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| ID | Type | Description | Link |
|---|---|---|---|
| I2R-MC-BIAX | Other Identifier | Eli Lilly and Company |
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The primary purpose of participation in this study is to compare the safety and efficacy of different dosing schedules of LY2605541 and how different dosing schedules of LY2605541 affect Hemoglobin A1c (HbA1c). Participants will be treated for up to 36 weeks with LY2605541 (one 12-week Lead-in period and two 12-week Randomization periods) and will participate in a total of 42 weeks of total study enrollment, including a 2-week Screening period and a 4-week Follow-up period.
This study involved a comparison of LY2605541 regimens, each administered with bolus insulin lispro. Eligible participants were switched to a fixed evening LY2605541dosing regimen at the beginning of the 12-week lead-in period. LY2605541 was administered SQ once-daily using a prefilled insulin device. The LY2605541dose was adjusted using a dosing algorithm adapted from Bartley and Bolli (Bartley et al. 2008, Bolli et al. 2009) based on the participant's blood glucose (BG) values and documented hypoglycemia during the previous week. Participants not already receiving insulin lispro for prandial dosing were switched to insulin lispro at the beginning of the 12-week lead-in period. Adjustments to insulin lispro doses were based on the insulin dosing algorithms adapted from Riddle and Bergenstal (Riddle et al. 2003, Bergenstal et al. 2008). At the time of randomization, participants were randomized to begin either the fixed evening dosing regimen or the variable time dosing regimen. Each participant was crossed over to the alternate regimen after 12 weeks. The insulin device (prefilled pen) remained the same throughout the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LY2605541 Fixed Time Dosing | Experimental | Participant-specific dose of LY2605541 administered subcutaneously (SQ) at approximately the same time every evening for 12 weeks in the Lead-in Period and in Randomization Period 1 or Randomization Period 2. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on self-monitored blood glucose (SMBG). Target glucose values were as follows: Preprandial and bedtime BG between 71 and 130 milligrams/deciliter (mg/dL) Insulin adjustment and glucose correction between 71 and 100 mg/dL. |
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| LY2605541 Variable Time Dosing | Experimental | Participant-specific dose of LY2605541 administered SQ on a variable time schedule (8- and 40-hour dosing intervals) for 12 weeks in Randomization Period 1 or Randomization Period 2. Dosing schedules were to remain approximately the same throughout the 12 weeks. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on SMBG. Target glucose values were as follows: Preprandial and bedtime BG between 71 and 130 mg/dL Insulin adjustment and glucose correction between 71 and 100 mg/dL. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY2605541 | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Hemoglobin A1c (HbA1c) at 12 Weeks | HbA1c is a test that measures a person's average blood glucose level over the past 2 to 3 months. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis including the following fixed effects: treatment, period, sequence, baseline HbA1c (last nonmissing value at or before randomization), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | At 12 Week in Each Randomization Period |
| Measure | Description | Time Frame |
|---|---|---|
| 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events | Total hypoglycemic events (HE) include any event based on a blood glucose <=70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]), with or without signs/symptoms of hypoglycemia or an event associated with signs/symptoms of hypoglycemia but without a glucose measurement. Nocturnal HE include any total HE that occurred between bedtime and waking. Group Means are presented and were calculated from negative binomial regression models (number of episodes = treatment + period + treatment sequence + baseline HbA1c [<=8.0% or >8.0%], with log [exposure in days/30] as an offset variable). Group Mean (LS mean) is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Concord | California | 94520 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36542287 | Derived | Qu Y, White RD, Ruberg SJ. Accurate Collection of Reasons for Treatment Discontinuation to Better Define Estimands in Clinical Trials. Ther Innov Regul Sci. 2023 May;57(3):521-528. doi: 10.1007/s43441-022-00491-0. Epub 2022 Dec 21. |
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Participants completed a 12 week (wk) Lead-in Period during which insulin peglispro was administered at fixed time in the evening. Participants were then randomized to a fixed evening dose regimen or a variable time dose regimen for 12 wks (Randomization Period 1); after 12 wks, they crossed over to the alternate regimen (Randomization Period 2).
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| ID | Title | Description |
|---|---|---|
| FG000 | LY2605541 Fixed Time Dosing (All Participants) | Lead-in Period: Participant-specific dose of LY2605541 administered subcutaneously (SQ) at approximately the same time every evening for 12 weeks. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on self-monitored blood glucose (SMBG). Target glucose values were as follows: Preprandial and bedtime BG between 71 and 130 milligrams/deciliter (mg/dL) Insulin adjustment and glucose correction between 71 and 100 mg/dL. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Lead-in Period |
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| Insulin Lispro |
| Drug |
All participants will be administering insulin lispro SQ as their pre-meal insulin during the course of the trial. |
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| Baseline (Day 1) of Randomization Period through 24 Weeks (12 weeks in each Randomization Period) |
| Percentage of Participants With Total and Nocturnal Hypoglycemic Events | Total HE include any event based on a blood glucose <=70 mg/dL (3.9 mmol/L), with or without signs/symptoms of hypoglycemia or an event associated with signs/symptoms of hypoglycemia but without a glucose measurement. Nocturnal HE include any total HE that occurred between bedtime and waking. The percentage of participants was calculated by dividing the number of participants with hypoglycemic episodes by the total number of participants analyzed, multiplied by 100. | Baseline (Day 1) of Randomization Period through 24 weeks (12 weeks in each Randomization Period) |
| Fasting Blood Glucose (FBG) Measured by Self-Monitored Blood Glucose | FBG was measured by self-monitored blood glucose (SMBG). LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline FBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | At 12 Weeks in Each Randomization Period |
| Intra-Participant Variability of FBG at 12 Weeks | FBG was measured by SMBG. Between-day glucose variability is measured by the standard deviation of FBG. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline intra-participant variability in FBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | At 12 Weeks in Each Randomization Period |
| Fasting Serum Glucose (FSG) at 12 Weeks | LS means for FSG (obtained from clinical laboratory tests) were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline FSG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | At 12 Weeks in Each Randomization Period |
| Change From Randomization to 12 Weeks in 9-Point SMBG | SMBG measurements were taken at 9 time points: pre-morning meal, 2 hours post-morning meal, pre-midday meal, 2 hours post-midday meal, pre-evening meal, 2 hours post-evening meal, bedtime, at approximately 0300 hours, and the subsequent morning prior to the morning meal. SMBG measures were assessed at Weeks 0, 4, 8, and 12 within each Randomization Period. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline SMBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Randomization, 12 Weeks in Each Randomization Period |
| Self-Monitored Blood Glucose (SMBG) at 12 Weeks | SMBG measurements were taken at 9 time points: pre-morning meal, 2 hours post-morning meal, pre-midday meal, 2 hours post-midday meal, pre-evening meal, 2 hours post-evening meal, bedtime, at approximately 0300 hours, and the subsequent morning prior to the morning meal. SMBG measures were assessed at Weeks 0, 4, 8, and 12 within each Randomization Period. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline SMBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | At 12 Week in Each Randomization Period |
| Intra-participant Variability in SMBG at 12 Weeks | A summary of glucose variability (intra-participant variability) as measured by the average of between-day standard deviations of individual SMBG time points. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline intra-participant variability in SMBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | At 12 Week in Each Randomization Period |
| Change From Randomization to 12 Weeks in Body Weight | LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline body weight (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Randomization, 12 Weeks in Each Randomization Period |
| Change From Day 1 of Lead-In Period to 36 Weeks in Body Weight | LS means were calculated using MMRM analysis, including visit and baseline weight (last non-missing value at or before the beginning of Lead-in Period) as covariates. | Day 1 of Lead-In Period, 36 Weeks |
| Change From Randomization to 12 Weeks in HbA1c | LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline HbA1c (last nonmissing value at or before randomization), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Randomization, 12 Weeks in Each Randomization Period |
| Participants With Treatment-Emergent Anti-LY2605541 Antibody Response | The number of participants with a treatment emergent anti-LY2605541 antibody response (TEAR) is presented. Positive TEAR was defined as change from baseline to post-baseline in the anti-LY2605541 antibody level either from 1) undetectable to detectable or from 2) detectable to the value with at least 130% relative increase from baseline. | Day 1 of Lead-in Period through 36 Weeks |
| Basal, Bolus, and Total Insulin Doses at 12 Weeks | LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline insulin dose (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | At 12 Weeks in Each Randomization Period |
| Proportion of Bolus to Total Insulin Doses at 12 Weeks | Proportion of bolus to total insulin dose is presented, where LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline proportion of bolus to total insulin dose (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | At 12 Weeks in Each Randomization Period |
| 0300-Hour Blood Glucose to Fasting Blood Glucose Excursion | Excursion results were calculated by subtracting the 0300 hours glucose value from the next day pre-morning glucose value within a single SMBG profile. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline 0300-hour to next day pre-breakfast excursion (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | At 12 Week in Each Randomization Period |
| Change From Day 1 of Lead-in to 36 Weeks in Triglycerides, Total Cholesterol, Low-Density Lipoprotein Cholesterol (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) | LS means were calculated using MMRM analysis including visit and baseline lipid level (last nonmissing value at or before the beginning of Lead-in) as covariates. | Day 1 of Lead-In Period, 36 Weeks |
| Percentage of Participants With HbA1c <7.0% and ≤6.5% at 12 Weeks | The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. | At 12 Weeks in Each Randomization Period |
| United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Escondido | California | 92026 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Fresno | California | 93720 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Tustin | California | 92780 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Aurora | Colorado | 80045 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Roswell | Georgia | 30076 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Idaho Falls | Idaho | 83404 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Crystal Lake | Illinois | 60012 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Des Moines | Iowa | 50314 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Topeka | Kansas | 66606 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lexington | Kentucky | 40503 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Oklahoma City | Oklahoma | 73104 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Greer | South Carolina | 29651 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Chattanooga | Tennessee | 37411 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Austin | Texas | 78731 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Dallas | Texas | 75230 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Round Rock | Texas | 78681 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Bayamón | 00961 | Puerto Rico |
| FG001 | LY2605541 Fixed Time Dosing, LY2605541 Variable Time Dosing | Randomization Period 1: Participant-specific dose of LY2605541 administered SQ at approximately the same time every evening for 12 weeks. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Randomization Period 2: Participant-specific dose of LY2605541 administered SQ on a variable schedule (8- and 40-hour dosing intervals) for 12 weeks. Participants were dosed in the morning on Monday, Wednesday, and Friday and in the evening on Tuesday, Thursday, Saturday, and Sunday. Dosing schedules were to remain approximately the same throughout the 12 weeks. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on SMBG. Target glucose values were as follows: Preprandial and bedtime BG between 71 and 130 mg/dL Insulin adjustment and glucose correction between 71 and 100 mg/dL. |
| FG002 | LY2605541 Variable Time Dosing, LY2605541 Fixed Time Dosing | Randomization Period 1: Participant-specific dose of LY2605541 administered SQ on a variable schedule (8- and 40-hour dosing intervals) for 12 weeks. Participants were dosed in the morning on Monday, Wednesday, and Friday and in the evening on Tuesday, Thursday, Saturday, and Sunday. Dosing schedules were to remain approximately the same throughout the 12 weeks. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Randomization Period 2: Participant-specific dose of LY2605541 administered SQ at approximately the same time every evening for 12 weeks. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on SMBG. Target glucose values were as follows: Preprandial and bedtime BG between 71 and 130 mg/dL Insulin adjustment and glucose correction between 71 and 100 mg/dL. |
| COMPLETED |
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| NOT COMPLETED |
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| Randomization Period 1 |
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| Randomization Period 2 |
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All enrolled participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Enrolled Participants | Participants entered a 12-week Lead-in Period where they received fixed time of dose of LY2605541 with bolus insulin lispro. Participants were then randomized to either a fixed time of dose or a variable time of dose regimen for 12 weeks administered with bolus insulin lispro; after 12 weeks, they crossed over to the alternate regimen. LY2605541 dose was adjusted using a dosing algorithm based on the participant's BG values and documented hypoglycemia during the previous week. Insulin dose were determined by insulin algorithms based on SMBG. Fixed time of dose: Participant-specific dose of LY2605541 administered SQ at approximately the same time every evening for 12 weeks administered with bolus insulin lispro. Variable time of dose: Participant-specific dose of LY2605541 administered SQ on a variable schedule (8- and 40-hour dosing intervals) for 12 weeks. Dosing schedules were to remain approximately the same throughout the 12 weeks administered with bolus insulin lispro. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants | No |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
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| Race (NIH/OMB) | Count of Participants | Participants | No |
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| Region of Enrollment | Count of Participants | Participants | No |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Hemoglobin A1c (HbA1c) at 12 Weeks | HbA1c is a test that measures a person's average blood glucose level over the past 2 to 3 months. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis including the following fixed effects: treatment, period, sequence, baseline HbA1c (last nonmissing value at or before randomization), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable HbA1c data. | Posted | Least Squares Mean | Standard Error | percentage of HbA1c | At 12 Week in Each Randomization Period |
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| Secondary | 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events | Total hypoglycemic events (HE) include any event based on a blood glucose <=70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]), with or without signs/symptoms of hypoglycemia or an event associated with signs/symptoms of hypoglycemia but without a glucose measurement. Nocturnal HE include any total HE that occurred between bedtime and waking. Group Means are presented and were calculated from negative binomial regression models (number of episodes = treatment + period + treatment sequence + baseline HbA1c [<=8.0% or >8.0%], with log [exposure in days/30] as an offset variable). Group Mean (LS mean) is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable HE data during Randomization Periods. | Posted | Least Squares Mean | Standard Error | events/participant/30 days | Baseline (Day 1) of Randomization Period through 24 Weeks (12 weeks in each Randomization Period) |
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| Secondary | Percentage of Participants With Total and Nocturnal Hypoglycemic Events | Total HE include any event based on a blood glucose <=70 mg/dL (3.9 mmol/L), with or without signs/symptoms of hypoglycemia or an event associated with signs/symptoms of hypoglycemia but without a glucose measurement. Nocturnal HE include any total HE that occurred between bedtime and waking. The percentage of participants was calculated by dividing the number of participants with hypoglycemic episodes by the total number of participants analyzed, multiplied by 100. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable HE data during Randomization Periods | Posted | Number | percentage of participants | Baseline (Day 1) of Randomization Period through 24 weeks (12 weeks in each Randomization Period) |
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| Secondary | Fasting Blood Glucose (FBG) Measured by Self-Monitored Blood Glucose | FBG was measured by self-monitored blood glucose (SMBG). LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline FBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable FBG data. | Posted | Least Squares Mean | Standard Error | mg/dL | At 12 Weeks in Each Randomization Period |
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| Secondary | Intra-Participant Variability of FBG at 12 Weeks | FBG was measured by SMBG. Between-day glucose variability is measured by the standard deviation of FBG. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline intra-participant variability in FBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable FBG data. | Posted | Least Squares Mean | Standard Error | mg/dL | At 12 Weeks in Each Randomization Period |
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| Secondary | Fasting Serum Glucose (FSG) at 12 Weeks | LS means for FSG (obtained from clinical laboratory tests) were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline FSG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable FSG data. | Posted | Least Squares Mean | Standard Error | mg/dL | At 12 Weeks in Each Randomization Period |
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| Secondary | Change From Randomization to 12 Weeks in 9-Point SMBG | SMBG measurements were taken at 9 time points: pre-morning meal, 2 hours post-morning meal, pre-midday meal, 2 hours post-midday meal, pre-evening meal, 2 hours post-evening meal, bedtime, at approximately 0300 hours, and the subsequent morning prior to the morning meal. SMBG measures were assessed at Weeks 0, 4, 8, and 12 within each Randomization Period. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline SMBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable SMBG data. | Posted | Least Squares Mean | Standard Error | mg/dL | Randomization, 12 Weeks in Each Randomization Period |
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| Secondary | Self-Monitored Blood Glucose (SMBG) at 12 Weeks | SMBG measurements were taken at 9 time points: pre-morning meal, 2 hours post-morning meal, pre-midday meal, 2 hours post-midday meal, pre-evening meal, 2 hours post-evening meal, bedtime, at approximately 0300 hours, and the subsequent morning prior to the morning meal. SMBG measures were assessed at Weeks 0, 4, 8, and 12 within each Randomization Period. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline SMBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable SMBG data. | Posted | Least Squares Mean | Standard Error | mg/dL | At 12 Week in Each Randomization Period |
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| Secondary | Intra-participant Variability in SMBG at 12 Weeks | A summary of glucose variability (intra-participant variability) as measured by the average of between-day standard deviations of individual SMBG time points. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline intra-participant variability in SMBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable SMBG variability data. | Posted | Least Squares Mean | Standard Error | mg/dL | At 12 Week in Each Randomization Period |
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| Secondary | Change From Randomization to 12 Weeks in Body Weight | LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline body weight (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable body weight data. | Posted | Least Squares Mean | Standard Error | kilograms (kg) | Randomization, 12 Weeks in Each Randomization Period |
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| Secondary | Change From Day 1 of Lead-In Period to 36 Weeks in Body Weight | LS means were calculated using MMRM analysis, including visit and baseline weight (last non-missing value at or before the beginning of Lead-in Period) as covariates. | All enrolled participants who completed the first visit of the Lead-in Period, received at least 1 dose of study drug, and had evaluable body weight data. | Posted | Least Squares Mean | Standard Error | kg | Day 1 of Lead-In Period, 36 Weeks |
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| Secondary | Change From Randomization to 12 Weeks in HbA1c | LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline HbA1c (last nonmissing value at or before randomization), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable HbA1c data. | Posted | Least Squares Mean | Standard Error | percentage of HbA1c | Randomization, 12 Weeks in Each Randomization Period |
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| Secondary | Participants With Treatment-Emergent Anti-LY2605541 Antibody Response | The number of participants with a treatment emergent anti-LY2605541 antibody response (TEAR) is presented. Positive TEAR was defined as change from baseline to post-baseline in the anti-LY2605541 antibody level either from 1) undetectable to detectable or from 2) detectable to the value with at least 130% relative increase from baseline. | Participants who completed the first visit of the Lead-in Period, received at least 1 dose of study drug, and had evaluable anti-LY2605541 antibody data. | Posted | Number | participants | Day 1 of Lead-in Period through 36 Weeks |
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| Secondary | Basal, Bolus, and Total Insulin Doses at 12 Weeks | LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline insulin dose (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable insulin dose data. | Posted | Least Squares Mean | Standard Error | units/kg/day | At 12 Weeks in Each Randomization Period |
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| Secondary | Proportion of Bolus to Total Insulin Doses at 12 Weeks | Proportion of bolus to total insulin dose is presented, where LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline proportion of bolus to total insulin dose (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable bolus to total insulin dose data. | Posted | Least Squares Mean | Standard Error | units/day | At 12 Weeks in Each Randomization Period |
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| Secondary | 0300-Hour Blood Glucose to Fasting Blood Glucose Excursion | Excursion results were calculated by subtracting the 0300 hours glucose value from the next day pre-morning glucose value within a single SMBG profile. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline 0300-hour to next day pre-breakfast excursion (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable SMBG excursion data. | Posted | Least Squares Mean | Standard Error | mg/dL | At 12 Week in Each Randomization Period |
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| Secondary | Change From Day 1 of Lead-in to 36 Weeks in Triglycerides, Total Cholesterol, Low-Density Lipoprotein Cholesterol (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) | LS means were calculated using MMRM analysis including visit and baseline lipid level (last nonmissing value at or before the beginning of Lead-in) as covariates. | All enrolled participants who completed the first visit of the Lead-in Period, received at least 1 dose of study drug, and had evaluable lipid data. | Posted | Least Squares Mean | Standard Error | mg/dL | Day 1 of Lead-In Period, 36 Weeks |
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| Secondary | Percentage of Participants With HbA1c <7.0% and ≤6.5% at 12 Weeks | The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. | Participants who were randomized, received at least 1 dose of study drug after randomization, and had evaluable HbA1c data. | Posted | Number | percentage of participants | At 12 Weeks in Each Randomization Period |
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Not provided
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LY2605541 (All Participants) | All participants who received at least 1 dose of LY2605541 during the Lead-In Period, Randomization Period 1, and Randomization Period 2. | 30 | 212 | 166 | 212 | ||
| EG001 | LY2605541 Fixed Time Dosing, LY2605541 Variable Time Dosing | Randomization Period 1: Participant-specific dose of LY2605541 administered SQ at approximately the same time every evening for 12 weeks. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Randomization Period 2: Participant-specific dose of LY2605541 administered SQ on a variable schedule (8- and 40-hour dosing intervals) for 12 weeks. Participants were dosed in the morning on Monday, Wednesday, and Friday and in the evening on Tuesday, Thursday, Saturday, and Sunday. Dosing schedules were to remain approximately the same throughout the 12 weeks. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on SMBG. Target glucose values were as follows: Preprandial and bedtime BG between 71 and 130 mg/dL Insulin adjustment and glucose correction between 71 and 100 mg/dL. | 11 | 177 | 83 | 177 | ||
| EG002 | LY2605541 Variable Time Dosing, LY2605541 Fixed Time Dosing | Randomization Period 1: Participant-specific dose of LY2605541 administered SQ on a variable schedule (8- and 40-hour dosing intervals) for 12 weeks. Participants were dosed in the morning on Monday, Wednesday, and Friday and in the evening on Tuesday, Thursday, Saturday, and Sunday. Dosing schedules were to remain approximately the same throughout the 12 weeks. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Randomization Period 2: Participant-specific dose of LY2605541 administered SQ at approximately the same time every evening for 12 weeks. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on SMBG. Target glucose values were as follows: Preprandial and bedtime BG between 71 and 130 mg/dL Insulin adjustment and glucose correction between 71 and 100 mg/dL. | 7 | 180 | 88 | 180 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Impaired gastric emptying | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Convulsion | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypoglycaemic seizure | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Conjunctivitis | Eye disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Food poisoning | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Injection site swelling | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Local swelling | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Corneal abrasion | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Liver function test abnormal | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Lipoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Lipohypertrophy | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C587357 | LY2605541 |
| C000621851 | basal insulin peglispro |
| D061268 | Insulin Lispro |
| ID | Term |
|---|---|
| D061266 | Insulin, Short-Acting |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
| Adverse Event |
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| Lost to Follow-up |
|
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
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| White |
|
| More than one race |
|
| Unknown or Not Reported |
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