Diabetes Mellitus, Type 2
Conditions
Brief summary
The purpose of this study is to compare LY2605541 and human insulin isophane suspension (NPH) using the following measures for participants treated for up to 26 weeks: * Change in participants' overall blood sugar control * The rate of night time low blood sugar episodes * The number of participants that reach blood sugar targets without low night time blood sugar episodes * The total number of low blood sugar episodes reported
Interventions
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have had type 2 diabetes mellitus for at least 1 year, not treated with insulin * Have been receiving 2 or more OAMs for at least 3 months prior to the study * Have a hemoglobin A1c (HbA1c) of 7.0% to 11.0%, inclusive, at screening * Have a body mass index (BMI) less than or equal to 45.0 kilograms per square meter (kg/m\^2) * Women of childbearing potential are not breastfeeding, have a negative pregnancy test at screening and randomization, do not plan to become pregnant during the study, have practiced reliable birth control for at least 6 weeks prior to screening and will continue to do so during the study and until 2 weeks after the last dose of study drug
Exclusion criteria
* Have used insulin therapy in the past 2 years (except for use during pregnancy or for short term use for acute conditions) * Have been treated with glucagon-like peptide-1 (GLP-1) receptor agonist, rosiglitazone, pramlintide, or weight-loss medication within 3 months before screening * For participants on OAMs: have any restrictions for cardiac, renal, and hepatic diseases in the local product regulations * Are taking, or have taken within the 90 days before screening, prescription or over-the-counter medications to promote weight loss * Have had any episodes of severe hypoglycemia, diabetic ketoacidosis, or hyperosmolar state/coma within 6 months prior to screening * Have cardiac disease with functional status that is New York Heart Association Class III or IV * Have a history of renal transplantation, or are currently receiving renal dialysis or have serum creatinine greater than or equal to 2 milligrams per deciliter (mg/dL) \[177 millimoles per liter (mmol/L)\] * Have obvious clinical signs or symptoms of liver disease \[excluding nonalcoholic fatty liver disease (NAFLD)\], acute or chronic hepatitis, nonalcoholic steatohepatitis (NASH), or elevated liver enzyme measurements * Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the measurement of HbA1c * Have active or untreated cancer, have been in remission from clinically significant cancer(other than basal cell or squamous cell skin cancer) for less than 5 years, or are at increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator * Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intranasal, intraocular, and inhaled preparations) or have received such therapy within the 8 weeks immediately preceding screening * Have fasting triglycerides greater than 400 mg/dL (4.5 mmol/L) at screening * Have an irregular sleep/wake cycle (for example, participants who sleep during the day and work during the night) in the investigator's opinion * Are using or have used any of the following lipid-lowering medications: niacin preparations as a lipid-lowering medication and/or bile acid sequestrants within 90 days prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 26 Weeks in Hemoglobin A1c (HbA1c) | Baseline, 26 Weeks | Glycosylated hemoglobin A1 (HbA1c) is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. Least Squares (LS) means were calculated by mixed model repeated measures (MMRM) using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HbA1c ≤6.5% and <7.0% | 26 Weeks | Percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. |
| Fasting Serum Glucose (FSG) (by Laboratory) | 26 Weeks | LS means were calculated from MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), baseline HbA1c strata \[≤8.5% or \>8.5%\]), visit, treatment-by-visit interaction, and baseline value of the response variable as the fixed effects. |
| Fasting Blood Glucose (FBG) (by Self Monitoring) | 26 Weeks | LS means were calculated from MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), baseline HbA1c strata \[≤8.5% or \>8.5%\]), visit, treatment-by-visit interaction, and baseline value of the response variable as the fixed effects. |
| 6-Point Self-Monitored Blood Glucose (SMBG) | 26 Weeks | 6-point SMBG profiles were obtained on 3 nonconsecutive days in the week prior to Weeks 0, 4, 8, 12, 16, and 26. The SMBG measurements were performed while fasting (prior to the morning meal \[breakfast\]), prior to the midday meal (lunch), prior to the evening meal (dinner), at bedtime, at approximately 0300 hours, and the next day fasting (prior to the morning meal). LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), \], baseline HbA1c strata \[≤8.5% or \>8.5%\]), visit, treatment-by-visit interaction, and baseline SMBG at the same time point of the response variable as the fixed effects. |
| Change From Baseline to 26 Weeks in Body Weight | Baseline, 26 Weeks | LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), baseline HbA1c strata \[≤8.5% or \>8.5%\]), visit, treatment-by-visit interaction, and baseline weight as the fixed effects. |
| HbA1c | 26 Weeks | HbA1c is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects. |
| Insulin Dose Per Kilogram (kg) of Body Weight | 26 Weeks | LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), baseline HbA1c strata \[≤8.5% or \>8.5%\]), visit, and treatment-by-visit interaction as the fixed effects. |
| Time to Steady-State (Stable Maximum Dose) | Baseline through 26 Weeks | Steady-state was defined as the first local maximum dose (peak dose value) of LY2605541 or human insulin NPH within the window of -2 to +2 weeks. The median time to steady-state of basal insulin dose estimated from Kaplan-Meier analysis was summarized by treatment. |
| Change From Baseline to 26 Weeks in European Quality of Life - 5 Dimension 3 Levels (EQ-5D-3L) Index | Baseline, 26 Weeks | The EQ-5D-3L is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a three level scale 1-3 (no problem, some problems, and extreme problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United States (US) population-based algorithm. The EQ-5D-3L US based index scores ranged from -0.11 to 1.0 where a score of 1.0 indicates perfect health. LS means were calculated from ANCOVA using treatment, stratification factor (country, baseline sulfonylurea sulfonylureas/meglitinide use \[Yes/No\], baseline HbA1c strata \[≤8.5% or \>8.5%\]) and baseline value of EQ-5D-3Las covariates. |
| Insulin Treatment Satisfaction Questionnaire (ITSQ) Score | 26 Weeks | ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, Insulin Delivery Device. Data presented are the transformed score on a scale of 0-100, higher scores indicate better treatment satisfaction. LS means were calculated using analysis of variance (ANOVA) adjusting for treatment and stratification factors (country, baseline sulfonylureas/meglitinide use \[Yes/No\], baseline HbA1c \[≤8.5% or \>8.5%\]). |
| 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events | Baseline through 26 Weeks | Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of \<=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]). A nocturnal hypoglycemic event is defined as any total hypoglycemia event that occurred between bedtime and waking. Group mean rates of total and nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models with treatment, baseline sulfonylurea/meglitinide use, baseline event rate of the corresponding hypoglycemia as covariates, log (exposure/30 days) as the offset in the model. Group Mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants. |
| Change From Baseline to 26 Weeks in Lipid Profile | Baseline, 26 Weeks; Baseline, End Of Study (EOS) (Up to 30 Weeks) | Lipid profile includes total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. LS means for post-baseline measures were calculated using MMRM with the fixed effects of stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, sulfonylureas/meglitinide use, and LDL-C \[\<100 mg/dL and ≥100 mg/dL\], except for the LDL-C outcome variable), visit, treatment, visit-by-treatment interaction, and baseline value of corresponding lipid outcome variable. LS means for End Of Study measures were calculated using ANCOVA adjusting for stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, sulfonylureas/meglitinide use, and LDL-C \[\<100 mg/dL and ≥100 mg/dL\]except for the LDL-C outcome variable), treatment, and baseline value of corresponding lipid outcome variable. |
| Percentage of Participants With Insulin Antibodies | Baseline to 26 Weeks | The percentage of participants with a positive treatment-emergent anti-LY2605541 antibody response (TEAR) is summarized. TEAR was defined as change from baseline to postbaseline in the anti-LY2605541 antibody level either (1) from undetectable to detectable or (2) from detectable to the value with at least 130% relative increase from baseline. Percentage of participants was calculated by dividing the number of participants with TEAR anytime during the treatment period by the total number of participants analyzed, multiplied by 100. |
| Intra-Participant Variability in FBG by Standard Deviation | 26 Weeks | Glucose variability was assessed by between-day variability as measured by the standard deviation or the coefficient of variation of the FBG of the last 7 days prior to the visit using SMBG. LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\], baseline HbA1c strata \[≤8.5% or \>8.5%\]), visit, treatment-by-visit interaction, and baseline FBG variability as the fixed effects. |
| Intra-Participant Variability in FBG by the Coefficient of Variation | 26 Weeks | Glucose variability was assessed by between-day variability as measured by the standard deviation or the coefficient of variation of the FBG of the last 7 days prior to the visit using SMBG. |
| Percentage of Participants With Total and Nocturnal Hypoglycemic Events | Baseline through 26 Weeks | Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of \<=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]). A nocturnal hypoglycemic event is defined as any total hypoglycemia event that occurred between bedtime and waking. Percentage of participants was calculated by the number of participants with at least one hypoglycemia divided by the total number of participants analyzed, multiplied by 100. |
| Percentage of Participants With HbA1c <7.0% and Without Nocturnal Hypoglycemia | 26 Weeks | Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of \<=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]). A nocturnal hypoglycemic event is defined as any total hypoglycemia event that occurred between bedtime and waking. Percentage of participants was calculated by the number of participants reaching target HbA1c without nocturnal hypoglycemia divided by the total number of participants analyzed, multiplied by 100. |
| Percentage of Participants With Injection Site Reactions | Baseline through 26 Weeks | The percentage of participants with at least one treatment-emergent injection site reaction is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Rate of Severe Hypoglycemic Events | Baseline through 26 Weeks | Hypoglycemic event are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of \<=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]). A severe hypoglycemic event was defined as a hypoglycemic episode requiring assistance of another person to actively administer carbohydrates, glucagon, or other resuscitative actions. The hypoglycemia rate per 100 years during a defined period was calculated by the number of hypoglycemia events within the period divided by the number of days participant at risk within the period\*36525 days. |
| Percentage of Participants With Severe Hypoglycemic Events | Baseline through 26 Weeks | Hypoglycemic event are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of \<=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]). A severe hypoglycemic event was defined as a hypoglycemic episode requiring assistance of another person to actively administer carbohydrates, glucagon, or other resuscitative actions. The percentage of participants with at least one severe hypoglycemia is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change From Baseline to 26 Weeks in European Quality of Life (EQ-5D-3L) - Visual Analog Scales (VAS) Scores | Baseline, 26 Weeks | The EQ-5D-3L is a generic, multidimensional, health-related, quality-of-life instrument. Overall health state score was self-reported using a visual analogue scale (VAS) marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state. |
| Change From Baseline to 26 Weeks in Adult Low Blood Sugar Survey (LBSS) Scores | Baseline, 26 Weeks | Adult LBSS (also referenced as Hypoglycemia Fear Survey - II \[HFS-II\]) contains 33 items, with each item scored on a 5-point response scale: 0 (never) to 4 (always). Items are categorized in 2 domains: Behavior (or avoidance) with 15 items and Worry (or affect) with 18 items. Sum all the items to obtain a total score (range 0-132). Higher total scores reflect greater fear of hypoglycemia. LS means were calculated using analysis of covariance (ANCOVA) adjusting for treatment, stratification factor (country, baseline sulfonylureas/meglitinide use \[Yes/No\]), baseline HbA1c (≤8.5% or \>8.5%), and baseline value of LBSS. |
Countries
Argentina, Canada, Czechia, Germany, Hungary, Mexico, Poland, Puerto Rico, South Korea, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY2605541 Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. | 428 |
| Human Insulin NPH Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal. | 213 |
| Total | 641 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Death | 4 | 0 |
| Overall Study | Lost to Follow-up | 5 | 2 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Protocol Required Discontinuation | 7 | 1 |
| Overall Study | Sponsor Decision | 0 | 3 |
| Overall Study | Withdrawal by Subject | 13 | 2 |
Baseline characteristics
| Characteristic | Total | LY2605541 | Human Insulin NPH |
|---|---|---|---|
| Age, Continuous | 59.17 years STANDARD_DEVIATION 9.87 | 58.86 years STANDARD_DEVIATION 9.76 | 59.79 years STANDARD_DEVIATION 10.1 |
| Body Mass Index (BMI) | 30.88 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 5.4 | 30.80 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 5.57 | 31.04 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 5.03 |
| Duration of Diabetes | 11.05 years STANDARD_DEVIATION 6.65 | 10.87 years STANDARD_DEVIATION 6.46 | 11.40 years STANDARD_DEVIATION 7.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 221 Participants | 148 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 300 Participants | 195 Participants | 105 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 120 Participants | 85 Participants | 35 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 78 Participants | 53 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 36 Participants | 27 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 523 Participants | 345 Participants | 178 Participants |
| Region of Enrollment Argentina | 45 Participants | 31 Participants | 14 Participants |
| Region of Enrollment Canada | 38 Participants | 25 Participants | 13 Participants |
| Region of Enrollment Czechia | 35 Participants | 23 Participants | 12 Participants |
| Region of Enrollment Germany | 45 Participants | 30 Participants | 15 Participants |
| Region of Enrollment Hungary | 35 Participants | 24 Participants | 11 Participants |
| Region of Enrollment Mexico | 32 Participants | 21 Participants | 11 Participants |
| Region of Enrollment Poland | 56 Participants | 37 Participants | 19 Participants |
| Region of Enrollment Puerto Rico | 65 Participants | 46 Participants | 19 Participants |
| Region of Enrollment South Korea | 73 Participants | 50 Participants | 23 Participants |
| Region of Enrollment Spain | 45 Participants | 29 Participants | 16 Participants |
| Region of Enrollment United States | 172 Participants | 112 Participants | 60 Participants |
| Sex: Female, Male Female | 316 Participants | 209 Participants | 107 Participants |
| Sex: Female, Male Male | 325 Participants | 219 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 228 / 427 | 111 / 212 |
| serious Total, serious adverse events | 28 / 427 | 9 / 212 |
Outcome results
Primary
Change From Baseline to 26 Weeks in Hemoglobin A1c (HbA1c)
Glycosylated hemoglobin A1 (HbA1c) is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. Least Squares (LS) means were calculated by mixed model repeated measures (MMRM) using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.
Time frame: Baseline, 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable HbA1c data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Change From Baseline to 26 Weeks in Hemoglobin A1c (HbA1c) | -1.73 percentage of HbA1c | Standard Error 0.04 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in Hemoglobin A1c (HbA1c) | -1.36 percentage of HbA1c | Standard Error 0.06 |
Secondary
30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events
Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of \<=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]). A nocturnal hypoglycemic event is defined as any total hypoglycemia event that occurred between bedtime and waking. Group mean rates of total and nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models with treatment, baseline sulfonylurea/meglitinide use, baseline event rate of the corresponding hypoglycemia as covariates, log (exposure/30 days) as the offset in the model. Group Mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.
Time frame: Baseline through 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable hypoglycemic data at baseline and with at least one post-baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY2605541 | 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events | Nocturnal | 0.31 episodes per participant per 30 days | Standard Error 0.04 |
| LY2605541 | 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events | Total | 1.46 episodes per participant per 30 days | Standard Error 0.09 |
| Human Insulin NPH | 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events | Total | 1.73 episodes per participant per 30 days | Standard Error 0.13 |
| Human Insulin NPH | 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events | Nocturnal | 0.61 episodes per participant per 30 days | Standard Error 0.07 |
Secondary
6-Point Self-Monitored Blood Glucose (SMBG)
6-point SMBG profiles were obtained on 3 nonconsecutive days in the week prior to Weeks 0, 4, 8, 12, 16, and 26. The SMBG measurements were performed while fasting (prior to the morning meal \[breakfast\]), prior to the midday meal (lunch), prior to the evening meal (dinner), at bedtime, at approximately 0300 hours, and the next day fasting (prior to the morning meal). LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), \], baseline HbA1c strata \[≤8.5% or \>8.5%\]), visit, treatment-by-visit interaction, and baseline SMBG at the same time point of the response variable as the fixed effects.
Time frame: 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable blood glucose data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2605541 | 6-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday meal | 123.78 mg/dL | Standard Error 1.75 |
| LY2605541 | 6-Point Self-Monitored Blood Glucose (SMBG) | Bedtime | 144.14 mg/dL | Standard Error 1.96 |
| LY2605541 | 6-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening meal | 130.90 mg/dL | Standard Error 1.75 |
| LY2605541 | 6-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning meal the next day | 110.42 mg/dL | Standard Error 1.18 |
| LY2605541 | 6-Point Self-Monitored Blood Glucose (SMBG) | 0300 hours | 116.35 mg/dL | Standard Error 1.55 |
| LY2605541 | 6-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning meal | 111.22 mg/dL | Standard Error 1.15 |
| Human Insulin NPH | 6-Point Self-Monitored Blood Glucose (SMBG) | Bedtime | 159.17 mg/dL | Standard Error 2.72 |
| Human Insulin NPH | 6-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning meal | 109.56 mg/dL | Standard Error 1.61 |
| Human Insulin NPH | 6-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday meal | 133.77 mg/dL | Standard Error 2.44 |
| Human Insulin NPH | 6-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening meal | 146.99 mg/dL | Standard Error 2.41 |
| Human Insulin NPH | 6-Point Self-Monitored Blood Glucose (SMBG) | 0300 hours | 117.66 mg/dL | Standard Error 2.15 |
| Human Insulin NPH | 6-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning meal the next day | 109.03 mg/dL | Standard Error 1.65 |
Secondary
Change From Baseline to 26 Weeks in Adult Low Blood Sugar Survey (LBSS) Scores
Adult LBSS (also referenced as Hypoglycemia Fear Survey - II \[HFS-II\]) contains 33 items, with each item scored on a 5-point response scale: 0 (never) to 4 (always). Items are categorized in 2 domains: Behavior (or avoidance) with 15 items and Worry (or affect) with 18 items. Sum all the items to obtain a total score (range 0-132). Higher total scores reflect greater fear of hypoglycemia. LS means were calculated using analysis of covariance (ANCOVA) adjusting for treatment, stratification factor (country, baseline sulfonylureas/meglitinide use \[Yes/No\]), baseline HbA1c (≤8.5% or \>8.5%), and baseline value of LBSS.
Time frame: Baseline, 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable LBSS data. Missing endpoints were imputed with the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Change From Baseline to 26 Weeks in Adult Low Blood Sugar Survey (LBSS) Scores | 0.53 units on a scale | Standard Error 0.72 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in Adult Low Blood Sugar Survey (LBSS) Scores | 2.05 units on a scale | Standard Error 1.01 |
Secondary
Change From Baseline to 26 Weeks in Body Weight
LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), baseline HbA1c strata \[≤8.5% or \>8.5%\]), visit, treatment-by-visit interaction, and baseline weight as the fixed effects.
Time frame: Baseline, 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable body weight data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Change From Baseline to 26 Weeks in Body Weight | 2.02 kilograms (kg) | Standard Error 0.16 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in Body Weight | 2.34 kilograms (kg) | Standard Error 0.22 |
Secondary
Change From Baseline to 26 Weeks in European Quality of Life - 5 Dimension 3 Levels (EQ-5D-3L) Index
The EQ-5D-3L is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a three level scale 1-3 (no problem, some problems, and extreme problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United States (US) population-based algorithm. The EQ-5D-3L US based index scores ranged from -0.11 to 1.0 where a score of 1.0 indicates perfect health. LS means were calculated from ANCOVA using treatment, stratification factor (country, baseline sulfonylurea sulfonylureas/meglitinide use \[Yes/No\], baseline HbA1c strata \[≤8.5% or \>8.5%\]) and baseline value of EQ-5D-3Las covariates.
Time frame: Baseline, 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable EQ-5D-3L data. Missing endpoints were imputed with the last observation carried forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Change From Baseline to 26 Weeks in European Quality of Life - 5 Dimension 3 Levels (EQ-5D-3L) Index | 0.02 units on a scale | Standard Error 0.01 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in European Quality of Life - 5 Dimension 3 Levels (EQ-5D-3L) Index | 0.01 units on a scale | Standard Error 0.01 |
Secondary
Change From Baseline to 26 Weeks in European Quality of Life (EQ-5D-3L) - Visual Analog Scales (VAS) Scores
The EQ-5D-3L is a generic, multidimensional, health-related, quality-of-life instrument. Overall health state score was self-reported using a visual analogue scale (VAS) marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state.
Time frame: Baseline, 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable EuroQol-5D-3L data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Change From Baseline to 26 Weeks in European Quality of Life (EQ-5D-3L) - Visual Analog Scales (VAS) Scores | 2.52 units on a scale | Standard Deviation 0.68 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in European Quality of Life (EQ-5D-3L) - Visual Analog Scales (VAS) Scores | 1.41 units on a scale | Standard Deviation 0.95 |
Secondary
Change From Baseline to 26 Weeks in Lipid Profile
Lipid profile includes total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. LS means for post-baseline measures were calculated using MMRM with the fixed effects of stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, sulfonylureas/meglitinide use, and LDL-C \[\<100 mg/dL and ≥100 mg/dL\], except for the LDL-C outcome variable), visit, treatment, visit-by-treatment interaction, and baseline value of corresponding lipid outcome variable. LS means for End Of Study measures were calculated using ANCOVA adjusting for stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, sulfonylureas/meglitinide use, and LDL-C \[\<100 mg/dL and ≥100 mg/dL\]except for the LDL-C outcome variable), treatment, and baseline value of corresponding lipid outcome variable.
Time frame: Baseline, 26 Weeks; Baseline, End Of Study (EOS) (Up to 30 Weeks)
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable lipid data. Missing endpoints for End Of Study measures were imputed with the LOCF method.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2605541 | Change From Baseline to 26 Weeks in Lipid Profile | Total cholesterol, 26 Weeks | 2.08 mg/dL | Standard Error 1.42 |
| LY2605541 | Change From Baseline to 26 Weeks in Lipid Profile | Total cholesterol, End Of Study (Up to 30 Weeks) | -0.12 mg/dL | Standard Error 1.36 |
| LY2605541 | Change From Baseline to 26 Weeks in Lipid Profile | HDL, 26 Weeks | -0.24 mg/dL | Standard Error 0.31 |
| LY2605541 | Change From Baseline to 26 Weeks in Lipid Profile | HDL, End Of Study (Up to 30 Weeks) | 0.53 mg/dL | Standard Error 0.31 |
| LY2605541 | Change From Baseline to 26 Weeks in Lipid Profile | LDL, 26 Weeks | 3.01 mg/dL | Standard Error 1.24 |
| LY2605541 | Change From Baseline to 26 Weeks in Lipid Profile | LDL, End Of Study (Up to 30 Weeks) | 2.54 mg/dL | Standard Error 1.2 |
| LY2605541 | Change From Baseline to 26 Weeks in Lipid Profile | Triglycerides, 26 Weeks | -1.49 mg/dL | Standard Error 4.62 |
| LY2605541 | Change From Baseline to 26 Weeks in Lipid Profile | Triglycerides, End Of Study (Up to 30 Weeks) | -20.34 mg/dL | Standard Error 4.79 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in Lipid Profile | Triglycerides, End Of Study (Up to 30 Weeks) | -0.45 mg/dL | Standard Error 6.74 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in Lipid Profile | Total cholesterol, 26 Weeks | 2.86 mg/dL | Standard Error 2 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in Lipid Profile | LDL, 26 Weeks | 5.90 mg/dL | Standard Error 1.74 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in Lipid Profile | Total cholesterol, End Of Study (Up to 30 Weeks) | 2.94 mg/dL | Standard Error 1.92 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in Lipid Profile | Triglycerides, 26 Weeks | -15.38 mg/dL | Standard Error 6.49 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in Lipid Profile | HDL, 26 Weeks | 0.41 mg/dL | Standard Error 0.44 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in Lipid Profile | LDL, End Of Study (Up to 30 Weeks) | 3.89 mg/dL | Standard Error 1.69 |
| Human Insulin NPH | Change From Baseline to 26 Weeks in Lipid Profile | HDL, End Of Study (Up to 30 Weeks) | 0.40 mg/dL | Standard Error 0.44 |
Secondary
Fasting Blood Glucose (FBG) (by Self Monitoring)
LS means were calculated from MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), baseline HbA1c strata \[≤8.5% or \>8.5%\]), visit, treatment-by-visit interaction, and baseline value of the response variable as the fixed effects.
Time frame: 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable FBG data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Fasting Blood Glucose (FBG) (by Self Monitoring) | 111.37 milligrams per deciliter (mg/dL) | Standard Error 1.15 |
| Human Insulin NPH | Fasting Blood Glucose (FBG) (by Self Monitoring) | 109.75 milligrams per deciliter (mg/dL) | Standard Error 1.6 |
Secondary
Fasting Serum Glucose (FSG) (by Laboratory)
LS means were calculated from MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), baseline HbA1c strata \[≤8.5% or \>8.5%\]), visit, treatment-by-visit interaction, and baseline value of the response variable as the fixed effects.
Time frame: 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable FSG.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Fasting Serum Glucose (FSG) (by Laboratory) | 112.61 milligrams per deciliter (mg/dL) | Standard Error 1.56 |
| Human Insulin NPH | Fasting Serum Glucose (FSG) (by Laboratory) | 118.60 milligrams per deciliter (mg/dL) | Standard Error 2.2 |
Secondary
HbA1c
HbA1c is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.
Time frame: 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable HbA1c data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | HbA1c | 6.76 percentage of HbA1c | Standard Error 0.04 |
| Human Insulin NPH | HbA1c | 7.12 percentage of HbA1c | Standard Error 0.06 |
Secondary
Insulin Dose Per Kilogram (kg) of Body Weight
LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), baseline HbA1c strata \[≤8.5% or \>8.5%\]), visit, and treatment-by-visit interaction as the fixed effects.
Time frame: 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable insulin dose and body weight data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Insulin Dose Per Kilogram (kg) of Body Weight | 0.40 units per kilogram | Standard Error 0.01 |
| Human Insulin NPH | Insulin Dose Per Kilogram (kg) of Body Weight | 0.35 units per kilogram | Standard Error 0.02 |
Secondary
Insulin Treatment Satisfaction Questionnaire (ITSQ) Score
ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, Insulin Delivery Device. Data presented are the transformed score on a scale of 0-100, higher scores indicate better treatment satisfaction. LS means were calculated using analysis of variance (ANOVA) adjusting for treatment and stratification factors (country, baseline sulfonylureas/meglitinide use \[Yes/No\], baseline HbA1c \[≤8.5% or \>8.5%\]).
Time frame: 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable ITSQ data. Missing endpoints were imputed with the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Insulin Treatment Satisfaction Questionnaire (ITSQ) Score | 85.04 units on a scale | Standard Error 0.63 |
| Human Insulin NPH | Insulin Treatment Satisfaction Questionnaire (ITSQ) Score | 83.84 units on a scale | Standard Error 0.89 |
Secondary
Intra-Participant Variability in FBG by Standard Deviation
Glucose variability was assessed by between-day variability as measured by the standard deviation or the coefficient of variation of the FBG of the last 7 days prior to the visit using SMBG. LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\], baseline HbA1c strata \[≤8.5% or \>8.5%\]), visit, treatment-by-visit interaction, and baseline FBG variability as the fixed effects.
Time frame: 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable FBG data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Intra-Participant Variability in FBG by Standard Deviation | 14.44 mg/dL | Standard Deviation 0.5 |
| Human Insulin NPH | Intra-Participant Variability in FBG by Standard Deviation | 19.07 mg/dL | Standard Deviation 0.7 |
Secondary
Intra-Participant Variability in FBG by the Coefficient of Variation
Glucose variability was assessed by between-day variability as measured by the standard deviation or the coefficient of variation of the FBG of the last 7 days prior to the visit using SMBG.
Time frame: 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable FBG data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Intra-Participant Variability in FBG by the Coefficient of Variation | 12.87 mg/dL | Geometric Coefficient of Variation 0.4 |
| Human Insulin NPH | Intra-Participant Variability in FBG by the Coefficient of Variation | 17.05 mg/dL | Geometric Coefficient of Variation 0.56 |
Secondary
Percentage of Participants With HbA1c ≤6.5% and <7.0%
Percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.
Time frame: 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable HbA1c data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2605541 | Percentage of Participants With HbA1c ≤6.5% and <7.0% | HbA1c ≤6.5% | 43.4 Percentage of Participants |
| LY2605541 | Percentage of Participants With HbA1c ≤6.5% and <7.0% | HbA1c <7.0% | 66.3 Percentage of Participants |
| Human Insulin NPH | Percentage of Participants With HbA1c ≤6.5% and <7.0% | HbA1c <7.0% | 44.7 Percentage of Participants |
| Human Insulin NPH | Percentage of Participants With HbA1c ≤6.5% and <7.0% | HbA1c ≤6.5% | 24.1 Percentage of Participants |
Secondary
Percentage of Participants With HbA1c <7.0% and Without Nocturnal Hypoglycemia
Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of \<=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]). A nocturnal hypoglycemic event is defined as any total hypoglycemia event that occurred between bedtime and waking. Percentage of participants was calculated by the number of participants reaching target HbA1c without nocturnal hypoglycemia divided by the total number of participants analyzed, multiplied by 100.
Time frame: 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable HbA1c data and hypoglycemia data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2605541 | Percentage of Participants With HbA1c <7.0% and Without Nocturnal Hypoglycemia | 39.1 percentage of participants |
| Human Insulin NPH | Percentage of Participants With HbA1c <7.0% and Without Nocturnal Hypoglycemia | 12.6 percentage of participants |
Secondary
Percentage of Participants With Injection Site Reactions
The percentage of participants with at least one treatment-emergent injection site reaction is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2605541 | Percentage of Participants With Injection Site Reactions | 0.9 percentage of participants |
| Human Insulin NPH | Percentage of Participants With Injection Site Reactions | 1.4 percentage of participants |
Secondary
Percentage of Participants With Insulin Antibodies
The percentage of participants with a positive treatment-emergent anti-LY2605541 antibody response (TEAR) is summarized. TEAR was defined as change from baseline to postbaseline in the anti-LY2605541 antibody level either (1) from undetectable to detectable or (2) from detectable to the value with at least 130% relative increase from baseline. Percentage of participants was calculated by dividing the number of participants with TEAR anytime during the treatment period by the total number of participants analyzed, multiplied by 100.
Time frame: Baseline to 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable anti-drug (LY2605541) antibodies (ADA) data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2605541 | Percentage of Participants With Insulin Antibodies | 19.7 percentage of participants |
| Human Insulin NPH | Percentage of Participants With Insulin Antibodies | 45.8 percentage of participants |
Secondary
Percentage of Participants With Severe Hypoglycemic Events
Hypoglycemic event are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of \<=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]). A severe hypoglycemic event was defined as a hypoglycemic episode requiring assistance of another person to actively administer carbohydrates, glucagon, or other resuscitative actions. The percentage of participants with at least one severe hypoglycemia is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable hypoglycemic data at baseline and with at least one post-baseline value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2605541 | Percentage of Participants With Severe Hypoglycemic Events | 0.5 percentage of participants |
| Human Insulin NPH | Percentage of Participants With Severe Hypoglycemic Events | 0.0 percentage of participants |
Secondary
Percentage of Participants With Total and Nocturnal Hypoglycemic Events
Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of \<=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]). A nocturnal hypoglycemic event is defined as any total hypoglycemia event that occurred between bedtime and waking. Percentage of participants was calculated by the number of participants with at least one hypoglycemia divided by the total number of participants analyzed, multiplied by 100.
Time frame: Baseline through 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable hypoglycemic data at baseline and with at least one post-baseline value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2605541 | Percentage of Participants With Total and Nocturnal Hypoglycemic Events | Total | 76.7 percentage of participants |
| LY2605541 | Percentage of Participants With Total and Nocturnal Hypoglycemic Events | Nocturnal | 41.6 percentage of participants |
| Human Insulin NPH | Percentage of Participants With Total and Nocturnal Hypoglycemic Events | Total | 83.5 percentage of participants |
| Human Insulin NPH | Percentage of Participants With Total and Nocturnal Hypoglycemic Events | Nocturnal | 67.5 percentage of participants |
Secondary
Rate of Severe Hypoglycemic Events
Hypoglycemic event are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of \<=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]). A severe hypoglycemic event was defined as a hypoglycemic episode requiring assistance of another person to actively administer carbohydrates, glucagon, or other resuscitative actions. The hypoglycemia rate per 100 years during a defined period was calculated by the number of hypoglycemia events within the period divided by the number of days participant at risk within the period\*36525 days.
Time frame: Baseline through 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable hypoglycemic data at baseline and with at least one post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LY2605541 | Rate of Severe Hypoglycemic Events | 1.00 events per 100 participant years | Standard Deviation 0.71 |
| Human Insulin NPH | Rate of Severe Hypoglycemic Events | 0.00 events per 100 participant years | Standard Deviation 0 |
Secondary
Time to Steady-State (Stable Maximum Dose)
Steady-state was defined as the first local maximum dose (peak dose value) of LY2605541 or human insulin NPH within the window of -2 to +2 weeks. The median time to steady-state of basal insulin dose estimated from Kaplan-Meier analysis was summarized by treatment.
Time frame: Baseline through 26 Weeks
Population: Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable steady state data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY2605541 | Time to Steady-State (Stable Maximum Dose) | 7.14 weeks |
| Human Insulin NPH | Time to Steady-State (Stable Maximum Dose) | 5.86 weeks |