Diabetes Type 1
Conditions
Keywords
insulin pump
Brief summary
The purpose of this study is to evaluate the compatibility and safety of LY900014 and insulin lispro with an external continuous subcutaneous insulin infusion system in adult participants with type 1 diabetes.
Interventions
DRUGLY900014
Administered by CSII
DRUGInsulin lispro
Administered by CSII
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
* Diagnosed with type 1 diabetes and have been using insulin continuously for at least 12 months. * Using an insulin pump with 'rapid-acting insulin' for at least 6 months and using the same rapid-acting insulin for at least the past 30 days. * Have experience using Continuous Glucose Monitoring (CGM) or Flash Glucose Monitoring (FGM) for at least 60 days during the past 12 months. * Have hemoglobin A1c values ≤8.5%, as determined by the central laboratory at screening. * Have a body mass index (BMI) of ≤35 kilograms per meter squared at screening. * Have been using the MiniMed 530G or 630G (US) or the MiniMed 640G (EU) insulin pump for at least the past 30 days.
Exclusion criteria
* Have had more than 1 emergency treatment for very low blood glucose in the last 6 months. * Have had more than 1 emergency treatment for poor glucose control (hyperglycemia or diabetic ketoacidosis) in the last 6 months. * Have significant insulin resistance defined as having received a total daily dose of insulin \>1.2 units per kilogram (U/kg) at screening, as determined by the average total daily insulin dose over the 3 days prior to screening divided by weight in kilograms based on investigator review of the participant's pump history. * Have significant lipohypertrophy, lipoatrophy, or scars within the subcutaneous tissue in areas of infusion or have a history of abscess at an infusion site within the last 90 days prior to screening. * Are receiving any oral or injectable medication intended for the treatment of diabetes mellitus other than rapid-acting analog insulin via CSII in the 90 days prior to screening. Occasional pen or syringe injection of insulin is allowed, for example, due to pump malfunction or unexplained hyperglycemia not responsive to pump correction bolus. * Taking certain diabetes medications that are not allowed for study participation. * Have major problems with heart, kidneys, liver, or have a blood disorder. * Have had or are now being treated for certain types of cancer that prevents study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Infusion Set Failures | 6 Weeks | Infusion set failure events are defined as premature infusion set changes, due to a pump occlusion alarm OR due to unexplained hyperglycemia with blood glucose (SMBG) \>250 milligrams per deciliter (mg/dL) (13.9 millimoles per liter \[mmol/L\]) that does not decrease within 1 hour following a correction bolus delivered via the pump during the 6 week treatment period. Aggregate rate was calculated for each participant as the total number of events while the participant is on study treatment divided by the days of exposure \[last dose date and time -first dose date and time -duration of pump or treatment interruption\] times 30. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Premature Infusion Set Changes | 6 Weeks | Rate of premature infusion set changes. |
| Time Interval Until Infusion Set Change | 6 Weeks | Time interval until infusion set change reflects the time interval in hours until infusion set change from first to last dose. MMRM model for post-baseline measures: Variable = Baseline + Period + Sequence + Strata(Region + Historical Use of SmartGuard/Threshold Suspend + HbA1c(\<=7.3%, \>7.3%)) + Treatment (Type III sum of squares). |
| Percentage of Participants With at Least 1 Event of Infusion Set Failure | 6 Weeks | Infusion set failures are defined as premature infusion set changes, due to a pump occlusion alarm OR due to unexplained hyperglycemia with blood glucose (SMBG) \>250mg/dL (13.9 mmol/L) that does not decrease within 1 hour following a correction bolus delivered via the pump. |
| Interstitial Glucose Reduction Rate From Hyperglycemia Following a Non-Meal-Related Correction Bolus Delivered Via the Pump | 6 Weeks | Interstitial glucose reduction rate (glucose reduction \[mg/dL\] per minute) within 4 hours following a non-meal-related correction bolus via the pump, from hyperglycemia (interstitial glucose \>180 mg/dL \[10 mmol/L\]) to recovery (interstitial glucose ≤180 mg/dL). |
| Number of Participants With Severe Hypoglycemic Events | 6 Weeks | Number of participants with severe hypoglycemic events. Severe hypoglycemia was defined as participants with an altered mental status and could not assist in their own care, may have been semiconscious or unconscious, or experienced coma with or without seizures, and the event required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Blood glucose measurements may not have been available during such an event, but neurological recovery attributable to the restoration of BG concentration to normal was considered sufficient evidence that the event was induced by a low BG concentration (BG ≤70 mg/dL \[3.9 mmol/L\]). |
| Ratio of Bolus/Total Insulin Dose | 6 Weeks | The bolus and total insulin doses for each visit was calculated as the mean of the doses for the last 3 days prior to the visit date that are entered in the eCRF. The bolus/total ratio was derived as the bolus dose divided by the total insulin dose at each visit. |
Countries
Spain, United States
Participant flow
Pre-assignment details
2-period crossover with no washout between periods and a 4 week safety follow-up.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 (LY900014/Insulin Lispro) 1. 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII) for six weeks
2. 100 U/mL insulin lispro (Humalog®) administered by CSII for six weeks with no washout between periods | 24 |
| Sequence 2 (Insulin Lispro/LY900014) 1. 100 U/mL insulin lispro (Humalog®) administered by CSII for 6 weeks
2. 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII) for six weeks with no washout between periods | 25 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Protocol Violation | 1 | 0 |
| Period 2 | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Sequence 1 (LY900014/Insulin Lispro) | Total | Sequence 2 (Insulin Lispro/LY900014) |
|---|---|---|---|
| Age, Continuous | 42.50 years STANDARD_DEVIATION 12.47 | 39.55 years STANDARD_DEVIATION 11.69 | 36.72 years STANDARD_DEVIATION 10.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 48 Participants | 25 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 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 | 23 Participants | 48 Participants | 25 Participants |
| Region of Enrollment Spain | 14 Participants | 28 Participants | 14 Participants |
| Region of Enrollment United States | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Female | 12 Participants | 26 Participants | 14 Participants |
| Sex: Female, Male Male | 12 Participants | 23 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 48 |
| other Total, other adverse events | 18 / 49 | 6 / 48 |
| serious Total, serious adverse events | 1 / 49 | 1 / 48 |
Outcome results
Primary
Rate of Infusion Set Failures
Infusion set failure events are defined as premature infusion set changes, due to a pump occlusion alarm OR due to unexplained hyperglycemia with blood glucose (SMBG) \>250 milligrams per deciliter (mg/dL) (13.9 millimoles per liter \[mmol/L\]) that does not decrease within 1 hour following a correction bolus delivered via the pump during the 6 week treatment period. Aggregate rate was calculated for each participant as the total number of events while the participant is on study treatment divided by the days of exposure \[last dose date and time -first dose date and time -duration of pump or treatment interruption\] times 30.
Time frame: 6 Weeks
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Lispro (Humalog®) | Rate of Infusion Set Failures | 0.05 events per 30 participant days |
| LY900014 | Rate of Infusion Set Failures | 0.03 events per 30 participant days |
p-value: 0.37595% CI: [0, 0]Wilcoxon signed-rank test
Secondary
Interstitial Glucose Reduction Rate From Hyperglycemia Following a Non-Meal-Related Correction Bolus Delivered Via the Pump
Interstitial glucose reduction rate (glucose reduction \[mg/dL\] per minute) within 4 hours following a non-meal-related correction bolus via the pump, from hyperglycemia (interstitial glucose \>180 mg/dL \[10 mmol/L\]) to recovery (interstitial glucose ≤180 mg/dL).
Time frame: 6 Weeks
Population: All randomized participants who received at least 1 dose of study drug and non-missing baseline value and at least one non-missing post-baseline value of the response.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro (Humalog®) | Interstitial Glucose Reduction Rate From Hyperglycemia Following a Non-Meal-Related Correction Bolus Delivered Via the Pump | 0.71 mg/dL/min | Standard Error 0.062 |
| LY900014 | Interstitial Glucose Reduction Rate From Hyperglycemia Following a Non-Meal-Related Correction Bolus Delivered Via the Pump | 0.82 mg/dL/min | Standard Error 0.063 |
p-value: 0.17795% CI: [-0.05, 0.27]Mixed Models Analysis
Secondary
Number of Participants With Severe Hypoglycemic Events
Number of participants with severe hypoglycemic events. Severe hypoglycemia was defined as participants with an altered mental status and could not assist in their own care, may have been semiconscious or unconscious, or experienced coma with or without seizures, and the event required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Blood glucose measurements may not have been available during such an event, but neurological recovery attributable to the restoration of BG concentration to normal was considered sufficient evidence that the event was induced by a low BG concentration (BG ≤70 mg/dL \[3.9 mmol/L\]).
Time frame: 6 Weeks
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Lispro (Humalog®) | Number of Participants With Severe Hypoglycemic Events | 1 participants |
| LY900014 | Number of Participants With Severe Hypoglycemic Events | 1 participants |
Secondary
Percentage of Participants With at Least 1 Event of Infusion Set Failure
Infusion set failures are defined as premature infusion set changes, due to a pump occlusion alarm OR due to unexplained hyperglycemia with blood glucose (SMBG) \>250mg/dL (13.9 mmol/L) that does not decrease within 1 hour following a correction bolus delivered via the pump.
Time frame: 6 Weeks
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Lispro (Humalog®) | Percentage of Participants With at Least 1 Event of Infusion Set Failure | 6.3 percentage of participants |
| LY900014 | Percentage of Participants With at Least 1 Event of Infusion Set Failure | 4.1 percentage of participants |
p-value: 0.468Prescott's Exact test
Secondary
Rate of Premature Infusion Set Changes
Rate of premature infusion set changes.
Time frame: 6 Weeks
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Lispro (Humalog®) | Rate of Premature Infusion Set Changes | 0.78 events per 30 participant days |
| LY900014 | Rate of Premature Infusion Set Changes | 1.13 events per 30 participant days |
p-value: 0.028Wilcoxon (Mann-Whitney)
Secondary
Ratio of Bolus/Total Insulin Dose
The bolus and total insulin doses for each visit was calculated as the mean of the doses for the last 3 days prior to the visit date that are entered in the eCRF. The bolus/total ratio was derived as the bolus dose divided by the total insulin dose at each visit.
Time frame: 6 Weeks
Population: All randomized participants who received at least 1 dose of study drug and non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro (Humalog®) | Ratio of Bolus/Total Insulin Dose | 46.6 percentage of total insulin dose | Standard Error 1.17 |
| LY900014 | Ratio of Bolus/Total Insulin Dose | 44.2 percentage of total insulin dose | Standard Error 1.17 |
p-value: 0.05795% CI: [-4.8, 0.1]Mixed Models Analysis
Secondary
Time Interval Until Infusion Set Change
Time interval until infusion set change reflects the time interval in hours until infusion set change from first to last dose. MMRM model for post-baseline measures: Variable = Baseline + Period + Sequence + Strata(Region + Historical Use of SmartGuard/Threshold Suspend + HbA1c(\<=7.3%, \>7.3%)) + Treatment (Type III sum of squares).
Time frame: 6 Weeks
Population: All randomized participants who received at least 1 dose of study drug and non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro (Humalog®) | Time Interval Until Infusion Set Change | 76.1 hours | Standard Error 1.52 |
| LY900014 | Time Interval Until Infusion Set Change | 74.3 hours | Standard Error 1.51 |
p-value: 0.30495% CI: [-5.3, 1.7]Mixed Models Analysis