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Trial record 6 of 7 for:    LY2963016

A Study in Adults With Type 2 Diabetes (ELEMENT 2)

This study has been completed.
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01421459
First received: August 19, 2011
Last updated: October 3, 2014
Last verified: October 2014
  Purpose

The main purpose of this study is to compare the effectiveness and safety of LY2963016 versus Lantus in controlling blood sugar levels in combination with two or more oral diabetes medications.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: LY2963016
Drug: Lantus
Drug: OAMs
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Double-Blind Comparison of a Long-Acting Basal Insulin Analog LY2963016 to Lantus in Adult Patients With Type 2 Diabetes Mellitus: The ELEMENT 2 Study

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. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection and treatment.


Secondary Outcome Measures:
  • Change From Baseline in Insulin Antibody Levels [ Time Frame: Baseline and 4 weeks and 12 weeks and Endpoint (24 weeks and up to 24 weeks) ] [ Designated as safety issue: Yes ]
    Blood samples are collected from participants and percentage of insulin antibody binding measured. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline of response and treatment.

  • Change From Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline and 4 weeks and 8 weeks and 12 weeks and 16 weeks and 20 weeks and 24 weeks ] [ Designated as safety issue: No ]
    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection and treatment.

  • 7-Point Self-Monitored Blood Glucose (SMBG) Profiles [ Time Frame: Baseline and Endpoint [up to 24 weeks (wk)] ] [ Designated as safety issue: No ]
    Seven-point SMBG are completed at the following timepoints: Morning (AM) Pre-Meal, Morning (AM) Post-Prandial (PP), Midday (MD) Pre-Meal, Midday PP, Evening (EV) Pre-Meal, Bed Time and 0300 hours. PP glucose is measured 2 hours (hrs) after the start of the meal. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment.

  • Glycemic Variability of Fasting Blood Glucose [ Time Frame: Baseline and Endpoint (up to 24 weeks) ] [ Designated as safety issue: No ]
    Glycemic variability is measured by the intra-participant standard deviation (SD) value of fasting blood glucose as measured by the actual morning pre-meal blood glucose value from the 7-point self-monitoring blood glucose [SMBG] profiles. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment.

  • Change From Baseline in Body Weight [ Time Frame: Baseline and 4 weeks (wk) and 8 wk and 12 wk and 16 wk and 20 wk and 24 wk and Endpoint (up to 24 wk) ] [ Designated as safety issue: No ]
    Change from baseline in body weight. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment.

  • Adult Low Blood Sugar Survey (ALBSS) [ Time Frame: 4 weeks (wk) and 12 wk and Endpoint (up to 24 wk) ] [ 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 range is 0 to 60 and Worry Total Score 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. The ALBSS Total Scores (Worry and Behavior item scores combined) range is 0 to 132. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment.

  • Insulin Treatment Satisfaction Questionnaire (ITSQ) [ Time Frame: 4 weeks (wk) and 12 wk and Endpoint (EP) (up to 24 wk) ] [ 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 divided into 5 domains of satisfaction: 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]. Items measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother), with lower scores reflecting better outcomes. ITSQ Total Overall Scores range from 22-154. Raw domain scores are transformed on a scale of 0-100, where transformed domain score=100×[(7-raw domain score)/6]. Higher scores indicate better treatment satisfaction. Least Squares (LS) mean are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment.

  • Insulin Dose Per Body Weight (U/kg) Per Day [ Time Frame: Endpoint (up to 24 weeks) ] [ Designated as safety issue: No ]
    Insulin dose in units (U) per body weight in kilograms (kg) per day. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment.

  • Insulin Dose (Units) [ Time Frame: Endpoint (up to 24 weeks) ] [ Designated as safety issue: No ]
    Units of insulin taken daily. Least Square (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1C, country, sulfonylurea use, time of basal insulin injection and treatment.

  • Percentage of Participants With HbA1c <7 % and HbA1c ≤6.5% [ Time Frame: Baseline and 4 weeks and 8 weeks and 12 weeks and 16 weeks and 20 weeks and 24 weeks and Endpoint (up to 24 weeks) ] [ Designated as safety issue: No ]
    Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time.

  • Incidence of Hypoglycemic Events [ Time Frame: Baseline and Endpoint (up to 24 weeks) ] [ Designated as safety issue: Yes ]
    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) even if it was not associated with signs, symptoms, or treatment consistent with current American Diabetes Association (ADA: 2005) guidelines. 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, Endpoint (up to 24 weeks) ] [ Designated as safety issue: Yes ]
    The rate of hypoglycemic events per 30 days between two visits is defined as the total number of events between the visits divided by the actual number of days between the visits, and then multiplied by 30 days. A hypoglycemic event is defined as any time a participant has a blood glucose (BG) level of ≤70 milligrams per deciliter (mg/dL) even if the event was not associated with signs, symptoms, or treatment consistent with current guidelines (American Diabetes Association 2005). Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking. Severe hypoglycemia is defined as a hypoglycemic event requiring assistance of another person to actively administer carbohydrates, glucagons, or other resuscitative actions. Severe Hypoglycemic events may or may not have a reported BG ≤70 mg/dL. These events may be associated with sufficient neuroglycopenia to induce seizure or coma.


Other Outcome Measures:
  • Percentage of Participants With Detectable Insulin Antibody Levels [ Time Frame: Baseline and 4 weeks and 12 weeks and 24 weeks and Endpoint (up to 24 weeks) and Baseline to 24 weeks (Overall) ] [ Designated as safety issue: Yes ]
  • Percentage of Participants With Treatment Emergent Antibody Response (TEAR) [ Time Frame: 4 weeks and 12 weeks and 24 weeks and Endpoint (up to 24 weeks) and Baseline to 24 weeks (Overall) ] [ Designated as safety issue: Yes ]
    TEAR is defined as an absolute increase of at least 1% in insulin antibody levels (measured in % binding) and at least 30% relative increase from Baseline for participants who are insulin antibody-positive at Baseline, or turning from insulin antibody-negative status at Baseline to antibody-positive during the course of the study following treatment with study drug.


Enrollment: 759
Study Start Date: September 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2963016 + OAMs
LY2963016 titrated based on blood glucose readings, administered subcutaneously, once daily in combination with at least 2 oral antihyperglycemic medications (OAMs) [alpha glucosidase inhibitors (AGI), dipeptidyl peptidases intravenous (DPP-IV), meglitinide (MEG), metformin (MET), sulfonylurea (SU), and thiazolidinedione (TZD)] administered per standard of care for 24 weeks
Drug: LY2963016
Administered subcutaneously
Drug: OAMs
Administered orally
Active Comparator: Lantus + OAMs
Lantus titrated based on blood glucose readings, administered subcutaneously, once daily in combination with at least 2 OAMs (AGI, DPP-IV, MEG, MET, SU, and TZD) administered per standard of care for 24 weeks
Drug: Lantus
Administered subcutaneously
Drug: OAMs
Administered orally

  Eligibility

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

Inclusion Criteria:

  • Have Type 2 Diabetes Mellitus based on the disease diagnostic criteria World Health Organization (WHO) classification
  • Have been taking at least 2 types of oral diabetes medications for at least 12 weeks prior to entering the study
  • Have a Hemoglobin A1c value greater than or equal to 7.0 percent and less than or equal to 11.0 percent if insulin naive If previously on Lantus, then Hemoglobin A1c must be less than or equal to 11.0 percent
  • Have a body mass index of less than or equal to 45 kilogram per meter squared (kg/m^2)

Exclusion Criteria:

  • Have significant liver, cardiac or gastrointestinal disease
  • Have active cancer or have had cancer within the past 5 years (with the exception of basal cell carcinoma or carcinoma in situ)
  • Have an excessive resistance to insulin or hypersensitivity to Lantus
  • 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 taken any other insulin other than Lantus within the past 30 days
  • Taking any other diabetes medicines that are not allowed in the study or not approved to be taken with insulin
  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: NCT01421459

  Show 62 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: NCT01421459     History of Changes
Other Study ID Numbers: 13713, I4L-MC-ABEC, 2011-000828-15
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
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Committee for the Protection of Personnes
France: Conseil National de l'Ordre des Médecins
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
Korea: Food and Drug Administration
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
Slovak Republic: Ethics Committee
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Taiwan : Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Diabetes
Type 2 Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on November 25, 2014