Diabetes Mellitus, Type 1
Conditions
Brief summary
Comparison of blood glucose levels in patients with Type 1 diabetes when they take a new basal insulin analog and when they take insulin glargine
Detailed description
Prestudy treatment for patients who enter this study will be once daily insulin glargine along with mealtime insulins. Patients will continue to use their mealtime insulins throughout the study. The study will consist of 16 weeks of treatment and 4 weeks of follow-up. The 16 weeks of treatment will consist of two 8-week periods (Periods 1 and 2) during which patients will receive insulin glargine for 8 weeks and LY2605541 for 8 weeks in a random sequence. During the 4-week follow-up period, patients will return to insulin glargine or another basal insulin recommended by the investigator.
Interventions
DRUGLY2605541
Administered subcutaneously every morning with dose titration based on blood glucose measures for 8 weeks in each of 2 study periods.
DRUGInsulin glargine
Administered subcutaneously every morning with dose titration based on blood glucose measures for 8 weeks in each of 2 study periods.
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Type 1 diabetes mellitus (T1DM) for at least 1 year and using insulin glargine for at least 6 months with a maximum daily dose of 1 unit per kilogram (U/kg). * Hemoglobin A1c (HbA1c) of no greater than 10.5% before randomization * Body mass index (BMI) 19 to 45 kilogram per square meter (kg/m²) * Capable and willing to prepare and inject insulin with a syringe, monitor own blood glucose, complete the study diary, be receptive to diabetes education, comply with study requirements, and receive telephone calls during treatment * Women of childbearing potential must test negative for pregnancy before receiving treatment and agree to use reliable birth control until completing the follow-up
Exclusion criteria
* Twice daily use of insulin glargine within 30 days prior to the study * Use of any oral or injectable medication intended for the treatment of diabetes mellitus other than insulins in the 3 months prior to the study * Use of an insulin pump * More than 1 episode of severe hypoglycemia within 3 months prior to the study, or currently diagnosed as having hypoglycemia unawareness * 2 or more emergency room visits or hospitalizations due to poor glucose control in the 6 months preceding the study * Known hypersensitivity or allergy to any of the study insulins or their excipients * Blood transfusion or severe blood loss within 3 months prior to the study or known hemoglobinopathy, hemolytic anemia, or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the HbA1c methodology * Irregular sleep/wake cycle * Pregnant or intend to become pregnant during the study * Women who are breastfeeding * Use of prescription or over-the-counter medications to promote weight loss within 3 months prior to the study * Current participation in a weight loss program or plans to do so during the study * Use of chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy currently or within 4 weeks prior to the study * Cardiac disease with a marked impact on physical functioning * Clinically significant electrocardiogram (ECG) abnormalities at screening * Fasting triglycerides greater than 500 milligram per deciliter (mg/dL) * Liver disease * History of renal transplantation, current renal dialysis, or creatinine greater than 2.0 mg/dL (177 micromole per liter \[μmol/L\]) * Malignancy other than basal cell or squamous cell skin cancer, currently or within the last 5 years * Treatment with any antibody-based therapy within 6 months prior to the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily Average Blood Glucose (Avg. BG) at Week 8 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles | Week 8 of each treatment period | It is the Avg. of the 8-point SMBG profiles, BG of morning fasting, midday & evening pre-meal, 2-hour postprandial after each of the 3 main meals, bedtime, 0300 hours. Least squares (LS) mean of daily Avg. BG is from mixed-model repeated measures (MMRM), which includes fixed effects of treatment (LY2605541, Glargine); Treatment Sequence; treatment period; dose conversion (pre-interim analysis \[IA\], post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline Hemoglobin \[HbA1c\] group); visit; visit and treatment interaction; a random effect for participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin (HbA1c) at Week 8 Endpoint of Period I | Baseline, Week 8 (Period I) | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean of the change from baseline to 8-week at Period I is from MMRM approach, which includes fixed effects of treatment (LY2605541, Glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group); baseline HbA1c; visit; interaction between visit and treatment; and a random effect for participant. |
| Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 8 Endpoint of Period I | Week 8 (Period I) | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. |
| Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 8 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment (Period I) | Week 8 (Period I) | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 millimole/Liter (mmol/L) (≤70 milligram/deciliter \[mg/dL\]) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]). |
| 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Week 8 of each treatment period | 8-point SMBG profiles are measured at morning fasting BG (FBG), midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean is obtained from MMRM approach, which includes fixed effects of treatment (LY2605541, Glargine); treatment sequence; treatment period; dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; interaction between visit and treatment; and a random effect for participant. |
| Daily Basal Insulin Dose at Week 2 and Week 8 Endpoint | Week 2 and Week 8 of each treatment period | LS mean is obtained from MMRM approach, which includes fixed effects of treatment (LY2605541, Glargine); treatment sequence; treatment period; dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; interaction between visit and treatment; and a random effect for participant. |
| Change From Baseline in Daily Average Blood Glucose (Avg. BG) at Week 8 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles | Baseline, Week 8 of each treatment period | It is the Avg. of the 8-point SMBG profiles, BG of morning fasting, midday & evening pre-meal, 2-hour postprandial after each of the 3 main meals, bedtime, 0300 hours. LS mean of daily Avg. BG is from MMRM, which includes fixed effects of treatment (LY2605541, Glargine); Treatment Sequence; treatment period; dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; a random effect for participant. |
| Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 8, Week 16 and Week 20 | Negative is defined as either 'negative' from lab or percent binding \<1.16%. Positive is defined as the percent binding is ≥1.16%. The antibody status change is from negative to positive or positive to negative. |
| Percentage of Participants With Hypoglycemia Baseline Through Week 8 | Baseline through Week 8 of each treatment period | Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 millimole per Liter (mmol/L) (≤70 milligram per deciliter \[mg/dL\]) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]. |
| Rate of Hypoglycemia Per 30 Days Baseline Through Week 8 | Baseline through Week 8 of each treatment period | Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]. Hypoglycemia rate per 30 days is calculated as the number of hypoglycemia/number of days at risk\*30. |
| Glycemic Variability in Fasting Blood Glucose (FBG) at Week 8 Endpoint | Week 8 of each treatment period | Within-patient glycemic variability was assessed as the standard deviation of fasting blood glucose each day between Week 6 and Week 8. LS mean is obtained from MMRM approach, which includes fixed effects of treatment (LY2605541, Glargine); treatment sequence; treatment period; dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; interaction between visit and treatment; and a random effect for participant. |
| Pharmacokinetics - Drug (LY2605541) Concentration at Steady State (Css) at Week 8 Endpoint | Week 8 of each treatment period | The drug (LY2605541) concentration at steady state (Css) is calculated from the clearance (Liter/hour) and the final dose of the participants. Clearance was estimated using population-based approaches. |
Countries
Israel, United States
Participant flow
Pre-assignment details
This is an open-label, randomized, 2-arm crossover study. The study consisted of two 8-week periods (Periods I and II) during which participants received Glargine for 8 weeks and LY2605541 for 8 weeks in a random sequence.
Participants by arm
| Arm | Count |
|---|---|
| LY2605541/Glargine Participants took LY2605541 in Period I and Glargine in Period II | 69 |
| Glargine/LY2605541 Participants took Glargine in Period I and LY2605541 in Period II | 68 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period I | Adverse Event | 1 | 0 |
| Period I | Lost to Follow-up | 2 | 2 |
| Period I | Physician Decision | 0 | 3 |
| Period I | Protocol Violation | 1 | 2 |
| Period I | Withdrawal by Subject | 4 | 6 |
| Period II | Adverse Event | 1 | 0 |
| Period II | Lost to Follow-up | 1 | 0 |
| Period II | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | LY2605541/Glargine | Glargine/LY2605541 | Total |
|---|---|---|---|
| Age, Continuous | 36.82 years STANDARD_DEVIATION 11.34 | 39.53 years STANDARD_DEVIATION 12.28 | 38.17 years STANDARD_DEVIATION 11.85 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 65 Participants | 64 Participants | 129 Participants |
| Region of Enrollment Israel | 7 Participants | 4 Participants | 11 Participants |
| Region of Enrollment United States | 62 Participants | 64 Participants | 126 Participants |
| Sex: Female, Male Female | 28 Participants | 23 Participants | 51 Participants |
| Sex: Female, Male Male | 41 Participants | 45 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 66 / 125 | 59 / 130 |
| serious Total, serious adverse events | 6 / 125 | 4 / 130 |
Outcome results
Primary
Daily Average Blood Glucose (Avg. BG) at Week 8 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles
It is the Avg. of the 8-point SMBG profiles, BG of morning fasting, midday & evening pre-meal, 2-hour postprandial after each of the 3 main meals, bedtime, 0300 hours. Least squares (LS) mean of daily Avg. BG is from mixed-model repeated measures (MMRM), which includes fixed effects of treatment (LY2605541, Glargine); Treatment Sequence; treatment period; dose conversion (pre-interim analysis \[IA\], post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline Hemoglobin \[HbA1c\] group); visit; visit and treatment interaction; a random effect for participant.
Time frame: Week 8 of each treatment period
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Daily Average Blood Glucose (Avg. BG) at Week 8 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles | 7.98 millimole per Liter (mmol/L) | Standard Error 0.32 |
| Glargine | Daily Average Blood Glucose (Avg. BG) at Week 8 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles | 8.53 millimole per Liter (mmol/L) | Standard Error 0.33 |
p-value: <0.00190% CI: [-0.81, -0.29]Mixed Models Analysis
Secondary
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint
8-point SMBG profiles are measured at morning fasting BG (FBG), midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean is obtained from MMRM approach, which includes fixed effects of treatment (LY2605541, Glargine); treatment sequence; treatment period; dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; interaction between visit and treatment; and a random effect for participant.
Time frame: Week 8 of each treatment period
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2605541 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | 0300 hours BG | 8.97 mmol/L | Standard Error 0.5 |
| LY2605541 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Morning FBG | 9.33 mmol/L | Standard Error 0.45 |
| LY2605541 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Morning 2-hr postprandial BG | 8.27 mmol/L | Standard Error 0.46 |
| LY2605541 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Midday Pre-meal BG | 6.98 mmol/L | Standard Error 0.43 |
| LY2605541 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Midday 2-hr postprandial BG | 8.08 mmol/L | Standard Error 0.44 |
| LY2605541 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Evening Pre-meal BG | 7.87 mmol/L | Standard Error 0.38 |
| LY2605541 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Evening 2-hr postprandial BG | 8.37 mmol/L | Standard Error 0.44 |
| LY2605541 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Bed time BG | 8.20 mmol/L | Standard Error 0.45 |
| Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Bed time BG | 9.29 mmol/L | Standard Error 0.48 |
| Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | 0300 hours BG | 8.67 mmol/L | Standard Error 0.51 |
| Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Midday 2-hr postprandial BG | 8.60 mmol/L | Standard Error 0.47 |
| Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Morning FBG | 9.57 mmol/L | Standard Error 0.49 |
| Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Evening 2-hr postprandial BG | 9.26 mmol/L | Standard Error 0.46 |
| Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Morning 2-hr postprandial BG | 8.76 mmol/L | Standard Error 0.46 |
| Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Evening Pre-meal BG | 8.73 mmol/L | Standard Error 0.41 |
| Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 8 Endpoint | Midday Pre-meal BG | 7.52 mmol/L | Standard Error 0.45 |
p-value: 0.39290% CI: [-0.28, 0.88]Mixed Models Analysis
p-value: 0.46490% CI: [-0.79, 0.3]Mixed Models Analysis
p-value: 0.15190% CI: [-1.04, 0.07]Mixed Models Analysis
p-value: 0.07990% CI: [-1.05, -0.03]Mixed Models Analysis
p-value: 0.0790% CI: [-0.99, -0.05]Mixed Models Analysis
p-value: 0.00890% CI: [-1.39, -0.34]Mixed Models Analysis
p-value: 0.00390% CI: [-1.38, -0.41]Mixed Models Analysis
p-value: 0.00190% CI: [-1.64, -0.55]Mixed Models Analysis
Secondary
Change From Baseline in Daily Average Blood Glucose (Avg. BG) at Week 8 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles
It is the Avg. of the 8-point SMBG profiles, BG of morning fasting, midday & evening pre-meal, 2-hour postprandial after each of the 3 main meals, bedtime, 0300 hours. LS mean of daily Avg. BG is from MMRM, which includes fixed effects of treatment (LY2605541, Glargine); Treatment Sequence; treatment period; dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; a random effect for participant.
Time frame: Baseline, Week 8 of each treatment period
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Change From Baseline in Daily Average Blood Glucose (Avg. BG) at Week 8 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles | -0.74 mmol/L | Standard Error 0.4 |
| Glargine | Change From Baseline in Daily Average Blood Glucose (Avg. BG) at Week 8 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles | -0.18 mmol/L | Standard Error 0.4 |
p-value: <0.00190% CI: [-0.83, -0.29]Mixed Models Analysis
Secondary
Change From Baseline in Hemoglobin (HbA1c) at Week 8 Endpoint of Period I
HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean of the change from baseline to 8-week at Period I is from MMRM approach, which includes fixed effects of treatment (LY2605541, Glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group); baseline HbA1c; visit; interaction between visit and treatment; and a random effect for participant.
Time frame: Baseline, Week 8 (Period I)
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Change From Baseline in Hemoglobin (HbA1c) at Week 8 Endpoint of Period I | -0.45 percentage of glycated hemoglobin | Standard Error 0.1 |
| Glargine | Change From Baseline in Hemoglobin (HbA1c) at Week 8 Endpoint of Period I | -0.34 percentage of glycated hemoglobin | Standard Error 0.11 |
p-value: 0.24290% CI: [-0.28, 0.05]Mixed Models Analysis
Secondary
Daily Basal Insulin Dose at Week 2 and Week 8 Endpoint
LS mean is obtained from MMRM approach, which includes fixed effects of treatment (LY2605541, Glargine); treatment sequence; treatment period; dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; interaction between visit and treatment; and a random effect for participant.
Time frame: Week 2 and Week 8 of each treatment period
Population: All randomized participants who took at least one dose of study drug with at least one non-missing value of the response variable at any of the subsequent weeks.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2605541 | Daily Basal Insulin Dose at Week 2 and Week 8 Endpoint | Week 2 | 3.35 nanomoles per kilogram (nmoles/kg) | Standard Deviation 0.16 |
| LY2605541 | Daily Basal Insulin Dose at Week 2 and Week 8 Endpoint | Week 8 | 4.12 nanomoles per kilogram (nmoles/kg) | Standard Deviation 0.18 |
| Glargine | Daily Basal Insulin Dose at Week 2 and Week 8 Endpoint | Week 2 | 2.58 nanomoles per kilogram (nmoles/kg) | Standard Deviation 0.16 |
| Glargine | Daily Basal Insulin Dose at Week 2 and Week 8 Endpoint | Week 8 | 2.86 nanomoles per kilogram (nmoles/kg) | Standard Deviation 0.16 |
Secondary
Glycemic Variability in Fasting Blood Glucose (FBG) at Week 8 Endpoint
Within-patient glycemic variability was assessed as the standard deviation of fasting blood glucose each day between Week 6 and Week 8. LS mean is obtained from MMRM approach, which includes fixed effects of treatment (LY2605541, Glargine); treatment sequence; treatment period; dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; interaction between visit and treatment; and a random effect for participant.
Time frame: Week 8 of each treatment period
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Glycemic Variability in Fasting Blood Glucose (FBG) at Week 8 Endpoint | 3.13 mmol/L | Standard Error 0.23 |
| Glargine | Glycemic Variability in Fasting Blood Glucose (FBG) at Week 8 Endpoint | 3.60 mmol/L | Standard Error 0.24 |
p-value: <0.00190% CI: [-0.69, -0.25]Mixed Models Analysis
Secondary
Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20
Negative is defined as either 'negative' from lab or percent binding \<1.16%. Positive is defined as the percent binding is ≥1.16%. The antibody status change is from negative to positive or positive to negative.
Time frame: Week 8, Week 16 and Week 20
Population: All randomized participants who took at least one dose of study drug with both baseline and endpoint antibody measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2605541 | Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 8 (Period I) from positive to negative | 3.3 percentage of participants |
| LY2605541 | Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 16 (Period II) from positive to negative | 1.8 percentage of participants |
| LY2605541 | Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 8 (Period I) from negative to positive | 8.3 percentage of participants |
| LY2605541 | Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 20 (follow up) from negative to positive | 14.8 percentage of participants |
| LY2605541 | Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 16 (Period II) from negative to positive | 12.5 percentage of participants |
| LY2605541 | Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 20 (follow up) from positive to negative | 1.9 percentage of participants |
| Glargine | Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 16 (Period II) from negative to positive | 7.4 percentage of participants |
| Glargine | Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 8 (Period I) from negative to positive | 3.3 percentage of participants |
| Glargine | Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 8 (Period I) from positive to negative | 5.0 percentage of participants |
| Glargine | Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 20 (follow up) from positive to negative | 3.8 percentage of participants |
| Glargine | Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 16 (Period II) from positive to negative | 7.4 percentage of participants |
| Glargine | Percentage of Participants With Antibody Status Change From Baseline to Week 8, Week 16 and Week 20 | Week 20 (follow up) from negative to positive | 11.5 percentage of participants |
Secondary
Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 8 Endpoint of Period I
HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time frame: Week 8 (Period I)
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2605541 | Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 8 Endpoint of Period I | HbA1c <7.0% | 43.1 percentage of participants |
| LY2605541 | Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 8 Endpoint of Period I | HbA1c ≤6.5% | 24.6 percentage of participants |
| Glargine | Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 8 Endpoint of Period I | HbA1c <7.0% | 33.3 percentage of participants |
| Glargine | Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 8 Endpoint of Period I | HbA1c ≤6.5% | 13.3 percentage of participants |
p-value: 0.276Fisher Exact
p-value: 0.119Fisher Exact
Secondary
Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 8 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment (Period I)
HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 millimole/Liter (mmol/L) (≤70 milligram/deciliter \[mg/dL\]) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]).
Time frame: Week 8 (Period I)
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2605541 | Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 8 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment (Period I) | HbA1c <7.0% | 1.5 percentage of participants |
| LY2605541 | Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 8 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment (Period I) | HbA1c ≤6.5% | 0 percentage of participants |
| Glargine | Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 8 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment (Period I) | HbA1c <7.0% | 1.7 percentage of participants |
| Glargine | Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 8 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment (Period I) | HbA1c ≤6.5% | 0 percentage of participants |
Secondary
Percentage of Participants With Hypoglycemia Baseline Through Week 8
Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 millimole per Liter (mmol/L) (≤70 milligram per deciliter \[mg/dL\]) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\].
Time frame: Baseline through Week 8 of each treatment period
Population: All randomized participants who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2605541 | Percentage of Participants With Hypoglycemia Baseline Through Week 8 | 92.7 percentage of participants |
| Glargine | Percentage of Participants With Hypoglycemia Baseline Through Week 8 | 90.0 percentage of participants |
Secondary
Pharmacokinetics - Drug (LY2605541) Concentration at Steady State (Css) at Week 8 Endpoint
The drug (LY2605541) concentration at steady state (Css) is calculated from the clearance (Liter/hour) and the final dose of the participants. Clearance was estimated using population-based approaches.
Time frame: Week 8 of each treatment period
Population: Participants who took at least one dose of study drug and had measurements at Week 8.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Pharmacokinetics - Drug (LY2605541) Concentration at Steady State (Css) at Week 8 Endpoint | 2873 picomoles per liter (pMol/L) | Geometric Coefficient of Variation 54.9 |
Secondary
Rate of Hypoglycemia Per 30 Days Baseline Through Week 8
Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]. Hypoglycemia rate per 30 days is calculated as the number of hypoglycemia/number of days at risk\*30.
Time frame: Baseline through Week 8 of each treatment period
Population: All randomized participants who took at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Rate of Hypoglycemia Per 30 Days Baseline Through Week 8 | 8.74 number of hypoglycemia episodes/30 days | Standard Deviation 7.7 |
| Glargine | Rate of Hypoglycemia Per 30 Days Baseline Through Week 8 | 7.36 number of hypoglycemia episodes/30 days | Standard Deviation 6.8 |
p-value: 0.037Negative Binomial Model