Comparison of Two Basal Insulin Therapies for Patients With Type 1 Diabetes (IOOZ)

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00487240
First received: June 14, 2007
Last updated: October 20, 2010
Last verified: October 2010
  Purpose

The purpose of this study is to examine the efficacy and safety of insulin lispro protamine suspension (ILPS) as compared to insulin detemir as basal insulin combined with mealtime insulin therapy in patients with type 1 diabetes. A gatekeeper strategy will be employed for sequentially testing the secondary objectives.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Drug: Insulin Lispro Protamine Suspension
Drug: Insulin Levemir
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: Comparison of Two Basal Insulin Analogs (Insulin Lispro Protamine Suspension and Insulin Detemir) in Basal-Bolus Therapy for Patients With Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint [ Time Frame: baseline and 32 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Actual and Change From Baseline Hemoglobin A1c (HbA1c) Values [ Time Frame: Baseline, 8,16, 24, 32 Weeks ] [ Designated as safety issue: No ]
    The summary statistics represents the mean of all subjects. Change from baseline is calculated for each individual subject for the specific visit and then the "mean change from baseline" is calculated by averaging out for all subjects. [Sum over all (i) {A1c at Week 8 for Subject(i) minus A1c Baseline for Subject (i)}/Total Subjects]. Therefore, for example, the Change from Baseline is not equal to the difference of Mean A1c for Week 8 minus Mean A1c for baseline.

  • Percentage of Patients With Hemoglobin A1c (HbA1c) Less Than or Equal to 7.0% and HbA1c Less Than or Equal to 6.5% [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
  • 7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    Actual daily mean blood glucose levels at endpoint. The SMBG excursion is the difference between the postprandial and preprandial blood glucose concentration taken at the morning, midday and evening meals.

  • Glycemic Variability at Endpoint [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    Glycemic variability was measured by standard deviation (SD) value of fasting blood glucose as measured by intra-patient glycemic variability (determined by the 7-point self-monitored blood glucose [SMBG] profiles at endpoint); mean value (M-value), which was the mean of the intra-days self-monitored blood glucose values, and by the mean of daily difference (MODD), which was the mean of the between-days self-monitored blood glucose values.

  • Number of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe Hypoglycemia) Overall and at Endpoint [ Time Frame: Baseline to 32 Weeks ] [ Designated as safety issue: Yes ]
    Nocturnal: Defined as any hypoglycemic event that occurs between bedtime and waking. Non-Nocturnal: Defined as any hypoglycemic event that occurs between waking and bedtime. Severe: An episode with symptoms consistent with neuroglycopenia in which the patient requires the assistance of another person; associated with either a blood glucose level of <2.8 mmol/L (<50 mg/dL) or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose.

  • 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint [ Time Frame: baseline to 32 weeks ] [ Designated as safety issue: Yes ]
    Nocturnal: Defined as any hypoglycemic event that occurs between bedtime and waking. Non-Nocturnal: Defined as any hypoglycemic event that occurs between waking and bedtime. Severe: An episode with symptoms consistent with neuroglycopenia in which the patient requires the assistance of another person; associated with either a blood glucose level of <2.8 mmol/L (<50 mg/dL) or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose.

  • 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint [ Time Frame: baseline to 32 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline in Absolute Body Weight at 32 Week Endpoint [ Time Frame: Baseline, 32 Weeks ] [ Designated as safety issue: No ]
  • Insulin Dose Per Body Weight (Total and By Component [Basal and Bolus]) [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    Total daily insulin dose adjusted for body weight (U/kg/day) was assessed.

  • Insulin Dose (Total and By Component [Basal and Bolus]) [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
    Total daily insulin dose (U/day) was assessed.


Enrollment: 387
Study Start Date: June 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Insulin Lispro Protamine Suspension
Insulin Lispro Protamine Suspension twice daily
Drug: Insulin Lispro Protamine Suspension
Patient specific dose, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks.
Other Names:
  • ILPS
  • NPL
  • Humalog
  • LY275585
Active Comparator: Detemir
Insulin Levemir (detemir) subcutaneous (SC) twice daily.
Drug: Insulin Levemir
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks

Detailed Description:

Phase 3b, randomized, multicenter, multinational, open-label, two-arm, active control, parallel study to determine safety, efficacy, and noninferiority of basal analog insulin lispro protamine suspension (ILPS, also referred to as NPL [neutral protamine Hagedorn]), injected two times a day, compared with basal analog insulin detemir, injected two times a day, as measured by change in hemoglobin A1c (HbA1c) from baseline (Visit 2) to 32 weeks in adult patients with type 1 diabetes when used in combination with bolus insulin lispro, injected three times a day.

  Eligibility

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

Inclusion Criteria:

  • Clinical diagnosis of type 1 diabetes for one year or more
  • Age 18 years or older
  • Body mass index (BMI) less than or equal to 35 kilograms per square meter (kg/m2)
  • Have a hemoglobin A1c (HbA1c) 1.2 to 2.0 times the upper limit of the normal (ULN) reference range within 30 days prior to Visit 1 or collected and analyzed at a local laboratory at Visit 1
  • As determined by the investigator, are capable and willing to do the following:

    • perform self monitoring of blood glucose (SMBG),
    • complete patient diaries as required for this protocol,
    • use the insulin injection device(s) according to the instructions provided,
    • are receptive to diabetes education,
    • comply with the required study visits.

Exclusion Criteria:

  • Have taken any oral antihyperglycemic medications (OAMs) within 3 months prior to Visit 1.
  • Have had more than one episode of severe hypoglycemia, as defined in the Abbreviations and Definitions section of the protocol, within 6 months prior to entry into the study
  • Are pregnant or intend to become pregnant during the course of the study or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable or women who are breastfeeding
  • Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intra-articular, intraocular, and inhaled preparations) or have received such therapy within the 4 weeks immediately preceding Visit 1.
  • Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
  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: NCT00487240

  Show 28 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
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

Additional Information:
Publications:
Responsible Party: Chief Medical Office, Eli Lilly
ClinicalTrials.gov Identifier: NCT00487240     History of Changes
Other Study ID Numbers: 10937, F3Z-MC-IOOZ
Study First Received: June 14, 2007
Results First Received: August 17, 2009
Last Updated: October 20, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
diabetes
type 1

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
Protamines
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Heparin Antagonists
Molecular Mechanisms of Pharmacological Action
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2014