April 19, 2012
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April 20, 2012
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March 17, 2018
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April 20, 2018
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April 20, 2018
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May 2012
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May 2013 (Final data collection date for primary outcome measure)
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Change From Baseline to 26-week Endpoint in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, 26 weeks ] 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 using mixed model repeated measures (MMRM) adjusting for stratification factors (country, baseline low-density lipoprotein cholesterol [LDL-C, <100 milligrams per deciliter (mg/dL) and ≥100 mg/dL], and sulfonylurea (SU) or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.
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Change From Baseline to 26-week Endpoint in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, 26 weeks ]
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Complete list of historical versions of study NCT01582451 on ClinicalTrials.gov Archive Site
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- Change From Baseline to 52 Weeks in HbA1c [ Time Frame: Baseline, 52 weeks ]
LS means were calculated using MMRM adjusting for stratification factors (country, baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.
- Rate of Total and Nocturnal Hypoglycemia Events (Adjusted by 30 Days) [ Time Frame: Baseline through 26 weeks and Baseline through 52 weeks ]
Hypoglycemic episodes are defined as events which are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 millimoles per liter [mmol/L]). A nocturnal hypoglycemic event 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 (number of episodes = treatment + baseline hypoglycemia rate + baseline SU or meglitinide use, with log [exposure in days/30] as an offset variable). Group Mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.
- Percentage of Participants That Have Total and Nocturnal Hypoglycemic Events [ Time Frame: Baseline through 26 weeks and Baseline through 52 weeks ]
Hypoglycemic episodes are defined as events which are associated with reported signs and symptoms of hypoglycemia and/or documented BG concentrations of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event 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.
- Percentage of Participants With HbA1c Equal to or Less Than (≤) 6.5% and Less Than (<) 7.0% [ Time Frame: 26 and 52 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.
- Percentage of Participants With HbA1c <7.0% and Without Nocturnal Hypoglycemia [ Time Frame: 26 and 52 weeks ]
Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia and/or a documented blood glucose concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking. The percentage of participants was calculated by dividing the number of participants with HbA1c <7.0% without nocturnal hypoglycemia by the total number of participants analyzed, multiplied by 100.
- Fasting Serum Glucose (FSG) (by Laboratory) [ Time Frame: 26 and 52 weeks ]
LS means were calculated using MMRM adjusting for stratification factors (country, baseline HbA1c [≤8.0% and >8.0%], baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline FSG.
- Fasting Blood Glucose (FBG) (by Self Monitoring) [ Time Frame: 26 and 52 weeks ]
LS means were calculated using MMRM adjusting for stratification factors (country, baseline HbA1c [≤8.0% and >8.0%], baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline FBG.
- Intra-participant Variability in Fasting Blood Glucose (FBG) [ Time Frame: 26 and 52 weeks ]
FBG was measured by self-monitored blood glucose (SMBG). Between-day glucose variability is measured by the standard deviation of FBG. LS means were calculated using MMRM adjusting for the stratification factors (country, baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and SU or meglitinide use), treatment, visit, treatment-by-visit interaction, and baseline FBG intra-participant variability.
- 6-point Self-monitored Blood Glucose (SMBG) [ Time Frame: 26 and 52 weeks ]
SMBG measurements were taken at 6 time points (pre-morning meal [fasting], pre-midday meal, pre-evening meal, bedtime, approximately 0300 hours, and pre-morning meal [fasting] on the next day) and were performed on 2 non-consecutive days in the week prior to next office visit. LS means were calculated using MMRM adjusting for stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, LDL-C [<100 mg/dL and ≥100 mg/dL], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline BG values.
- HbA1c [ Time Frame: 26 and 52 weeks ]
LS means were calculated using MMRM adjusting for stratification factors (country, baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.
- Insulin Dose Per Kilogram of Body Weight [ Time Frame: 26 and 52 weeks ]
Daily basal insulin dose is presented. LS means were calculated using MMRM adjusting for the stratification factors (country, baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and SU or meglitinide use), treatment, visit, treatment-by-visit interaction, and baseline insulin dose.
- Number of Insulin Dose Adjustments to Steady-state [ Time Frame: Baseline through 26 weeks ]
The number of dose adjustments required to reach a steady dose is presented. LS means were calculated from negative binomial regression models, where the number of dose adjustments = treatment + stratification factors (country, baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and SU or meglitinide use).
- European Quality of Life - 5 Dimension (EuroQol-5D) Score [ Time Frame: 26 weeks ]
The EuroQol-5D 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 3-level scale of 1-3 (no problem, some problems, and extreme problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United States population-based algorithm. Scores range from -0.11 to 1.0, where a score of 1.0 indicates perfect health. LS means were calculated using an analysis of covariance (ANCOVA) model adjusting for treatment, stratification factors (country, baseline HbA1c [≤8.5% and >8.5%], and SU or meglitinide use), and baseline EuroQol-5D score.
- Insulin Treatment Satisfaction Questionnaire (ITSQ) Score [ Time Frame: 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 overall score on a scale of 0-100, where a higher score indicate better treatment satisfaction. LS means were calculated using ANCOVA with treatment and stratification factors (country, baseline HbA1c [≤8.5% and >8.5%], and SU or meglitinide use) as fixed effects and baseline value of the ITSQ score as a covariate.
- Adult Low Blood Sugar Survey (LBSS) Score [ Time Frame: 26 weeks ]
LBSS (also referenced as Hypoglycemia Fear Survey - II [HFS-II]) is a 33-item questionnaire that measures 1) behaviors to avoid hypoglycemia and its negative consequences (15 items) and 2) worries about hypoglycemia and its negative consequences (18 items). Responses are made on a 5-point Likert scale where 0 = Never and 4 = Always. Total score is the sum of all items (range 0-132). Higher total scores reflect greater fear of hypoglycemia. LS means were calculated using ANCOVA with treatment and stratification factors (country, baseline HbA1c [≤8.5% and >8.5%], and SU or meglitinide use) as fixed effects and baseline value of the LBSS score as a covariate.
- Change From Baseline in Body Weight [ Time Frame: Baseline, 26 weeks, 52 weeks ]
LS means were calculated using MMRM adjusting for stratification factors (country, baseline HbA1c [≤8.5% and >8.5%], LDL-C [<100 mg/dL and ≥100 mg/dL, except for the LDL-C outcome variable], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline body weight.
- Change From Baseline in Lipid Profile [ Time Frame: Baseline, 26 weeks, 52 weeks ]
Concentrations of cholesterol, high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides are summarized. LS means were calculated using MMRM adjusting for stratification factors (country, baseline HbA1c [≤8.5% and >8.5%], LDL-C [<100 mg/dL and ≥100 mg/dL, except for the LDL-C outcome variable], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline value of corresponding lipid outcome variable.
- Number of Participants With Change in Anti-LY2605541 Antibodies [ Time Frame: Baseline through 52 weeks ]
The number of participants with a treatment-emergent anti-LY2605541 antibody response (TEAR) is summarized. TEAR is defined as change from baseline to post-baseline in the anti-LY2605541 antibody level either from undetectable to detectable, or from detectable to the value with at least 130% relative increase from baseline.
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- Rate of Total and Nocturnal Hypoglycemia Events (Adjusted by 30 Days) [ Time Frame: Baseline to 26 weeks and Baseline to 52 weeks ]
- Percentage of Participants With HbA1c Equal to or Less Than (≤) 6.5% and Less Than (<) 7.0% [ Time Frame: 26 and 52 weeks ]
- Fasting serum glucose (FSG) (by laboratory) and fasting blood glucose (FBG) (by self monitoring) [ Time Frame: 26 and 52 weeks ]
- 6-point self-monitored blood glucose (SMBG) [ Time Frame: 26 and 52 weeks ]
- Change From Baseline in Body Weight [ Time Frame: Baseline, 26 weeks, 52 weeks ]
- HbA1c [ Time Frame: 26 and 52 weeks ]
- Insulin Dose Per Kilogram of Body Weight [ Time Frame: 26 and 52 weeks ]
- Number of Insulin Dose Adjustments to Steady-state [ Time Frame: Baseline to 26 weeks ]
- European Quality of Life - 5 Dimension (EuroQol-5D) score [ Time Frame: 26 weeks ]
- Insulin Treatment Satisfaction Questionnaire (ITSQ) Score [ Time Frame: 26 weeks ]
- Adult Low Blood Sugar Survey (LBSS) Score [ Time Frame: 26 weeks ]
- Change From Baseline in Lipid Profile [ Time Frame: Baseline, 26 weeks, 52 weeks ]
- Change in anti-LY2605541 antibodies [ Time Frame: Baseline, 26 weeks, 52 weeks ]
- Intra-participant Variability in Fasting Blood Glucose (FBG) [ Time Frame: 26 weeks and 52 weeks ]
- Percentage of Participants That Have Total and Nocturnal Hypoglycemic Events [ Time Frame: Baseline to 26 weeks and Baseline to 52 weeks ]
- Percentage of Participants With HbA1c <7.0% and Without Nocturnal Hypoglycemia [ Time Frame: 26 and 52 weeks ]
- Change From Baseline to 52 Weeks in HbA1c [ Time Frame: Baseline, 52 weeks ]
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Not Provided
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Not Provided
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A Study of LY2605541 in Participants With Type 2 Diabetes Mellitus |
A Comparison of LY2605541 Versus Insulin Glargine Alone or in Combination With Pre-study Oral Antihyperglycemic Medications in Patients With Type 2 Diabetes Mellitus Previously Treated With Basal Insulin: An Open-Label, Randomized Study The IMAGINE 5 Study |
The purpose of this study is to compare LY2605541 and insulin glargine using the following measures after participants have been treated for 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 blood sugar episodes at night
- The rate of low blood sugar episodes reported over a 24-hour period
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Not Provided |
Interventional |
Phase 3 |
Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
Diabetes Mellitus, Type 2 |
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- Experimental: LY2605541
Administered by subcutaneous (SQ) injection once daily at bedtime. Initial dose based on dose of prestudy basal insulin and adjusted based on fasting blood glucose (FBG). LY2605541 will be given alone or in combination with up to 3 pre-study oral antihyperglycemic medications (OAMs) whose use is not excluded in combination with insulin. Treatment may last up to 52 weeks.
Intervention: Drug: LY2605541
- Active Comparator: Insulin glargine
Administered by SQ injection once daily at bedtime. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG. Insulin glargine will be used alone or in combination with up to 3 pre-study OAMs whose use is not excluded in combination with insulin. Treatment may last up to 52 weeks.
Intervention: Drug: Insulin glargine
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- Sanyal A, Cusi K, Hartman ML, Zhang S, Bastyr EJ 3rd, Bue-Valleskey JM, Chang AM, Haupt A, Jacober SJ, Konrad RJ, Zhang Q, Hoogwerf BJ. Cytokeratin-18 and enhanced liver fibrosis scores in type 1 and type 2 diabetes and effects of two different insulins. J Investig Med. 2018 Mar;66(3):661-668. doi: 10.1136/jim-2017-000609. Epub 2017 Nov 21.
- Orchard TJ, Cariou B, Connelly MA, Otvos JD, Zhang S, Antalis CJ, Ivanyi T, Hoogwerf BJ. The effects of basal insulin peglispro vs. insulin glargine on lipoprotein particles by NMR and liver fat content by MRI in patients with diabetes. Cardiovasc Diabetol. 2017 Jun 6;16(1):73. doi: 10.1186/s12933-017-0555-1.
- Cusi K, Sanyal AJ, Zhang S, Hartman ML, Bue-Valleskey JM, Hoogwerf BJ, Haupt A. Non-alcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes and type 2 diabetes. Diabetes Obes Metab. 2017 Nov;19(11):1630-1634. doi: 10.1111/dom.12973. Epub 2017 Jun 22.
- Buse JB, Rodbard HW, Trescoli Serrano C, Luo J, Ivanyi T, Bue-Valleskey J, Hartman ML, Carey MA, Chang AM; IMAGINE 5 Investigators. Randomized Clinical Trial Comparing Basal Insulin Peglispro and Insulin Glargine in Patients With Type 2 Diabetes Previously Treated With Basal Insulin: IMAGINE 5. Diabetes Care. 2016 Jan;39(1):92-100. doi: 10.2337/dc15-1531. Epub 2015 Nov 17.
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Completed |
466 |
426 |
December 2013 |
May 2013 (Final data collection date for primary outcome measure) |
Inclusion Criteria:
- Have had type 2 diabetes mellitus for at least 1 year
- Have been receiving basal insulin (neutral protamine Hagedorn [NPH], detemir, or glargine) and a stable dose of 0 to 3 oral antihyperglycemic medications (OAMs) used as specified in the local prescribing information for at least 90 days prior to screening. At least 1 of the OAMs must be dosed at, or above, half the maximum daily dose allowed by local regulations or at the maximally tolerated dose
- Have a hemoglobin A1c (HbA1c) less than or equal to 9.0% 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 who are not breastfeeding, have a negative pregnancy test at screening and randomization, do not plan to become pregnant during the study, and 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:
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Senior) |
No |
Contact information is only displayed when the study is recruiting subjects |
Czechia, Germany, Greece, Israel, Puerto Rico, Romania, Russian Federation, Spain, United States |
Czech Republic |
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NCT01582451 |
14703 I2R-MC-BIDJ ( Other Identifier: Eli Lilly and Company ) |
Yes |
Not Provided |
Not Provided |
Eli Lilly and Company |
Eli Lilly and Company |
Not Provided |
Study Director: |
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 |
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Eli Lilly and Company |
March 2018 |