin | Standard Deviation 0.59 |
| Insulin Lispro 6 Day | Change From Baseline to 8 Weeks Endpoint for Each Treatment in Hemoglobin A1c (HbA1c) Values | 0.06 percentage of glycosylated hemoglobin | Standard Deviation 0.56 |
| Insulin Aspart 6 Day | Change From Baseline to 8 Weeks Endpoint for Each Treatment in Hemoglobin A1c (HbA1c) Values | 0.00 percentage of glycosylated hemoglobin | Standard Deviation 0.53 |
95% CI: [-0.02, 0.14]
95% CI: [0.01, 0.18]
Secondary
Change From Baseline to 8 Weeks Endpoint for Each Treatment in Weight
Time frame: Baseline, 8 weeks for each treatment
Population: All randomized participants who received at least one dose of study drug and had both baseline and post-baseline weight measurements for the respective treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro 2 Day | Change From Baseline to 8 Weeks Endpoint for Each Treatment in Weight | 0.44 kilograms (kg) | Standard Deviation 2.13 |
| Insulin Lispro 6 Day | Change From Baseline to 8 Weeks Endpoint for Each Treatment in Weight | 0.34 kilograms (kg) | Standard Deviation 2.04 |
| Insulin Aspart 6 Day | Change From Baseline to 8 Weeks Endpoint for Each Treatment in Weight | 0.65 kilograms (kg) | Standard Deviation 2.13 |
p-value: 0.06Crossover Model
p-value: 0.486Crossover Model
Secondary
Hyperglycemic Episode Rate Per 30 Days
Hyperglycemia was defined as an episode with (1) a measured blood glucose concentration \>250 milligrams per deciliter (mg/dL) (13.9 mmol/L) and ≥3 hours after eating, or (2) a measured blood glucose concentration \>300 mg/dL (16.7 mmol/L) and \<3 hours after eating. Rate is presented as the number of hyperglycemic episodes adjusted for 30 days.
Time frame: 8 weeks for each treatment
Population: All randomized participants who received at least one dose of study drug. Participants included in hyperglycemia analyses are only those for whom data existed regarding hyperglycemia.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro 2 Day | Hyperglycemic Episode Rate Per 30 Days | 15.91 hyperglycemic episodes per 30 days | Standard Deviation 12.78 |
| Insulin Lispro 6 Day | Hyperglycemic Episode Rate Per 30 Days | 16.91 hyperglycemic episodes per 30 days | Standard Deviation 13.98 |
| Insulin Aspart 6 Day | Hyperglycemic Episode Rate Per 30 Days | 15.76 hyperglycemic episodes per 30 days | Standard Deviation 12.04 |
p-value: 0.164Negative Binomial Test
p-value: 0.185Negative Binomial Test
Secondary
Hypoglycemia Episode Rate Per 30 Days
Hypoglycemia was defined as an event which was associated with 1. reported signs and symptoms of hypoglycemia, and/or 2. a documented blood glucose (BG) concentration of ≤ 70 mg/dL (3.9 mmol/L). Rate is presented as the number of hypoglycemic episodes adjusted for 30 days.
Time frame: 8 weeks for each treatment
Population: All randomized participants who received at least one dose of study drug. Participants included in hypoglycemia analyses are only those for whom data existed regarding hypoglycemia.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro 2 Day | Hypoglycemia Episode Rate Per 30 Days | 17.90 hypoglycemic episodes per 30 days | Standard Deviation 11.13 |
| Insulin Lispro 6 Day | Hypoglycemia Episode Rate Per 30 Days | 15.66 hypoglycemic episodes per 30 days | Standard Deviation 12.29 |
| Insulin Aspart 6 Day | Hypoglycemia Episode Rate Per 30 Days | 17.52 hypoglycemic episodes per 30 days | Standard Deviation 11.76 |
p-value: 0.006Negative Binomial Test
p-value: 0.002Negative Binomial Test
Secondary
Mean Daily Insulin Dose (Total, Basal, and Bolus)
Time frame: 8 weeks for each treatment
Population: All randomized participants who completed at least one post-randomization visit. Participants included in insulin analyses are only those for whom data existed regarding insulin dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro 2 Day | Mean Daily Insulin Dose (Total, Basal, and Bolus) | Daily Basal Insulin | 18.62 Units (U) of insulin | Standard Deviation 9.32 |
| Insulin Lispro 2 Day | Mean Daily Insulin Dose (Total, Basal, and Bolus) | Daily Bolus Insulin | 14.33 Units (U) of insulin | Standard Deviation 5.88 |
| Insulin Lispro 2 Day | Mean Daily Insulin Dose (Total, Basal, and Bolus) | Daily Total Insulin | 32.36 Units (U) of insulin | Standard Deviation 10.28 |
| Insulin Lispro 6 Day | Mean Daily Insulin Dose (Total, Basal, and Bolus) | Daily Basal Insulin | 18.77 Units (U) of insulin | Standard Deviation 8.89 |
| Insulin Lispro 6 Day | Mean Daily Insulin Dose (Total, Basal, and Bolus) | Daily Bolus Insulin | 14.51 Units (U) of insulin | Standard Deviation 6.33 |
| Insulin Lispro 6 Day | Mean Daily Insulin Dose (Total, Basal, and Bolus) | Daily Total Insulin | 32.37 Units (U) of insulin | Standard Deviation 10.12 |
| Insulin Aspart 6 Day | Mean Daily Insulin Dose (Total, Basal, and Bolus) | Daily Bolus Insulin | 14.44 Units (U) of insulin | Standard Deviation 6.11 |
| Insulin Aspart 6 Day | Mean Daily Insulin Dose (Total, Basal, and Bolus) | Daily Total Insulin | 31.99 Units (U) of insulin | Standard Deviation 10.15 |
| Insulin Aspart 6 Day | Mean Daily Insulin Dose (Total, Basal, and Bolus) | Daily Basal Insulin | 18.34 Units (U) of insulin | Standard Deviation 8.72 |
95% CI: [-0.29, 0.51]
95% CI: [-0.41, 0.73]
95% CI: [-0.18, 0.24]
95% CI: [-0.56, 0.27]
95% CI: [-0.48, 0.6]
95% CI: [-0.85, 0.65]
Secondary
Mean SMBG
Mean SMBG for combined periods; all reported SMBG values on days 1-6 for Insulin Lispro 6 Day and Insulin Aspart 6 Day, and days 1-2 for Insulin Lispro 2 Day.
Time frame: 8 weeks for each treatment
Population: All randomized participants who completed at least one post-randomization visit and one SMBG measurement on Day 2 for insulin lispro 2 day or Day 6 for the respective treatment arm: insulin lispro 6 day and insulin aspart 6 day.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro 2 Day | Mean SMBG | 8.79 mmol/L | Standard Deviation 2.73 |
| Insulin Lispro 6 Day | Mean SMBG | 9.01 mmol/L | Standard Deviation 2.87 |
| Insulin Aspart 6 Day | Mean SMBG | 8.83 mmol/L | Standard Deviation 2.71 |
95% CI: [-0.07, 0.52]
95% CI: [-0.05, 0.56]
Secondary
Number of Participants Who Achieve or Maintain an HbA1c Less Than or Equal to 6.5% and Less Than 7%
Time frame: 8 weeks for each treatment
Population: All randomized participants who completed a post-randomization visit and had an HbA1c measurement for the respective treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Lispro 2 Day | Number of Participants Who Achieve or Maintain an HbA1c Less Than or Equal to 6.5% and Less Than 7% | HbA1c ≤6.5% | 21 participants |
| Insulin Lispro 2 Day | Number of Participants Who Achieve or Maintain an HbA1c Less Than or Equal to 6.5% and Less Than 7% | HbA1c <7% | 40 participants |
| Insulin Lispro 6 Day | Number of Participants Who Achieve or Maintain an HbA1c Less Than or Equal to 6.5% and Less Than 7% | HbA1c ≤6.5% | 16 participants |
| Insulin Lispro 6 Day | Number of Participants Who Achieve or Maintain an HbA1c Less Than or Equal to 6.5% and Less Than 7% | HbA1c <7% | 38 participants |
| Insulin Aspart 6 Day | Number of Participants Who Achieve or Maintain an HbA1c Less Than or Equal to 6.5% and Less Than 7% | HbA1c ≤6.5% | 18 participants |
| Insulin Aspart 6 Day | Number of Participants Who Achieve or Maintain an HbA1c Less Than or Equal to 6.5% and Less Than 7% | HbA1c <7% | 44 participants |
95% CI: [0.5, 1.75]
95% CI: [0.29, 1.67]
95% CI: [0.56, 1.41]
95% CI: [0.66, 1.64]
Secondary
Percentage of Participants With Hyperglycemia
Hyperglycemia was defined as an event with (1) a measured blood glucose concentration \>250 milligrams per deciliter (mg/dL) (13.9 mmol/L) and ≥3 hours after eating, or (2) a measured blood glucose concentration \>300 mg/dL (16.7 mmol/L) and \<3 hours after eating.
Time frame: 8 weeks for each treatment
Population: All randomized participants who received at least one dose of study drug. Participants included in hyperglycemia analyses are only those for whom data existed regarding hyperglycemia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Lispro 2 Day | Percentage of Participants With Hyperglycemia | 99.2 percentage of participants |
| Insulin Lispro 6 Day | Percentage of Participants With Hyperglycemia | 98.4 percentage of participants |
| Insulin Aspart 6 Day | Percentage of Participants With Hyperglycemia | 98.4 percentage of participants |
p-value: 1Gart's Test
Secondary
Percentage of Participants With Hypoglycemia
Hypoglycemia was defined as an event which was associated with 1. reported signs and symptoms of hypoglycemia, and/or 2. a documented blood glucose (BG) concentration of ≤ 70 mg/dL (3.9 mmol/L).
Time frame: 8 weeks for each treatment
Population: All randomized participants who received at least one dose of study drug. Participants included in hypoglycemia analyses are only those for whom data existed regarding hypoglycemia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Lispro 2 Day | Percentage of Participants With Hypoglycemia | 100.0 percentage of participants |
| Insulin Lispro 6 Day | Percentage of Participants With Hypoglycemia | 100.0 percentage of participants |
| Insulin Aspart 6 Day | Percentage of Participants With Hypoglycemia | 99.2 percentage of participants |
Secondary
Percentage of Participants With Pump Complications
Overall Pump Complications were any combination of: tubing clogged, kinked, disconnected, pulled out, blood in tubing; too much heat, too much cold, empty reservoir, low battery, occlusion alarm, no delivery alarm; at site - skin abscess, excessive redness, swelling (not nodule), bleeding, bruising; reservoir change (infusion set change reason only); and other. When either a reservoir change or an infusion set change was reported, participants were questioned whether change was early (prior to 6 days for L6D or A6D, or prior to 2 days for L2D). If 'yes', then recorded as premature change.
Time frame: 8 weeks for each treatment
Population: All randomized participants who completed at least one post-randomization visit. Participants included in pump complication analyses are only those for whom data existed regarding pump complications.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Lispro 2 Day | Percentage of Participants With Pump Complications | Pump Complication: Premature Reservoir Change | 23.8 percentage of participants |
| Insulin Lispro 2 Day | Percentage of Participants With Pump Complications | Pump Complication: Premature Infusion Set Change | 42.6 percentage of participants |
| Insulin Lispro 6 Day | Percentage of Participants With Pump Complications | Pump Complication: Premature Reservoir Change | 38.6 percentage of participants |
| Insulin Lispro 6 Day | Percentage of Participants With Pump Complications | Pump Complication: Premature Infusion Set Change | 59.1 percentage of participants |
| Insulin Aspart 6 Day | Percentage of Participants With Pump Complications | Pump Complication: Premature Reservoir Change | 36.3 percentage of participants |
| Insulin Aspart 6 Day | Percentage of Participants With Pump Complications | Pump Complication: Premature Infusion Set Change | 56.5 percentage of participants |
p-value: 0.736Gart's Test
p-value: 0.006Gart's Test
p-value: 1Gart's Test
p-value: 0.017Gart's Test
Secondary
Pump Complication Rate Per 30 Days
Overall Pump Complications were any combination of: tubing clogged, kinked, disconnected, pulled out, blood in tubing; too much heat, too much cold, empty reservoir, low battery, occlusion alarm, no delivery alarm; at site - skin abscess, excessive redness, swelling (not nodule), bleeding, bruising; reservoir change (infusion set change reason only); and other. When either a reservoir change or an infusion set change was reported, participants were questioned whether change was early (prior to 6 days for L6D or A6D, or prior to 2 days for L2D). If 'yes', then recorded as premature change.
Time frame: 8 weeks for each treatment
Population: All randomized participants who completed at least one post-randomization visit. Participants included in pump complication analyses are only those for whom data existed regarding pump complications.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro 2 Day | Pump Complication Rate Per 30 Days | Pump Complication: Premature Reservoir Change | 0.16 pump complications per 30 days | Standard Deviation 0.34 |
| Insulin Lispro 2 Day | Pump Complication Rate Per 30 Days | Pump Complication: Premature Infusion Set Change | 0.44 pump complications per 30 days | Standard Deviation 0.65 |
| Insulin Lispro 6 Day | Pump Complication Rate Per 30 Days | Pump Complication: Premature Reservoir Change | 0.40 pump complications per 30 days | Standard Deviation 0.76 |
| Insulin Lispro 6 Day | Pump Complication Rate Per 30 Days | Pump Complication: Premature Infusion Set Change | 0.84 pump complications per 30 days | Standard Deviation 1.18 |
| Insulin Aspart 6 Day | Pump Complication Rate Per 30 Days | Pump Complication: Premature Reservoir Change | 0.51 pump complications per 30 days | Standard Deviation 1.05 |
| Insulin Aspart 6 Day | Pump Complication Rate Per 30 Days | Pump Complication: Premature Infusion Set Change | 0.94 pump complications per 30 days | Standard Deviation 1.35 |
p-value: <0.001Negative Binomial Test
p-value: 0.471Negative Binomial Test
p-value: 0.737Negative Binomial Test
p-value: <0.001Negative Binomial Test