Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
Conditions
Keywords
diabetes, type 1, type 2
Brief summary
The purpose of this study is to compare glycemic control (HbA1c) in Chinese patients with type 1 or type 2 diabetes when treated with insulin lispro low mixture and human insulin 30/70.
Interventions
Patient adjusted dose, twice daily (BID), injected subcutaneous (SC) x 12 weeks
DRUGInsulin lispro low mix
Patient adjusted dose, twice daily (BID), injected subcutaneous (SC) x 12 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Clinically diagnosed type 1or type 2 diabetes for at least 2 months * Aged between 18 and 70 (inclusive) * Have been treated with human insulin mix 30/70 twice daily for at least 2 months prior to entering the study * Have glycosylated hemoglobin (Hb1Ac) between 1.2 and 1.7 times the upper limit of normal reference range within 2 weeks prior to or at Visit 1 * Compliance with diet and insulin therapy and performs regular blood glucose monitoring
Exclusion criteria
* Have used oral antidiabetic agents within 30 days prior to entry into the study * Receive a total daily dose of insulin \>2 units/kilogram * Have had more than two episodes of severe hypoglycemia within 6 months prior to entry into the study * Have a body mass index \>35 kilograms per square meter (kg/m2) * Receive chronic systemic glucocorticoid therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycosylated Hemoglobin (HbA1c) Value at 12 Week Endpoint | Baseline and 12 weeks of each treatment | Glycosylated hemoglobin reflects the average blood glucose level over the previous 12 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Blood Glucose Values From Baseline to 12 Weeks of Treatment | Baseline and 12 weeks of each treatment | Values obtained after at least an 8 hour fast. Change = Baseline - Endpoint |
| Change in Total Daily Insulin Dose Values From Baseline to 12 Weeks of Treatment | Baseline and 12 weeks of each treatment | Insulin lispro low mix was to be administered within 15 minutes of morning and evening meals. Human insulin mix 30/70 was to be administered within 30 minutes of morning and evening meals. Change = Baseline - Endpoint |
| Changes in Glycosylated Hemoglobin (HbA1c) From Baseline to 12 Weeks of Treatment | Baseline and at 12 weeks of each treatment | Changes in glycosylated hemoglobin reflect the change in average blood glucose level between baseline and 12 weeks of treatment. Change = Baseline - Endpoint. |
| Number of Participants With Laboratory Parameters Significantly Different From Baseline | Baseline and 12 weeks of each treatment | Number of participants with laboratory parameters (hematology, chemistry, and urinalysis) that were significantly different from baseline after 12 weeks of each treatment. |
| Hypoglycemia Rate Per Participant Per 30 Days | over 12 weeks of each treatment period | Hypoglycemia rate per patient per 30 days = (number of reported hypogylcemia events/number of days within the period) \* 30 days. Since this was a 2x2 cross-over design (2 treatments and 2 periods), then the hypogyclemia rate was calculated per patient for each of the 2 periods by treatment. |
| Number of Participants Achieving Target Glycosylated Hemoglobin (HbA1c) Values <=7% and <=6.5% | 12 weeks of each treatment | Number of patients in each treatment group achieving the target HbA1c value during 12 weeks of each treatment. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Human Insulin Mix 30/70 First, Then Insulin Lispro Low Mix Human insulin mix 30/70 for 12 weeks followed by insulin lispro low mix for 12 weeks | 57 |
| Insulin Lispro Low Mix First, Then Human Insulin Mix 30/70 Insulin lispro low mix for 12 weeks followed by human insulin mix 30/70 for 12 weeks | 60 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
Baseline characteristics
| Characteristic | Insulin Lispro Low Mix First, Then Human Insulin Mix 30/70 | Total | Human Insulin Mix 30/70 First, Then Insulin Lispro Low Mix |
|---|---|---|---|
| Age Continuous | 54.5 years STANDARD_DEVIATION 10.75 | 54.2 years STANDARD_DEVIATION 10.71 | 53.9 years STANDARD_DEVIATION 10.75 |
| Baseline Fasting Blood Glucose | 9.15 millimole/Liter STANDARD_DEVIATION 3.2 | 9.32 millimole/Liter STANDARD_DEVIATION 2.942 | 9.49 millimole/Liter STANDARD_DEVIATION 2.66 |
| Baseline Glycosylated Hemoglobin | 8.59 percent of glycosylated hemoglobin STANDARD_DEVIATION 1.573 | 8.58 percent of glycosylated hemoglobin STANDARD_DEVIATION 1.442 | 8.56 percent of glycosylated hemoglobin STANDARD_DEVIATION 1.304 |
| Body Mass Index | 24.58 kilogram per meter squared STANDARD_DEVIATION 2.754 | 24.98 kilogram per meter squared STANDARD_DEVIATION 3.045 | 25.40 kilogram per meter squared STANDARD_DEVIATION 3.297 |
| Duration of Diabetes | 130.3 months STANDARD_DEVIATION 78.31 | 130.1 months STANDARD_DEVIATION 86.78 | 129.8 months STANDARD_DEVIATION 95.61 |
| Duration of Insulin Treatment | 39.0 months STANDARD_DEVIATION 32.37 | 38.8 months STANDARD_DEVIATION 34.77 | 38.6 months STANDARD_DEVIATION 37.41 |
| Other Treatments for Diabetes Prior to Study No | 37 participants | 72 participants | 35 participants |
| Other Treatments for Diabetes Prior to Study Yes | 23 participants | 45 participants | 22 participants |
| Race/Ethnicity Han - the main ethnic origin in China | 60 participants | 117 participants | 57 participants |
| Region of Enrollment China | 60 participants | 117 participants | 57 participants |
| Sex: Female, Male Female | 35 Participants | 66 Participants | 31 Participants |
| Sex: Female, Male Male | 25 Participants | 51 Participants | 26 Participants |
| Type of Diabetes Type 1 | 7 participants | 9 participants | 2 participants |
| Type of Diabetes Type 2 | 53 participants | 108 participants | 55 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / — | 23 / — |
| serious Total, serious adverse events | 2 / — | 1 / — |
Outcome results
Primary
Glycosylated Hemoglobin (HbA1c) Value at 12 Week Endpoint
Glycosylated hemoglobin reflects the average blood glucose level over the previous 12 weeks of treatment.
Time frame: Baseline and 12 weeks of each treatment
Population: Includes all randomized patients who completed the study with no major protocol violations. Crossover study design allows for the comparison of the effect of two treatments on the same patients, each patient served as own control for between-treatment comparisons. The data from two periods were combined and analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Human Insulin Mix 30/70 | Glycosylated Hemoglobin (HbA1c) Value at 12 Week Endpoint | 7.91 percent of glycosylated hemoglobin | 95% Confidence Interval 1.158 |
| Insulin Lispro Low Mix | Glycosylated Hemoglobin (HbA1c) Value at 12 Week Endpoint | 7.96 percent of glycosylated hemoglobin | 95% Confidence Interval 1.373 |
Comparison: Mixed model where period, sequence, treatment are fixed effects and patient within sequence are random effects.p-value: 0.49795% CI: [-0.2, 0.1]Mixed Models Analysis
Secondary
Change in Fasting Blood Glucose Values From Baseline to 12 Weeks of Treatment
Values obtained after at least an 8 hour fast. Change = Baseline - Endpoint
Time frame: Baseline and 12 weeks of each treatment
Population: Includes all randomized patients who completed the study with no major protocol violations. Crossover study design allows for the comparison of the effect of two treatments on the same patients, each patient served as own control for between-treatment comparisons. The data from two periods were combined and analyzed. LOCF within each period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Human Insulin Mix 30/70 | Change in Fasting Blood Glucose Values From Baseline to 12 Weeks of Treatment | 1.04 millimoles/Liter |
| Insulin Lispro Low Mix | Change in Fasting Blood Glucose Values From Baseline to 12 Weeks of Treatment | 1.18 millimoles/Liter |
p-value: 0.41995% CI: [-0.48, 0.2]Mixed Models Analysis
Secondary
Change in Total Daily Insulin Dose Values From Baseline to 12 Weeks of Treatment
Insulin lispro low mix was to be administered within 15 minutes of morning and evening meals. Human insulin mix 30/70 was to be administered within 30 minutes of morning and evening meals. Change = Baseline - Endpoint
Time frame: Baseline and 12 weeks of each treatment
Population: Includes all randomized patients who completed the study with no major protocol violations. Crossover study design allows for the comparison of the effect of two treatments on the same patients, each patient served as own control for between-treatment comparisons. The data from two periods were combined and analyzed. LOCF within each period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Human Insulin Mix 30/70 | Change in Total Daily Insulin Dose Values From Baseline to 12 Weeks of Treatment | -4.72 units of insulin |
| Insulin Lispro Low Mix | Change in Total Daily Insulin Dose Values From Baseline to 12 Weeks of Treatment | -4.56 units of insulin |
p-value: 0.74195% CI: [-1.09, 0.78]Mixed Models Analysis
Secondary
Changes in Glycosylated Hemoglobin (HbA1c) From Baseline to 12 Weeks of Treatment
Changes in glycosylated hemoglobin reflect the change in average blood glucose level between baseline and 12 weeks of treatment. Change = Baseline - Endpoint.
Time frame: Baseline and at 12 weeks of each treatment
Population: Includes all randomized patients who completed the study with no major protocol violations. Crossover study design allows for the comparison of the effect of two treatments on the same patients, each patient served as own control for between-treatment comparisons. The data from two periods were combined and analyzed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Human Insulin Mix 30/70 | Changes in Glycosylated Hemoglobin (HbA1c) From Baseline to 12 Weeks of Treatment | 0.68 percent of glycosylated hemoglobin |
| Insulin Lispro Low Mix | Changes in Glycosylated Hemoglobin (HbA1c) From Baseline to 12 Weeks of Treatment | 0.63 percent of glycosylated hemoglobin |
p-value: 0.49795% CI: [-0.1, 0.2]Mixed Models Analysis
Secondary
Hypoglycemia Rate Per Participant Per 30 Days
Hypoglycemia rate per patient per 30 days = (number of reported hypogylcemia events/number of days within the period) \* 30 days. Since this was a 2x2 cross-over design (2 treatments and 2 periods), then the hypogyclemia rate was calculated per patient for each of the 2 periods by treatment.
Time frame: over 12 weeks of each treatment period
Population: Includes all randomized patients who had at least one dose. Crossover study design allows for the comparison of the effect of two treatments on the same patients, each patient served as own control for between-treatment comparisons. The data from two periods were combined and analyzed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Human Insulin Mix 30/70 | Hypoglycemia Rate Per Participant Per 30 Days | 0.34 events/30 days |
| Insulin Lispro Low Mix | Hypoglycemia Rate Per Participant Per 30 Days | 0.37 events/30 days |
p-value: 0.6795% CI: [-0.16, 0.11]Mixed Models Analysis
Secondary
Number of Participants Achieving Target Glycosylated Hemoglobin (HbA1c) Values <=7% and <=6.5%
Number of patients in each treatment group achieving the target HbA1c value during 12 weeks of each treatment.
Time frame: 12 weeks of each treatment
Population: Includes all randomized patients who completed the study with no major protocol violations. Crossover study design allows for the comparison of the effect of two treatments on the same patients, each patient served as own control for between-treatment comparisons. The data from two periods were combined and analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Human Insulin Mix 30/70 | Number of Participants Achieving Target Glycosylated Hemoglobin (HbA1c) Values <=7% and <=6.5% | HbA1c <=7% | 26 participants |
| Human Insulin Mix 30/70 | Number of Participants Achieving Target Glycosylated Hemoglobin (HbA1c) Values <=7% and <=6.5% | HbA1c <=6.5% | 11 participants |
| Insulin Lispro Low Mix | Number of Participants Achieving Target Glycosylated Hemoglobin (HbA1c) Values <=7% and <=6.5% | HbA1c <=7% | 30 participants |
| Insulin Lispro Low Mix | Number of Participants Achieving Target Glycosylated Hemoglobin (HbA1c) Values <=7% and <=6.5% | HbA1c <=6.5% | 14 participants |
p-value: 0.644Fisher Exact
p-value: 0.672Fisher Exact
Secondary
Number of Participants With Laboratory Parameters Significantly Different From Baseline
Number of participants with laboratory parameters (hematology, chemistry, and urinalysis) that were significantly different from baseline after 12 weeks of each treatment.
Time frame: Baseline and 12 weeks of each treatment
Population: Includes all randomized patients receiving at least one dose. Crossover study design allows for the comparison of the effect of two treatments on the same patients, each patient served as own control for between-treatment comparisons. The data from two periods were combined and analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Human Insulin Mix 30/70 | Number of Participants With Laboratory Parameters Significantly Different From Baseline | Hematology - Significantly Different from Baseline | 0 participants |
| Human Insulin Mix 30/70 | Number of Participants With Laboratory Parameters Significantly Different From Baseline | Chemistry - Significantly Different from Baseline | 0 participants |
| Human Insulin Mix 30/70 | Number of Participants With Laboratory Parameters Significantly Different From Baseline | Urinalysis - Significantly Different from Baseline | 0 participants |
| Insulin Lispro Low Mix | Number of Participants With Laboratory Parameters Significantly Different From Baseline | Hematology - Significantly Different from Baseline | 0 participants |
| Insulin Lispro Low Mix | Number of Participants With Laboratory Parameters Significantly Different From Baseline | Chemistry - Significantly Different from Baseline | 0 participants |
| Insulin Lispro Low Mix | Number of Participants With Laboratory Parameters Significantly Different From Baseline | Urinalysis - Significantly Different from Baseline | 0 participants |