A Study in Participants With Type 2 Diabetes Mellitus
- Conditions
- Diabetes Mellitus, Type 2
- Interventions
- Registration Number
- NCT01468987
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of this study is:
* To compare blood glucose (blood sugar) control on LY2605541 with insulin glargine after 26 weeks of treatment.
* To compare the rate of night time hypoglycemia (low blood glucose) on LY2605541 with insulin glargine during 26 weeks of treatment.
* To compare the number of participants on LY2605541 reaching blood glucose targets without hypoglycemia episodes at night to those taking insulin glargine after 26 weeks of treatment.
* To compare the rate of hypoglycemia over a 24-hour period on LY2605541 with insulin glargine during 26 weeks of treatment.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1369
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LY2605541 + Insulin Lispro LY2605541 Participant-specific dose of LY2605541 will be administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro will be administered SC for preprandial and supplemental doses for 26 weeks. Insulin Glargine + Insulin Lispro Insulin Glargine Participant-specific dose of Insulin Glargine will be administered subcutaneously (SC) once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro will be administered SC for preprandial (pre-meal) and supplemental doses for 26 weeks. Insulin Glargine + Insulin Lispro Insulin Lispro Participant-specific dose of Insulin Glargine will be administered subcutaneously (SC) once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro will be administered SC for preprandial (pre-meal) and supplemental doses for 26 weeks. LY2605541 + Insulin Lispro Insulin Lispro Participant-specific dose of LY2605541 will be administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro will be administered SC for preprandial and supplemental doses for 26 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline in Hemoglobin A1c (HbA1c) at 26 Weeks 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, low-density lipoprotein cholesterol \[LDL-C, \<100 milligrams per deciliter (mg/dL) and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Total Hypoglycemia Episodes Baseline through 26 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). 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.
Basal, Bolus, and Total Insulin Dose by Weight at 26 Weeks 26 weeks Basal insulin dose, short-acting bolus insulin dose (each meal and overall), and total insulin dose were calculated based on the dose during the last 7 days prior to the post-treatment visit or last 3 days prior to the randomization visit. LS means were calculated using a constrained Longitudinal Data Analysis (cLDA) model adjusting for indicator variables of each treatment group at each post-baseline visit and stratification variables (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and baseline number of insulin injections \[1, 2, or ≥3\]).
HbA1c at 26 Weeks 26 weeks HbA1c is a test that measures a participant's average blood glucose level over the past 2 to 3 months. LS means were calculated using MMRM adjusting for stratification factors (country, LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), treatment, visit, treatment, visit-by-treatment interaction, and baseline HbA1c.
Total Hypoglycemia Rates (Adjusted for 30 Days) Baseline through 26 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 \[mmol/L\]). Group mean rates of total hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline total hypoglycemia rate, 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 With HbA1c <7.0% and ≤6.5% at 26 Weeks up to 26 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.
Fasting Serum Glucose (FSG) From Laboratory at 26 Weeks 26 weeks 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 number of insulin injections at baseline \[1, 2, or ≥3\]), treatment, visit, treatment-by-visit interaction, and baseline FSG.
Fasting Blood Glucose (FBG) (by SMBG) Intra-participant Variability at 26 Weeks 26 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 (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), treatment, visit, treatment-by-visit interaction, and baseline FBG variability.
Number of Participants With Change in Anti-LY2605541 Antibodies From Baseline to 26 Weeks Baseline through 26 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.
Nocturnal Hypoglycemia Rates (Adjusted for 30 Days) Baseline through 26 weeks Hypoglycemic episodes are defined as events which are associated with reported signs and symptoms of hypoglycemia and/or a documented BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. Group mean rates of nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline nocturnal hypoglycemia rate, 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 With Nocturnal Hypoglycemia Episodes Baseline through 26 weeks Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia and/or a BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with nocturnal hypoglycemic episodes by the total number of participants analyzed, multiplied by 100.
Body Weight Change From Baseline to 26 Weeks Baseline, 26 weeks 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 number of insulin injections at baseline \[1, 2, or ≥3\]), treatment, visit, treatment-by-visit interaction, and baseline body weight as fixed effects, and participant as a random effect.
Self-Monitored Blood Glucose (SMBG) 9-point Profiles at 26 Weeks 26 weeks 9-point SMBG profiles were obtained over 2 nonconsecutive days within the week prior to Weeks 0, 4, 12, and 26. 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. 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 number of insulin injections at baseline \[1, 2, or ≥3\]), visit, treatment, visit-by-treatment interaction, and baseline BG values.
Lipid Profile at 26 Weeks 26 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 (baseline HbA1c \[≤8.5% and \>8.5%\], country, LDL-C \[\<100 mg/dL and ≥100 mg/dL\], except for the LDL-C outcome variable\], number of insulin injections at baseline \[1, 2, or ≥3\]), visit, treatment, visit-by-treatment interaction, and baseline value of corresponding lipid outcome variable.
EuroQoL-5D (EQ-5D) at 26 Weeks up to 26 weeks The EQ-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 three 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 ANCOVA adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, and baseline number of insulin injections \[1, 2, or ≥ 3\]), and baseline EQ-5D score.
Percentage of Participants With HbA1c <7.0% Without Nocturnal Hypoglycemia at 26 Weeks up to 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 concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. 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.
0300-hour Blood Glucose to FBG Excursion at 26 Weeks 26 weeks Results of a 0300-hour to pre-morning meal (FBG) excursion are presented (only SMBG profiles with both 0300 hours and the next day pre-morning measurements are included for the calculation of such excursion). LS means were calculated using MMRM adjusting for stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), treatment, visit, treatment-by-visit interaction, and baseline excursion.
Insulin Treatment Satisfaction Questionnaire (ITSQ) at 26 Weeks up to 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 higher scores indicate better treatment satisfaction. LS means were calculated using an analysis of covariance (ANCOVA) model with treatment and stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, and baseline number of insulin injections \[1, 2, or ≥3\]) as fixed effects and baseline value of the ITSQ scores as a covariate.
Low Blood Sugar Survey (LBSS) at 26 Weeks 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 MMRM including stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline number of insulin injections \[1, 2, or ≥3\]), visit, treatment, visit-by-treatment interaction, and baseline LBSS score.
Rapid Assessment of Physical Activity (RAPA) at 26 Weeks up to 26 weeks The RAPA questionnaire assesses the level and intensity of physical activity of adult participants. It contains 2 subscales: RAPA 1 (Aerobic) and RAPA 2 (Strength and Flexibility). RAPA 1 contains 7 questions regarding the participant's amount and intensity of physical activity, allowing each participant's aerobic activity level to be categorized as sedentary, underactive, light activities, light activity, regular underactive, or active. RAPA 2 contains 2 questions regarding participants' physical activities that increase strength and improve flexibility. Each participant's strength and flexibility activity level is then categorized as neither strength nor flexibility activity, either strength or flexibility activity (not both), both strength and flexibility activity. The percentage of participants in each RAPA 1/2 category is presented and was calculated by dividing the number of participants in each RAPA 1/2 category by the total number of participants analyzed, multiplied by 100.
Trial Locations
- Locations (1)
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.
🇬🇧Guildford, Surrey, United Kingdom