Diabetes Mellitus, Type 2
Conditions
Brief summary
The purpose is to evaluate the proportion of subjects achieving a Hemoglobin A1c (HbA1c) level below 6.5%, when lispro mix 50/50 is introduced in a stepwise manner from every day (QD) administration to type 2 diabetic patients who have failed to achieve adequate glycemic control on oral antidiabetic drugs (OADs).
Detailed description
A multicenter, non-randomized, open-label, post-marketing clinical study. The target population of the study is type 2 diabetic patients who have failed to achieve adequate glycemic control on OADs. The study consists of 4 periods: Lead-in Period (2 to 4 weeks), Study Period I (16 weeks), Study Period II (16 weeks), and Study Period III (16 weeks). The regimen of lispro mix 50/50 injection will be changed every 16 weeks based on the HbA1c level. During Study Period I, all the subjects will be given a once daily (QD) injection of lispro mix 50/50. During Study Period II, the regimen of lispro mix 50/50 injection will be changed to twice daily (BID) if the HbA1c level at Week 16 is 6.5% or above, and QD injection will be continued if the value is below 6.5%. During Study Period III, if the HbA1c level at Week 32 is 6.5% or above, the subjects on BID treatment during the previous period (Study Period II) will receive three times daily (TID) injections of insulin.
Interventions
DRUGLispro Mix 50/50
Administered subcutaneously once daily for 16 weeks, twice daily for 16 weeks, and three times daily for 16 weeks dependent on glycemic control.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed as having type 2 Diabetes. * Patients who have not been on insulin treatment within 6 months. * Patients who have been taking OADs for at least 90 days. * Patients with an HbA1c level in the range of 7.5% to 11.0%. * Patients with a Body-Mass Index (BMI) of 35 kg/m² or below.
Exclusion criteria
* Patients having pre-proliferative or proliferative retinopathy (except for old retinopathy with no need for treatment). * Patients having or suspected of having malignancy * Patients having serious complications of the heart, liver, or kidney. * Patients hypersensitive or allergic to insulin or insulin analog preparations or a history of it. * Patients receiving systemic steroids. * Are currently enrolled in a clinical trial of a non-approved drug. Or patients who participated in other clinical trials including post-marketing clinical trials within 90 days prior to informed consent being obtained. * Patients of child-bearing potential. Breastfeeding patients. Patients with a positive result in a pregnancy test performed for women of child-bearing potential.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 6.5% at Week 48 Endpoint | Week 48 | Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The 6.5% HbA1c is the Japan Diabetes Society (JDS) value, and is equivalent to the National Glycohemoglobin Standardization Program (NGSP) HbA1c value of 6.9%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 7.0% at Week 16, 32 and 48 Endpoints | Week 16 and Week 32 and Week 48 | Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The 7.0% HbA1c is the Japan Diabetes Society (JDS) value, and is equivalent to the National Glycohemoglobin Standardization Program (NGSP) HbA1c value of 7.4%. |
| Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Level Below 6.5% and Below 7.0% by Regimen at Week 48 Endpoint | Week 48 | Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. 6.5% and 7.0% HbA1c are the Japan Diabetes Society (JDS) values, and are equivalent to the National Glycohemoglobin Standardization Program (NGSP) HbA1c values of 6.9% and 7.4%, respectively. |
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 48 Endpoint | Baseline, Week 48 | Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. |
| Change From Baseline in Fasting Glucose at Week 48 Endpoint | Baseline, Week 48 | — |
| Change From Baseline in Blood Glucose Profile at Week 48 Endpoint | Baseline, Week 48 | Time course of changes in blood glucose was determined by 7-point self-monitoring of blood glucose (SMBG) during the day (before breakfast, lunch, and dinner, 2 hours after the start of each meal, and at bedtime). |
| Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 6.5% at Week 16 and Week 32 Endpoints | Week 16 and Week 32 | Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The 6.5% HbA1c is the Japan Diabetes Society (JDS) value, and is equivalent to the National Glycohemoglobin Standardization Program (NGSP) HbA1c value of 6.9%. |
| Change From Baseline in Fasting Serum Lipids at Week 48 Endpoint | Baseline, Week 48 | — |
| Change From Baseline in Body Weight at Week 48 Endpoint | Baseline, Week 48 | — |
| Total Daily Dose of Insulin at Baseline, Week 16, Week 32 and Week 48 | Baseline and Weeks 16, 32 and 48 | — |
| Percentage of Participants Developing Hypoglycemia at Any Time From Baseline Through Week 48 | Baseline through Week 48 | Results are reported as the percentage of participants experiencing hypoglycemia, which was considered any hypoglycemic event in which participants themselves recognized hypoglycemia-related signs and symptoms, or they had a blood glucose level below 50 milligram/deciliter (mg/dL) regardless of signs, symptoms or the relationship to treatment. |
| Number of Hypoglycemia Episodes Participants Experienced at Any Time From Baseline Through Week 48 | Baseline through Week 48 | A hypoglycemic episode was considered any hypoglycemic event in which participants themselves recognized hypoglycemia-related signs and symptoms, or participants had a blood glucose level below 50 mg/dL regardless of signs, symptoms or the relationship to treatment. |
| Change From Baseline in Fasting C-Peptide at Week 48 to Endpoint | Baseline, Week 48 | C-peptide is a protein that is produced in the body along with insulin. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lispro 50/50 Administered subcutaneously once daily for 16 weeks, twice daily for 16 weeks, and three times daily for 16 weeks dependent on glycemic control | 135 |
| Total | 135 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 1 |
| Overall Study | Physician Decision | 7 |
| Overall Study | Protocol Violation | 4 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Lispro 50/50 |
|---|---|
| Age Continuous | 60.3 years STANDARD_DEVIATION 10.2 |
| Race/Ethnicity, Customized Japanese | 135 participants |
| Region of Enrollment Japan | 135 participants |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 106 / 135 |
| serious Total, serious adverse events | 7 / 135 |
Outcome results
Primary
Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 6.5% at Week 48 Endpoint
Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The 6.5% HbA1c is the Japan Diabetes Society (JDS) value, and is equivalent to the National Glycohemoglobin Standardization Program (NGSP) HbA1c value of 6.9%.
Time frame: Week 48
Population: Participants received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lispro 50/50 | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 6.5% at Week 48 Endpoint | 18.5 percentage of participants |
Secondary
Change From Baseline in Blood Glucose Profile at Week 48 Endpoint
Time course of changes in blood glucose was determined by 7-point self-monitoring of blood glucose (SMBG) during the day (before breakfast, lunch, and dinner, 2 hours after the start of each meal, and at bedtime).
Time frame: Baseline, Week 48
Population: Participants received at least one dose of the study drug, and had both baseline and post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lispro 50/50 | Change From Baseline in Blood Glucose Profile at Week 48 Endpoint | After dinner (n=97) | -55.9 mg/dL | Standard Deviation 96.7 |
| Lispro 50/50 | Change From Baseline in Blood Glucose Profile at Week 48 Endpoint | Before breakfast (n=100) | -25.4 mg/dL | Standard Deviation 55 |
| Lispro 50/50 | Change From Baseline in Blood Glucose Profile at Week 48 Endpoint | After breakfast (n=98) | -58.6 mg/dL | Standard Deviation 87.6 |
| Lispro 50/50 | Change From Baseline in Blood Glucose Profile at Week 48 Endpoint | Before lunch (n=100) | -40.6 mg/dL | Standard Deviation 73.1 |
| Lispro 50/50 | Change From Baseline in Blood Glucose Profile at Week 48 Endpoint | After lunch (n=99) | -44.0 mg/dL | Standard Deviation 84.5 |
| Lispro 50/50 | Change From Baseline in Blood Glucose Profile at Week 48 Endpoint | Before dinner (n=100) | -40.0 mg/dL | Standard Deviation 76.8 |
| Lispro 50/50 | Change From Baseline in Blood Glucose Profile at Week 48 Endpoint | Bedtime (n=91) | -56.6 mg/dL | Standard Deviation 75.3 |
Secondary
Change From Baseline in Body Weight at Week 48 Endpoint
Time frame: Baseline, Week 48
Population: Participants who completed treatment through Week 48, and had both baseline and post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lispro 50/50 | Change From Baseline in Body Weight at Week 48 Endpoint | 1.51 kilogram (kg) | Standard Deviation 3.18 |
Secondary
Change From Baseline in Fasting C-Peptide at Week 48 to Endpoint
C-peptide is a protein that is produced in the body along with insulin.
Time frame: Baseline, Week 48
Population: Participants received at least one dose of the study drug, and had both baseline and post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lispro 50/50 | Change From Baseline in Fasting C-Peptide at Week 48 to Endpoint | -0.339 nanogram/milliliter (ng/mL) | Standard Deviation 0.739 |
Secondary
Change From Baseline in Fasting Glucose at Week 48 Endpoint
Time frame: Baseline, Week 48
Population: Participants received at least one dose of the study drug, and had both baseline and post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lispro 50/50 | Change From Baseline in Fasting Glucose at Week 48 Endpoint | -19.9 milligram/deciliter (mg/dL) | Standard Deviation 48.3 |
Secondary
Change From Baseline in Fasting Serum Lipids at Week 48 Endpoint
Time frame: Baseline, Week 48
Population: Participants received at least one dose of the study drug, and had both baseline and post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lispro 50/50 | Change From Baseline in Fasting Serum Lipids at Week 48 Endpoint | Total cholesterol (n=131) | 1.6 mg/dL | Standard Deviation 25.2 |
| Lispro 50/50 | Change From Baseline in Fasting Serum Lipids at Week 48 Endpoint | High-density lipoprotein (HDL) cholesterol (n=130) | 2.44 mg/dL | Standard Deviation 8.66 |
| Lispro 50/50 | Change From Baseline in Fasting Serum Lipids at Week 48 Endpoint | Triglycerides (n=131) | -0.5 mg/dL | Standard Deviation 70.4 |
Secondary
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 48 Endpoint
Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time frame: Baseline, Week 48
Population: Participants received at least one dose of the study drug, and had both baseline and post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lispro 50/50 | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 48 Endpoint | -1.27 percentage of glycosylated hemoglobin | Standard Deviation 0.98 |
Secondary
Number of Hypoglycemia Episodes Participants Experienced at Any Time From Baseline Through Week 48
A hypoglycemic episode was considered any hypoglycemic event in which participants themselves recognized hypoglycemia-related signs and symptoms, or participants had a blood glucose level below 50 mg/dL regardless of signs, symptoms or the relationship to treatment.
Time frame: Baseline through Week 48
Population: Participants received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lispro 50/50 | Number of Hypoglycemia Episodes Participants Experienced at Any Time From Baseline Through Week 48 | 535 number of hypoglycemic episodes |
Secondary
Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 6.5% at Week 16 and Week 32 Endpoints
Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The 6.5% HbA1c is the Japan Diabetes Society (JDS) value, and is equivalent to the National Glycohemoglobin Standardization Program (NGSP) HbA1c value of 6.9%.
Time frame: Week 16 and Week 32
Population: Participants received at least one dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lispro 50/50 | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 6.5% at Week 16 and Week 32 Endpoints | Week 16 | 6.7 percentage of participants |
| Lispro 50/50 | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 6.5% at Week 16 and Week 32 Endpoints | Week 32 | 20.0 percentage of participants |
Secondary
Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 7.0% at Week 16, 32 and 48 Endpoints
Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The 7.0% HbA1c is the Japan Diabetes Society (JDS) value, and is equivalent to the National Glycohemoglobin Standardization Program (NGSP) HbA1c value of 7.4%.
Time frame: Week 16 and Week 32 and Week 48
Population: Participants received at least one dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lispro 50/50 | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 7.0% at Week 16, 32 and 48 Endpoints | Week 16 | 22.2 percentage of participants |
| Lispro 50/50 | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 7.0% at Week 16, 32 and 48 Endpoints | Week 32 | 43.0 percentage of participants |
| Lispro 50/50 | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 7.0% at Week 16, 32 and 48 Endpoints | Week 48 | 52.6 percentage of participants |
Secondary
Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Level Below 6.5% and Below 7.0% by Regimen at Week 48 Endpoint
Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. 6.5% and 7.0% HbA1c are the Japan Diabetes Society (JDS) values, and are equivalent to the National Glycohemoglobin Standardization Program (NGSP) HbA1c values of 6.9% and 7.4%, respectively.
Time frame: Week 48
Population: Participants completed treatment through Week 48.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lispro 50/50 | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Level Below 6.5% and Below 7.0% by Regimen at Week 48 Endpoint | Below 6.5% | 22.2 percentage of participants |
| Lispro 50/50 | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Level Below 6.5% and Below 7.0% by Regimen at Week 48 Endpoint | Below 7.0% | 77.8 percentage of participants |
| Lispro 50/50 Twice Daily | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Level Below 6.5% and Below 7.0% by Regimen at Week 48 Endpoint | Below 6.5% | 61.9 percentage of participants |
| Lispro 50/50 Twice Daily | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Level Below 6.5% and Below 7.0% by Regimen at Week 48 Endpoint | Below 7.0% | 95.2 percentage of participants |
| Lispro 50/50 Three Times Daily | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Level Below 6.5% and Below 7.0% by Regimen at Week 48 Endpoint | Below 6.5% | 11.6 percentage of participants |
| Lispro 50/50 Three Times Daily | Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Level Below 6.5% and Below 7.0% by Regimen at Week 48 Endpoint | Below 7.0% | 51.2 percentage of participants |
Secondary
Percentage of Participants Developing Hypoglycemia at Any Time From Baseline Through Week 48
Results are reported as the percentage of participants experiencing hypoglycemia, which was considered any hypoglycemic event in which participants themselves recognized hypoglycemia-related signs and symptoms, or they had a blood glucose level below 50 milligram/deciliter (mg/dL) regardless of signs, symptoms or the relationship to treatment.
Time frame: Baseline through Week 48
Population: Participants received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lispro 50/50 | Percentage of Participants Developing Hypoglycemia at Any Time From Baseline Through Week 48 | 65.9 percentage of participants |
Secondary
Total Daily Dose of Insulin at Baseline, Week 16, Week 32 and Week 48
Time frame: Baseline and Weeks 16, 32 and 48
Population: Participants who completed treatment through Week 48.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lispro 50/50 | Total Daily Dose of Insulin at Baseline, Week 16, Week 32 and Week 48 | Baseline | 4.34 units of insulin/day | Standard Deviation 1.35 |
| Lispro 50/50 | Total Daily Dose of Insulin at Baseline, Week 16, Week 32 and Week 48 | Week 16 | 9.94 units of insulin/day | Standard Deviation 4.91 |
| Lispro 50/50 | Total Daily Dose of Insulin at Baseline, Week 16, Week 32 and Week 48 | Week 32 | 15.92 units of insulin/day | Standard Deviation 10.01 |
| Lispro 50/50 | Total Daily Dose of Insulin at Baseline, Week 16, Week 32 and Week 48 | Week 48 | 19.42 units of insulin/day | Standard Deviation 13.64 |