The DURABLE Trial: Evaluating the Durability of Starter Insulin Regimens in Patients With Type 2 Diabetes (IOOV)

Official Title: “The Durability of Twice-Daily Insulin Lispro Low Mixture Compared to Once-Daily Insulin Glargine When Added to Existing Oral Therapy in Patients With Type 2 Diabetes and Inadequate Glycemic Control”

This study will compare insulin lispro low mixture [LM] and insulin glargine both in combination with the patient's oral diabetes medicines, for their ability to control blood sugar in patients with type 2 diabetes and compare insulin lispro LM to insulin glargine with regard to the length of time that the overall blood sugar can be controlled.

This study will also determine whether the safety of insulin lispro LM and any side effects that might be associated with it are different from those observed with insulin glargine, both in combination with the patient's oral diabetes medications.

The addendum study (Intensification Addendum) will compare how different insulin treatments work to control blood sugar in patients whose diabetes could not be controlled by either insulin lispro LM or insulin glargine.

Intervention(s) in this Clinical Trial

• Drug: Insulin glargine
  • Subcutaneous injection daily
• Drug: Lispro Low Mix
  • Subcutaneous injection twice daily.
• Drug: Lispro Mid Mix
  • Lispro Mid Mix subcutaneous injection 3 times daily.
• Drug: Lispro
  • Lispro subcutaneous injection 3 times daily.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Insulin glargine
  • Initiation Phase: Insulin glargine for 24 weeks Maintenance: Up to an additional 2 years of insulin glargine if glycosylated hemoglobin (HbA1c) less than or equal to 7.0 at 24 weeks.
• Experimental: Lispro Low Mix
  • Initiation Phase: Lispro Low Mix (LM) for 24 weeks Maintenance Phase: Up to an additional 2 years of Lispro LM if HbA1c less than or equal to 7.0 at 24 weeks.
• Experimental: Lispro Mid Mix prior Lispro Low Mix addendum
  • Following Lispro LM Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Lispro Mid Mix for 24 weeks in the Intensification Addendum Phase.
• Experimental: Lispro Low Mix prior Glargine addendum
  • Following Insulin Glargine Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Lispro Low Mix for 24 weeks in the Intensification Addendum Phase
• Active Comparator: Basal bolus prior Lispro Low Mix addendum
  • Following Lispro LM Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Basal Bolus therapy (combination of insulin glargine and lispro) for 24 weeks in the Intensification Addendum Phase.
• Active Comparator: Basal bolus prior Glargine addendum
  • Following Insulin Glargine Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Basal Bolus therapy (combination of insulin glargine and lispro) for 24 weeks in the Intensification Addendum Phase.

Primary Measures

• INITIATION: 24-Week Endpoint Glycosylated Hemoglobin (HbA1c)
  • Time Frame: Endpoint (Initiation: Week 24)
    Safety Issue?: No
• MAINTENANCE: Duration of Time HbA1c Maintained at Goal by Initiation Regimen (Insulin Glargine or Lispro Low Mix)
  • Time Frame: Endpoint (Last Observation Carried Forward [LOCF]) (Maintenance: up to 2.5 years)
    Safety Issue?: No
• ADDENDUM: 24-Week Endpoint HbA1c
  • Time Frame: Endpoint (Addendum) (24 weeks: Week 48)
    Safety Issue?: No

Secondary Measures

• INITIATION: Change in HbA1c From Baseline to 24 Weeks
  • Time Frame: Baseline (Initiation) to Endpoint (LOCF, Week 24)
    Safety Issue?: No
• INITIATION: Percentage of Participants With HbA1c < or = 7.0%, HbA1c <7.0%, and HbA1c < or = 6.5% at Endpoint
  • Time Frame: Endpoint (Initiation: Week 24)
    Safety Issue?: No
• INITIATION: HbA1c
  • Time Frame: Baseline (Initiation), Week 12, Week 24, Endpoint (LOCF)
    Safety Issue?: No
• INITIATION: 7-point Self-monitored Plasma Glucose (SMPG) Profiles and Postprandial Excursions
  • Time Frame: Endpoint (LOCF) (Initiation: Week 24)
    Safety Issue?: No
• INITIATION: Change From Baseline to Endpoint in 1,5 Anhydroglucitol (1,5 AG)
  • Time Frame: Baseline (Initiation), Endpoint (Week 24)
    Safety Issue?: No
• INITIATION: Incremental Change From Baseline in Body Weight
  • Time Frame: Baseline (Initiation), Weeks 6, 12, 18, 24, Endpoint (LOCF)
    Safety Issue?: Yes
• INITIATION: Body Weight
  • Time Frame: Baseline (Initiation), Weeks 6, 12, 18, 24, Endpoint (LOCF)
    Safety Issue?: Yes
• INITIATION: Percentage of Participants With Self-reported Hypoglycemic Episodes
  • Time Frame: Baseline (Initiation), Endpoint (Week 24), Overall (sum of frequencies of hypoglycemic episodes after baseline ([Week 0]).
    Safety Issue?: Yes
• INITIATION: Rate of Self-reported Hypoglycemic Episodes
  • Time Frame: Endpoint (Initiation: Week 24), Overall (incidence of hypoglycemic episodes after baseline [Week 0])
    Safety Issue?: Yes
• INITIATION: Insulin Dose
  • Time Frame: Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, Endpoint (LOCF)
    Safety Issue?: No
• INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Age
  • Time Frame: Endpoint (Initiation: Week 24)
    Safety Issue?: No
• INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Origin
  • Time Frame: Endpoint (Initiation: Week 24)
    Safety Issue?: No
• INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
  • Time Frame: Endpoint (Initiation: Week 24)
    Safety Issue?: No
• INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - HbA1c
  • Time Frame: Endpoint (Initiation: Week 24)
    Safety Issue?: No
• INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Baseline HbA1c Percentage Group
  • Time Frame: Endpoint (Initiation: Week 24)
    Safety Issue?: No
• INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - 1,5 AG
  • Time Frame: Endpoint (Initiation: Week 24)
    Safety Issue?: No
• INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Pre Meals Blood Glucose, Post Meals Blood Glucose, Average of All Blood Glucose, and Fasting Blood Glucose
  • Time Frame: Endpoint (Initiation: Week 24)
    Safety Issue?: No
• INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal - Oral Diabetes Medication at Baseline
  • Time Frame: Endpoint (Initiation: Week 24)
    Safety Issue?: No
• MAINTENANCE: HbA1c at Specified Visits and Endpoint
  • Time Frame: Baseline (Week 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: 7-point SMPG Profiles and Postprandial Excursions
  • Time Frame: Baseline (Maintenance: Week 24), Endpoint (LOCF) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Rate of Increase in HbA1c
  • Time Frame: Endpoint (LOCF) (Maintenance: up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Percentage of Participants With HbA1c < or = 7.0%, HbA1c <7.0, and HbA1c < or = 6.5%
  • Time Frame: Endpoint (LOCF) (Maintenance: up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Incremental Change From Baseline in Body Weight
  • Time Frame: Baseline (Week 0), Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: Yes
• MAINTENANCE: Body Weight
  • Time Frame: Baseline (Week 0), Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: Yes
• MAINTENANCE: Insulin Dose
  • Time Frame: Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Percentage of Participants With Self-reported Hypoglycemic Episodes
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years), Overall (incidence of hypoglycemic episodes after baseline (Week 0)
    Safety Issue?: Yes
• MAINTENANCE: Rate of Self-reported Hypoglycemic Episodes
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years), Overall (incidence of hypoglycemic episodes after baseline [Week 0])
    Safety Issue?: Yes
• MAINTENANCE: Change From Baseline in 1,5-Anhydroglucitol
  • Time Frame: Baseline (Maintenance: Week 24), Endpoint (LOCF) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Change From Baseline to Endpoint in HbA1c
  • Time Frame: Baseline (Week 0), Week 24, Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes Group
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes Group
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c Group
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c Group
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Oral Diabetes Medicine at Baseline
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Oral Diabetes Medicine at Baseline
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - 1,5 AG
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - 1,5 AG
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Mean of Post Meals Blood Glucose and Average of All Blood Glucose
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Mean of Post Meals Blood Glucose and Average of All Blood Glucose
  • Time Frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
    Safety Issue?: No
• ADDENDUM: Change in HbA1c From Point of Second Randomization (Addendum Baseline) to Endpoint
  • Time Frame: Baseline (Addendum: Week 24), Endpoint (24 weeks [Week 48])
    Safety Issue?: No
• ADDENDUM: Percentage of Participants With HbA1c < or = 7.0%, HbA1c < 7.0%, and < or = 6.5%
  • Time Frame: Endpoint (Addendum: 24 weeks [Week 48])
    Safety Issue?: No
• ADDENDUM: 7-point SMPG Profiles
  • Time Frame: Endpoint (Addendum: 24 weeks [Week 48])
    Safety Issue?: No
• ADDENDUM: Incremental Change From Baseline in Body Weight
  • Time Frame: Baseline (Addendum: Week 24), Weeks 6 (30 Weeks), 12 (36 Weeks), 24 (48 Weeks), Endpoint (LOCF)
    Safety Issue?: Yes
• ADDENDUM: Body Weight
  • Time Frame: Baseline (Addendum Week 24), Weeks 6 (30 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF)
    Safety Issue?: Yes
• ADDENDUM: Insulin Dose
  • Time Frame: Baseline (Addendum: Week 24), Weeks 1 (25 weeks), 2 (26 weeks), 3 (27 weeks), 4 (28 weeks), 5 (25 weeks), 6 (26 weeks), 8 (32 weeks), 10 (34 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF)
    Safety Issue?: No
• ADDENDUM: Percentage of Participants With Self-reported Hypoglycemic Episodes
  • Time Frame: Weeks 6 (Addendum: 30 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF)
    Safety Issue?: Yes
• ADDENDUM: Rate of Self-reported Hypoglycemic Episodes
  • Time Frame: Endpoint (Addendum 24 weeks), Overall (mean yearly rate of hypoglycemia during addendum phase
    Safety Issue?: Yes
• ADDENDUM: Change From Baseline in 1,5-Anhydroglucitol to Week 24
  • Time Frame: Baseline (addendum: 24 weeks), Endpoint (24 weeks: Week 48)
    Safety Issue?: No
• ADDENDUM: HbA1c at Specified Visits and Endpoint
  • Time Frame: Baseline (Addendum: 24 weeks), Weeks 12, 24, Endpoint (24 weeks: Week 48)
    Safety Issue?: No

Inclusion Criteria:

• Must have type 2 diabetes.
• Must be at least 30 and less than 80 years of age at the time of Visit 1.
• Must be on at least two oral antidiabetes medications for at least 90 days.
• Must have an HbA1c 1.2 to 2.0 times the upper limit of normal reference range at the local lab.

Exclusion Criteria:

• Must not have used insulin on a regular basis in the last 12 months.
• Must not have had more than one episode of severe hypoglycemia in the last 24 weeks.
• Must not have a body mass index (BMI) of greater than 45 (morbid obesity).
• Must not have clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal disease.
• Must not be pregnant or intend to get pregnant during course of the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: 79 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Eli Lilly and Company Industry

Overall Clinical Trial Officials and Contacts

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) Study Director Eli Lilly and Company  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00279201

Study ID Number: 10455

ClinicalTrials.gov Identifier: NCT00279201

Health Authority: United States: Food and Drug Administration

Lilly Clinical Trial Registry