Diabetes Mellitus, Type 1
Conditions
Brief summary
The purpose of this study is to test the hypothesis that the HumaPen Memoir with memory function, when used over 24 weeks for prandial insulin injections achieves superior glycemic control, when compared to the conventional HumaPen Luxura without memory function.
Interventions
DRUGInsulin Lispro
subcutaneously, daily (as determined by patient's blood glucose), for 24 weeks
DRUGHuminsulin Regular
subcutaneously, daily (as determined by patient's blood glucose), for 24 weeks
DEVICEHumaPen Memoir
subcutaneously, daily for 24 weeks
DEVICEHumaPen Luxura
subcutaneously, daily for 24 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 1 diabetes mellitus * receiving at least 3 prandial injections per day with short-acting or analogue insulin
Exclusion criteria
* Insulin pump therapy * receiving pre-mixed insulin preparations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 Endpoint | Baseline, Week 24 | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) Mean values were controlled for treatment, visit, treatment\*visit interaction, screening HbA1c (≤9% / \>9%), change of prandial insulin at baseline, and baseline HbA1c. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Hemoglobin A1c (HbA1c) ≤7.5% and ≤7.0% at Week 24 Endpoint | Week 24 | — |
| Score in Insulin Delivery System Questionnaire (IDSQ) - Willingness to Continue at Week 24 Endpoint | Week 24 | IDSQ is used to evaluate acceptance of study pen. Willingness to continue was assessed by a single question, rated from 1 to 5 (1=Definitely unwilling and 5=Definitely willing). Higher score indicates stronger desire to continue. Least Squares (LS) Mean values were controlled for treatment and baseline score. |
| 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes at Any Time From Baseline Through Week 24 | Baseline through Week 24 | Hypoglycemic episode is defined as blood glucose measurement ≤3.9 millimoles/Liter (mmol/L; 70 milligrams/deciliter \[mg/dL\]). Adjusted rate = number of events in study period, divided by number of days in study period, then multiplied by 30. |
| 30-Day Adjusted Rates of Self-Reported Hyperglycemic Episodes at Any Time From Baseline Through Week 24 | Baseline through Week 24 | Hyperglycemic episode is defined as blood glucose measurement \>18 mmol/L (324 mg/dL). Adjusted rate = number of events in study period, divided by number of days in study period, then multiplied by 30. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HumaPen Luxura Participant's insulin dose of Insulin Lispro or Huminsulin Normal is delivered subcutaneously via HumaPen Luxura daily for 24 weeks | 128 |
| HumaPen Memoir Participant's insulin dose of Insulin Lispro or Huminsulin Normal is delivered subcutaneously via HumaPen Memoir daily for 24 weeks | 129 |
| Total | 257 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Sponsor decision | 0 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | HumaPen Luxura | HumaPen Memoir | Total |
|---|---|---|---|
| Age Continuous | 41.2 years STANDARD_DEVIATION 15.52 | 38.3 years STANDARD_DEVIATION 17.37 | 39.8 years STANDARD_DEVIATION 16.5 |
| Hemoglobin A1c (HbA1c) | 9.06 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.93 | 9.12 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.04 | 9.09 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.99 |
| Race/Ethnicity, Customized Black or African American | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized White | 127 participants | 128 participants | 255 participants |
| Region of Enrollment Germany | 128 participants | 129 participants | 257 participants |
| Sex: Female, Male Female | 52 Participants | 56 Participants | 108 Participants |
| Sex: Female, Male Male | 76 Participants | 73 Participants | 149 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 52 / 131 | 50 / 130 |
| serious Total, serious adverse events | 7 / 131 | 8 / 130 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 Endpoint
HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) Mean values were controlled for treatment, visit, treatment\*visit interaction, screening HbA1c (≤9% / \>9%), change of prandial insulin at baseline, and baseline HbA1c.
Time frame: Baseline, Week 24
Population: Participants in full analysis population set with missing values accounted for using mixed model repeated measures (MMRM).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| HumaPen Luxura | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 Endpoint | -0.48 percentage of glycosylated hemoglobin |
| HumaPen Memoir | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 Endpoint | -0.43 percentage of glycosylated hemoglobin |
Comparison: Superiority criterion is met if the upper limit of Confidence Interval (CI) is below zero.p-value: 0.669295% CI: [-0.17, 0.26]Mixed Models Analysis
Secondary
30-Day Adjusted Rates of Self-Reported Hyperglycemic Episodes at Any Time From Baseline Through Week 24
Hyperglycemic episode is defined as blood glucose measurement \>18 mmol/L (324 mg/dL). Adjusted rate = number of events in study period, divided by number of days in study period, then multiplied by 30.
Time frame: Baseline through Week 24
Population: Randomized participants who took at least one dose of study drug with post-baseline hyperglycemia follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HumaPen Luxura | 30-Day Adjusted Rates of Self-Reported Hyperglycemic Episodes at Any Time From Baseline Through Week 24 | 2.56 number of events per 30 days | Standard Deviation 5.5 |
| HumaPen Memoir | 30-Day Adjusted Rates of Self-Reported Hyperglycemic Episodes at Any Time From Baseline Through Week 24 | 3.92 number of events per 30 days | Standard Deviation 9.82 |
p-value: 0.1187Wilcoxon (Mann-Whitney)
Secondary
30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes at Any Time From Baseline Through Week 24
Hypoglycemic episode is defined as blood glucose measurement ≤3.9 millimoles/Liter (mmol/L; 70 milligrams/deciliter \[mg/dL\]). Adjusted rate = number of events in study period, divided by number of days in study period, then multiplied by 30.
Time frame: Baseline through Week 24
Population: Randomized participants who took at least one dose of study drug with post-baseline hypoglycemia follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HumaPen Luxura | 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes at Any Time From Baseline Through Week 24 | 2.68 number of events per 30 days | Standard Deviation 4.66 |
| HumaPen Memoir | 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes at Any Time From Baseline Through Week 24 | 2.46 number of events per 30 days | Standard Deviation 4.38 |
p-value: 0.9817Wilcoxon (Mann-Whitney)
Secondary
Percentage of Participants Achieving Hemoglobin A1c (HbA1c) ≤7.5% and ≤7.0% at Week 24 Endpoint
Time frame: Week 24
Population: Participants in full analysis population set who had Week 24 measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HumaPen Luxura | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) ≤7.5% and ≤7.0% at Week 24 Endpoint | HbA1c ≤7.0% | 5.5 percentage of participants |
| HumaPen Luxura | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) ≤7.5% and ≤7.0% at Week 24 Endpoint | HbA1c ≤7.5% | 16.5 percentage of participants |
| HumaPen Memoir | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) ≤7.5% and ≤7.0% at Week 24 Endpoint | HbA1c ≤7.0% | 3.1 percentage of participants |
| HumaPen Memoir | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) ≤7.5% and ≤7.0% at Week 24 Endpoint | HbA1c ≤7.5% | 11.0 percentage of participants |
p-value: 0.3551Chi-squared
p-value: 0.2026Chi-squared
Secondary
Score in Insulin Delivery System Questionnaire (IDSQ) - Willingness to Continue at Week 24 Endpoint
IDSQ is used to evaluate acceptance of study pen. Willingness to continue was assessed by a single question, rated from 1 to 5 (1=Definitely unwilling and 5=Definitely willing). Higher score indicates stronger desire to continue. Least Squares (LS) Mean values were controlled for treatment and baseline score.
Time frame: Week 24
Population: Participants in full analysis population set who had Week 24 measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| HumaPen Luxura | Score in Insulin Delivery System Questionnaire (IDSQ) - Willingness to Continue at Week 24 Endpoint | 4.06 units on a scale |
| HumaPen Memoir | Score in Insulin Delivery System Questionnaire (IDSQ) - Willingness to Continue at Week 24 Endpoint | 4.05 units on a scale |
p-value: 0.907ANCOVA