A Study in Adults With Type 1 Diabetes (ELEMENT 1)

This study has been completed.
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01421147
First received: August 19, 2011
Last updated: October 3, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to compare the effectiveness and safety of LY2963016 versus Lantus when taken once daily in combination with insulin lispro before meals three times a day.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Drug: LY2963016
Drug: Lantus
Drug: Insulin Lispro
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Open-label Comparison of a Long-Acting Basal Insulin Analog LY2963016 to Lantus in Combination With Mealtime Insulin Lispro in Adult Patients With Type 1 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change From Baseline up to 24 Weeks in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, Endpoint (up to 24 weeks) ] [ Designated as safety issue: No ]
    HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline HbA1c, treatment and time of basal insulin injection (daytime, evening/bedtime) and country.


Secondary Outcome Measures:
  • Change From Baseline in Insulin Antibody Levels [ Time Frame: Baseline, 6 weeks and 12 weeks and Endpoints (up to 24 weeks and up to 52 weeks) ] [ Designated as safety issue: Yes ]
    Blood samples are collected from participants and percentage of insulin antibody binding was measured to determine the insulin antibody levels. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.

  • Change From Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, 6 weeks and 12 weeks and 24 weeks and 36 weeks and 52 weeks and Endpoint (up to 52 weeks) ] [ Designated as safety issue: No ]
    HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline HbA1c, treatment and time of basal insulin injection (daytime, evening/bedtime) and country.

  • 7-Point Self-Monitored Blood Glucose (SMBG) Profiles [ Time Frame: Baseline and Endpoints [up to 24 weeks (wk) and up to 52 weeks] ] [ Designated as safety issue: No ]
    7-point SMBG measurements are completed at the following timepoints: Morning (AM) Pre-Meal, AM Post-Prandial (PP), Midday (MD) Pre-Meal, MD PP, Evening (EV) Pre-Meal, Bed Time and 0300 hours. PP glucose is measured 2 hours (hrs) after the start of the meal. Values for the 7-point SMBG profiles were averaged over the three 7-point SMBG profiles during 2-week period prior to each visit. If only 1 of the 3 days of data was collected, then the value of the 1 day was used. If only 2 of the 3 days of data were collected, then the average of the 2 days was used. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.

  • Glycemic Variability of Fasting Blood Glucose [ Time Frame: Baseline and Endpoints (up to 24 weeks and up 52 weeks) ] [ Designated as safety issue: No ]
    Glycemic variability is the intra-participant standard deviation (SD) value of fasting blood glucose as measured by the actual morning premeal blood glucose value from the 7-point self-monitoring blood glucose (SMBG) profiles. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.

  • Change From Baseline in Body Weight [ Time Frame: Baseline, 6 weeks and 12 weeks and 18 weeks and Endpoints (up to 24 weeks and up to 52 weeks) ] [ Designated as safety issue: No ]
    Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.

  • Adult Low Blood Sugar Survey (ALBSS) [ Time Frame: Baseline and 24 weeks and Endpoint (up to 52 weeks) ] [ Designated as safety issue: No ]
    ALBSS contains 33 items, with each item scored on a 5-point response scale: 0 (never) to 4 (almost always). Items are categorized in 2 domains: Behavior (or avoidance) Items 1 to 15 and Worry (or affect) Items 16 to 33. Behavior Total Score (TS) range is 0 to 60 and Worry TS range is 0 to 72. Higher scores on "Behavior" items (related to avoidance of hypoglycemia) reflect greater awareness and/or effort of the participant to prevent low blood sugar. Higher scores on "Worry" items (related to worries about low blood sugar and its consequences) reflect greater participant concern about having low blood sugar. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.

  • Insulin Treatment Satisfaction Questionnaire (ITSQ) [ Time Frame: Baseline and 24 weeks and Endpoint (up to 52 weeks) ] [ Designated as safety issue: No ]
    ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. Items measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother), with lower scores reflecting better outcomes. Items divided into 5 domains: Inconvenience of Regimen [(IR) 5 items: scores range 5-35], Lifestyle Flexibility [(LF) 3 items: scores range 3-21], Glycemic Control [(GC) 3 items: scores range 3-21], Hypoglycemic Control [(HC) 5 items: scores range 5-35], Insulin Delivery Device [(IDD) 6 items: scores range 6-42]. ITSQ Total Overall Scores range from 22-154. Data presented are the transformed score on a scale of 0-100, where transformed score=100×[(7-raw score)/6]. Higher scores indicate better treatment satisfaction. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.

  • Insulin Dose Per Body Weight (U/kg) (Total and by Component [Basal and Bolus (Lispro)]) [ Time Frame: Endpoints [up to 24 weeks (wk) and up to 52 weeks] ] [ Designated as safety issue: No ]
    Total daily insulin dose was adjusted for body weight [units of insulin/kilogram/day (U/kg/day)]. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.

  • Insulin Dose - Units [Total and by Component [Basal and Bolus (Lispro)]) [ Time Frame: Endpoints [up to 24 weeks (wk) and up to 52 weeks] ] [ Designated as safety issue: No ]
    Units of insulin taken daily were presented. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.

  • Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5% [ Time Frame: Baseline and 6 weeks and 12 weeks and 24 weeks and 36 weeks and 52 weeks and Endpoints (up to 24 weeks and up to 52 weeks) ] [ Designated as safety issue: No ]
    HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. The percentage of participants with Hemoglobin A1c (HbA1c) <7.0% or HbA1c ≤6.5% is calculated as the number of participants with an HbA1c level of the cut-off value (<7.0% or ≤6.5%) divided by the number of participants treated, then multiplied by 100.

  • Incidence of Hypoglycemic Events [ Time Frame: Baseline through 24 weeks (wk) and 52 weeks ] [ Designated as safety issue: Yes ]
    Incidence of hypoglycemic events is defined as the number of hypoglycemic events. A hypoglycemic event is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has a blood glucose (BG) concentration of ≤ 70 milligrams/deciliter [mg/dL (3.9 millimoles/liter (mmol/L)], even if it was not associated with signs, symptoms, or treatment consistent with current guidelines [American Diabetes Association (ADA) 2005]. Severe hypoglycemia is defined as a hypoglycemic event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions (these episodes may be associated with sufficient neuroglycopenia to induce seizure or coma; also, BG measurements may not be available during such an event). Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking.

  • Rate Per 30 Days of Hypoglycemic Events [ Time Frame: Baseline through 24 weeks (wk) and 52 weeks ] [ Designated as safety issue: Yes ]
    The rate of hypoglycemic events per 30 days is defined as the total number of events between visits divided by the actual number of days between visits, and then multiplied by 30 days. A hypoglycemic event is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose (BG) concentration of ≤ 70 milligrams/deciliter [mg/dL (3.9 millimoles/liter (mmol/L)], even if it was not associated with signs, symptoms, or treatment consistent with current guidelines (ADA 2005). Severe hypoglycemia is defined as a hypoglycemic event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions (these episodes may be associated with sufficient neuroglycopenia to induce seizure or coma; also, BG measurements may not be available during such an event). Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking.


Enrollment: 536
Study Start Date: August 2011
Study Completion Date: April 2013
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2963016 + Insulin Lispro
LY2963016 titrated based on blood glucose readings, administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro. Insulin lispro titrated based on blood glucose readings, administered subcutaneously, three times a day for 52 weeks.
Drug: LY2963016
Administered subcutaneously
Drug: Insulin Lispro
Administered subcutaneously
Active Comparator: Lantus + Insulin Lispro
Lantus titrated based on blood glucose readings, administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro. Insulin lispro titrated based on blood glucose readings, administered subcutaneously, three times a day for 52 weeks.
Drug: Lantus
Administered subcutaneously
Drug: Insulin Lispro
Administered subcutaneously

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have type 1 diabetes mellitus based on the disease diagnostic criteria [World Health Organization (WHO) Classification]
  • Have duration of diabetes greater than or equal to one year
  • Have Hemoglobin A1c (HbA1c) less than or equal to 11.0%
  • On basal-bolus insulin therapy for at least 1 year [basal insulin must be once daily (QD) injection of human insulin isophane suspension (NPH), Lantus, or detemir and combined with mealtime injections of human regular insulin, or insulin analog lispro, aspart or glulisine]
  • Have a body mass index (BMI) of less than or equal to 35 kilograms/square meter (kg/m²)

Exclusion Criteria:

  • Have had more than one episode of severe low blood sugar (defined as needing someone else to help because you had very low blood sugar) within the 6 months before entering the study
  • Have had more than one episode of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes leading to hospitalization within the 6 months before entering the study
  • Have known hypersensitivity or allergy to any of the study insulins (insulin glargine or insulin lispro) or to excipients of the study insulins
  • Have significant renal, cardiac, gastrointestinal or liver disease
  • Have active cancer or cancer within the past 5 years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01421147

  Show 52 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Boehringer Ingelheim
Investigators
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01421147     History of Changes
Other Study ID Numbers: 13712, I4L-MC-ABEB, 2011-000829-73
Study First Received: August 19, 2011
Results First Received: October 3, 2014
Last Updated: October 3, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Japan: Pharmaceuticals and Medical Devices Agency
Mexico: Federal Commission for Protection Against Health Risks
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
Russia: Ministry of Health of the Russian Federation

Keywords provided by Eli Lilly and Company:
Diabetes
Type 1 Diabetes
Diabetes Mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin
Insulin Lispro
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 16, 2014