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Comparison of Two Basal Insulins for Patients With Type 2 Diabetes (IOOY)

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00494013
Collaborator
(none)
442
Enrollment
56
Locations
2
Arms
13
Duration (Months)
7.9
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the effectiveness and safety of insulin lispro protamine suspension (ILPS) as compared to insulin detemir as basal insulin therapy in adults with type 2 diabetes. A gatekeeper strategy will be employed for sequentially testing the secondary objectives.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
442 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Treat-to-Target Comparison of Two Basal Insulin Analogs (Insulin Lispro Protamine Suspension and Comparator) in Basal Therapy for Patients With Type 2 Diabetes Mellitus
Study Start Date :
Aug 1, 2007
Actual Primary Completion Date :
Sep 1, 2008
Actual Study Completion Date :
Sep 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: Insulin Lispro Protamine Suspension

Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks.

Drug: Insulin Lispro Protamine Suspension
Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks.
Other Names:
  • Neutral Protamine Lispro (NPL)
  • Humalog
  • ILPS

    		•
    Active Comparator: Detemir

    Detemir: Patient specific dose administered subcutaneously once or twice daily x 24 weeks.

    Drug: Detemir
    Patient specific dose administered subcutaneously once or twice daily x 24 weeks.

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c) [Baseline, 24 Weeks]

    Secondary Outcome Measures

    1. Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks [Baseline, 12 Weeks, 24 Weeks]

    2. Percentage of Patients With HbA1c <7.0% and HbA1c < or = 6.5% at Endpoint [24 Weeks]

      Percentage of patients achieving Hemaglobin A1c (HbA1c) targets of less than 7.0% and less than or equal to 6.5% at endpoint.

    3. Glycemic Variability [24 Weeks]

      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-monitoring blood glucose [SMBG] profiles at endpoint) for the actual morning pre-meal blood glucose value.

    4. 7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint [24 Weeks]

      Actual daily mean blood glucose levels at endpoint.

    5. Number of Participants With Self-reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall for All Study Periods [Baseline to 24 Weeks]

      Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. Results are for the combined titration and maintenance periods.

    6. 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall [Baseline to 24 Weeks]

      Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. 1-year adjusted rate=(total number of episodes between 2 time intervals/number of days between intervals) X 365.25 days.

    7. 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall [Baseline to 24 Weeks]

      Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. 30-day adjusted rate=(total number of episodes between 2 time intervals/number of days between intervals) X 30 days.

    8. Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint [Baseline, 24 Weeks]

    9. Total Daily Insulin Dose (Units) at Endpoint [24 Weeks]

      Insulin dose at endpoint was analyzed by 24-hour total daily insulin (units).

    10. Total Daily Insulin Dose Per Body Weight (Units/Kilograms) at Endpoint [24 Weeks]

      Insulin dose at endpoint was analyzed by 24-hour total daily insulin per body weight (Units/kilograms).

    11. Number of Injections of Basal Insulin Analog at Endpoint [24 Weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Have type 2 diabetes mellitus for at least 1 year.

    2. Are at least 18 years old.

    3. Have been receiving oral antihyperglycemic medications (OAMs), without insulin, for at least 3 months immediately prior to the study and have been on stable doses of at least 2 of the following OAMs for the 6 weeks prior to Visit 1, at or above the doses defined in the following: Metformin--1500 milligrams per day (mg/day); Sulfonylureas--1/2 the maximum daily dose, according to the local package insert; Dipeptidyl peptidase-intravenous (DPP-IV) inhibitors-- 1/2 the maximum daily dose, according to the local package insert; Thiazolidinediones (TZDs)--30 mg/day pioglitazone or 4 mg/day rosiglitazone.

    4. Have a hemoglobin A1c (HbA1c) greater than or equal to 7.5% and less than or equal to 10.0%, as measured by a central laboratory before Visit 2.

    5. Body mass index (BMI) greater than or equal to 25 and less than or equal to 45 kilograms per square meter (kg/m2).

    Exclusion Criteria

    1. Have used insulin therapy (outside of pregnancy) any time in the past 2 years, except for short-term treatment of acute conditions, and up to a maximum of 4 weeks.

    2. Have taken any glucose-lowering medications not included in Inclusion Criterion [3] (for example, acarbose, miglitol, pramlintide, exenatide, repaglinide, or nateglinide) in the past 3 months before Visit 1.

    3. Have had more than 1 episode of severe hypoglycemia, within 6 months prior to entry into the study, or is currently diagnosed as having hypoglycemia unawareness.

    4. Have a history of renal transplantation or are currently receiving renal dialysis or creatinine greater than or equal to 2.0 milligrams per deciliter (mg/dL) (177 micromoles per liter [micromol/L]).

    5. Have obvious clinical signs or symptoms, or laboratory evidence, of liver disease (alanine transaminase [ALT], or aspartate transaminase [AST] greater than 2 times the upper limit of the reference range, as defined by the local laboratory) or have albumin value above or below the normal reference range, as defined by the local laboratory.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    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. Hueytown Alabama United States 35023
    2 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. Litchfield Park Arizona United States 85340
    3 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. Phoenix Arizona United States 85016
    4 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. Buena Park California United States 90620
    5 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. Fountain Valley California United States 92708
    6 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. Los Angeles California United States 90057
    7 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. Jacksonville Florida United States 32257
    8 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. Atlanta Georgia United States 30312
    9 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. Chicago Illinois United States 60612
    10 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. Evansville Indiana United States 47714
    11 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. Indianapolis Indiana United States 46202
    12 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. Newburgh Indiana United States 47630
    13 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. Lexington Kentucky United States 40503
    14 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. Slidell Louisiana United States 70458
    15 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. Prince Frederick Maryland United States 20678
    16 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. Novi Michigan United States 48374
    17 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. Las Vegas Nevada United States 89101
    18 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. Syracuse New York United States 13210
    19 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. Goldsboro North Carolina United States 27530
    20 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. Cincinnati Ohio United States 45236
    21 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. London Ohio United States 43140
    22 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. Bend Oregon United States 97701
    23 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. Lansdale Pennsylvania United States 19446
    24 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. Taylors South Carolina United States 29687
    25 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. Johnson City Tennessee United States 37604
    26 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. Grand Prairie Texas United States 75052
    27 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. Menomonee Falls Wisconsin United States 53051
    28 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. Buenos Aires Argentina C1188AAF
    29 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. Ramos Mejia Argentina B1704ETD
    30 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. Budapest Hungary H-1139
    31 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. Eger Hungary 3300
    32 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. Mako Hungary 6900
    33 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. Szekesfehervar Hungary 8000
    34 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. Szekszard Hungary 7100
    35 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. Veszprem Hungary 8200
    36 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. Bangalore India 560052
    37 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. Chennai India 600086
    38 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. Cochin India 682026
    39 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. Mumbai India 400 067
    40 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. Pune India 411011
    41 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. Goyang-Si Korea, Republic of 410-719
    42 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. Sungnam-Si Korea, Republic of 463-712
    43 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. Chihuahua Mexico 31238
    44 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. Guadalajara Mexico 44340
    45 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. Krakow Poland 30-349
    46 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. Poznan Poland 61-495
    47 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. Rzeszow Poland 35-068
    48 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. Lugo Spain 27004
    49 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. Palma de Mallorca Spain 07014
    50 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. Santa Cruz de Tenerife Spain 38320
    51 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. Valencia Spain 46015
    52 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. Chiayi City Taiwan 600
    53 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. Neihu Taipei Taiwan 114
    54 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. Tainan Taiwan 704
    55 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. Taipei Taiwan 100
    56 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. Yung-Kang, Tainan Taiwan 710

    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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00494013
    Other Study ID Numbers:
    • 10935
    • F3Z-MC-IOOY
    First Posted:
    Jun 29, 2007
    Last Update Posted:
    Nov 11, 2009
    Last Verified:
    Nov 1, 2009
    Keywords provided by , ,
    diabetes
    type 2
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Insulin Lispro
    Protamines

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 789 patients were screened; 347 patients failed screening or discontinued before randomization. Demographics and outcomes are reported on the "Full Analysis Set": all randomized patients who received at least one dose of study drug and had at least one post-baseline measurement for the dependent variable, according to Intent to Treat principles.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Period Title: Overall Study
    STARTED 223 219
    Full Analysis Set (Intent to Treat) 219 210
    COMPLETED 193 183
    NOT COMPLETED 30 36

    Baseline Characteristics

    Arm/Group Title Insulin Lispro Protamine Suspension Detemir Total
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks. Total of all reporting groups
    Overall Participants 219 210 429
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    56.32
    (9.91)
    55.73
    (10.20)
    56.03
    (10.04)
    Sex: Female, Male (Count of Participants)
    Female
    108
    49.3%
    97
    46.2%
    205
    47.8%
    Male
    111
    50.7%
    113
    53.8%
    224
    52.2%
    Region of Enrollment (participants) [Number]
    Argentina
    10
    4.6%
    11
    5.2%
    21
    4.9%
    Hungary
    36
    16.4%
    34
    16.2%
    70
    16.3%
    India
    42
    19.2%
    39
    18.6%
    81
    18.9%
    Korea, Republic of
    10
    4.6%
    11
    5.2%
    21
    4.9%
    Mexico
    28
    12.8%
    27
    12.9%
    55
    12.8%
    Spain
    13
    5.9%
    13
    6.2%
    26
    6.1%
    Taiwan
    20
    9.1%
    19
    9%
    39
    9.1%
    United States
    60
    27.4%
    56
    26.7%
    116
    27%
    Race/Ethnicity (participants) [Number]
    African
    8
    3.7%
    8
    3.8%
    16
    3.7%
    Caucasian
    88
    40.2%
    82
    39%
    170
    39.6%
    East Asian
    35
    16%
    33
    15.7%
    68
    15.9%
    Hispanic
    45
    20.5%
    47
    22.4%
    92
    21.4%
    West Asian
    43
    19.6%
    40
    19%
    83
    19.3%
    Sulfonylurea Group (participants) [Number]
    Yes
    170
    77.6%
    158
    75.2%
    328
    76.5%
    No
    49
    22.4%
    51
    24.3%
    100
    23.3%
    Unavailable
    0
    0%
    1
    0.5%
    1
    0.2%
    Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]
    30.03
    (5.01)
    30.10
    (5.12)
    30.06
    (5.06)
    Body Weight (kilograms (kg)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms (kg)]
    81.10
    (17.46)
    82.72
    (19.32)
    81.89
    (18.39)
    Duration of Diabetes (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    9.48
    (6.09)
    8.94
    (5.59)
    9.22
    (5.85)
    Height (centimeters (cm)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [centimeters (cm)]
    163.94
    (10.19)
    165.14
    (10.94)
    164.53
    (10.57)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c)
    Description
    Time Frame Baseline, 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement. Last observation carried forward.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Measure Participants 219 210
    Baseline (n=209, n=202)
    8.79
    (0.06)
    8.77
    (0.06)
    Change from Baseline (n=209, n=202)
    -1.52
    (0.08)
    -1.31
    (0.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments Hypothesis: Basal analog insulin lispro protamine suspension, injected once or twice daily is noninferior to basal analog insulin determir, injected once or twice daily, with regard to glycemic control as measured by change in HbA1c from baseline to endpoint (last observation carried forward).
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The noninferiority margin was 0.4%.
    Statistical Test of Hypothesis p-Value 0.026
    Comments
    Method ANCOVA
    Comments ANCOVA Model: Variable=Treatment + Baseline + Country + Baseline Sulfonylurea Group.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.21
    Confidence Interval () 95%
    -0.39 to -0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments The two-sided 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Determir).
    2. Secondary Outcome
    Title Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks
    Description
    Time Frame Baseline, 12 Weeks, 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Measure Participants 219 210
    Baseline
    8.79
    (0.06)
    8.77
    (0.06)
    Week 12 HbA1c
    7.44
    (0.08)
    7.55
    (0.07)
    Week 12 Change from Baseline
    -1.33
    (0.08)
    -1.22
    (0.07)
    Week 24 HbA1c
    7.14
    (0.09)
    7.34
    (0.08)
    Week 24 Change from Baseline
    -1.63
    (0.09)
    -1.43
    (0.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.213
    Comments P-value for 12 Week Change from Baseline.
    Method ANCOVA
    Comments ANCOVA Model: Variable = Treatment + Baseline + Country + Baseline Sulfonylurea Group.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.11
    Confidence Interval () 95%
    -0.28 to 0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments The two-sides 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Detemir).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.213
    Comments P-value for 12 Week HbA1c.
    Method ANCOVA
    Comments ANCOVA Model: Variable = Treatment + Baseline + Country + Baseline Sulfonylurea Group.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.11
    Confidence Interval () 95%
    -0.28 to 0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments The two-sided 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Detemir).
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.038
    Comments P-value for 24 Week Change from Baseline.
    Method ANCOVA
    Comments ANCOVA Model: Variable = Treatment + Baseline + Country + Baseline Sulfonylurea Group.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.20
    Confidence Interval () 95%
    -0.38 to -0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments The two-sides 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Detemir).
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.038
    Comments P-value for Week 24 HbA1c.
    Method ANCOVA
    Comments ANCOVA Model: Variable = Treatment + Baseline + Country + Baseline Sulfonylurea Group.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.20
    Confidence Interval () 95%
    -0.38 to -0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments The two-sided 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Detemir).
    3. Secondary Outcome
    Title Percentage of Patients With HbA1c <7.0% and HbA1c < or = 6.5% at Endpoint
    Description Percentage of patients achieving Hemaglobin A1c (HbA1c) targets of less than 7.0% and less than or equal to 6.5% at endpoint.
    Time Frame 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement. Last observation carried forward.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Measure Participants 219 210
    HbA1c <7.0%
    34.9
    15.9%
    31.2
    14.9%
    HbA1c ≤6.5%
    22.5
    10.3%
    16.3
    7.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.463
    Comments P-value for HbA1c <7.0%.
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.135
    Comments P-value for HbA1c ≤6.5%.
    Method Fisher Exact
    Comments
    4. Secondary Outcome
    Title Glycemic Variability
    Description 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-monitoring blood glucose [SMBG] profiles at endpoint) for the actual morning pre-meal blood glucose value.
    Time Frame 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement. Last observation carried forward.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Measure Participants 218 208
    Mean (Standard Deviation) [millimoles per Liter (mmol/L)]
    1.14
    (0.64)
    1.04
    (0.69)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments The first gatekeeping hypothesis was that Insulin Lispro Protamine Suspension was noninferior to determir.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority margin of 0.8 millimoles per Liter (mmol/L).
    Statistical Test of Hypothesis p-Value 0.107
    Comments
    Method ANOVA
    Comments ANOVA model: Variable=Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.10
    Confidence Interval () 95%
    -0.02 to 0.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments The two-sided 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Determir).
    5. Secondary Outcome
    Title 7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint
    Description Actual daily mean blood glucose levels at endpoint.
    Time Frame 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement. Last observation carried forward.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Measure Participants 219 210
    Average 7-Point SMBG
    8.25
    (1.58)
    8.26
    (1.73)
    Average Pre-Meal
    7.48
    (1.69)
    7.43
    (1.69)
    Average Post-Meal
    9.37
    (1.91)
    9.42
    (2.21)
    Average Morning+Evening Pre-Meal
    7.49
    (1.68)
    7.40
    (1.86)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.952
    Comments P-value for Average 7-Point SMBG.
    Method ANOVA
    Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.856
    Comments P-value for Average Pre-Meal.
    Method ANOVA
    Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.790
    Comments P-value for Average Post-Meal.
    Method ANOVA
    Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.632
    Comments P-value for Average Morning+Evening Pre-Meal.
    Method ANOVA
    Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
    6. Secondary Outcome
    Title Number of Participants With Self-reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall for All Study Periods
    Description Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. Results are for the combined titration and maintenance periods.
    Time Frame Baseline to 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Measure Participants 219 210
    All Hypoglycemic Episodes
    151
    68.9%
    137
    65.2%
    Nocturnal Hypoglycemic Episodes
    99
    45.2%
    68
    32.4%
    Severe Hypoglycemic Episodes (N=214, N=207)
    5
    2.3%
    2
    1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.472
    Comments P-value for All Hypoglycemic Events.
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments P-value for Nocturnal Hypoglycemic Events.
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.450
    Comments P-value for Severe Hypoglycemic Events.
    Method Fisher Exact
    Comments
    7. Secondary Outcome
    Title 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall
    Description Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. 1-year adjusted rate=(total number of episodes between 2 time intervals/number of days between intervals) X 365.25 days.
    Time Frame Baseline to 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Measure Participants 219 210
    Hypoglycemic Rate
    24.23
    (32.99)
    16.23
    (26.05)
    Nocturnal Hypoglycemic Rate
    6.32
    (12.11)
    3.75
    (13.18)
    Severe Hypoglycemic Rate
    0.05
    (0.45)
    0.01
    (0.15)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments P-value for Hypoglycemic Rate.
    Method ANOVA
    Comments Nonparametric ANOVA Model: Rank of Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments P-value for Nocturnal Hypoglycemic Rate.
    Method ANOVA
    Comments Nonparametric ANOVA Model: Rank of Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.226
    Comments P-value for Severe Hypoglycemic Rate.
    Method ANOVA
    Comments Nonparametric ANOVA Model: Rank of Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
    8. Secondary Outcome
    Title 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall
    Description Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. 30-day adjusted rate=(total number of episodes between 2 time intervals/number of days between intervals) X 30 days.
    Time Frame Baseline to 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Measure Participants 219 210
    Hypoglycemic Rate
    1.99
    (2.71)
    1.33
    (2.14)
    Nocturnal Hypoglycemic Rate
    0.52
    (0.99)
    0.31
    (1.08)
    Severe Hypoglycemic Rate
    0.00
    (0.04)
    0.00
    (0.01)
    9. Secondary Outcome
    Title Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint
    Description
    Time Frame Baseline, 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement. Last observation carried forward.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Measure Participants 219 209
    Baseline
    81.10
    (17.46)
    82.56
    (19.22)
    Change from Baseline
    1.88
    (3.16)
    0.36
    (2.85)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments The second gatekeeping hypothesis was that Insulin Lispro Protamine Suspension was noninferior to detemir with regard to change in absolute body weight from baseline to endpoint (last observation carried forward).
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority margin of 1.5 kilograms (kg).
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value for Change from Baseline.
    Method ANCOVA
    Comments ANCOVA Model: Variable=Treatment + Baseline + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 1.50
    Confidence Interval () 95%
    0.93 to 2.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments The two-sided 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Determir).
    10. Secondary Outcome
    Title Total Daily Insulin Dose (Units) at Endpoint
    Description Insulin dose at endpoint was analyzed by 24-hour total daily insulin (units).
    Time Frame 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement. Last observation carried forward.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Measure Participants 219 210
    Mean (Standard Deviation) [Units of insulin]
    31.78
    (19.14)
    37.30
    (29.45)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.074
    Comments
    Method ANCOVA
    Comments ANCOVA Model: Variable=Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group + Change in HbA1c from Baseline.
    11. Secondary Outcome
    Title Total Daily Insulin Dose Per Body Weight (Units/Kilograms) at Endpoint
    Description Insulin dose at endpoint was analyzed by 24-hour total daily insulin per body weight (Units/kilograms).
    Time Frame 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement. Last observation carried forward.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Measure Participants 219 210
    Mean (Standard Deviation) [Units of Insulin/kilograms (U/kg)]
    0.39
    (0.23)
    0.46
    (0.36)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.039
    Comments
    Method ANCOVA
    Comments ANCOVA Model: Variable=Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group + Change in HbA1c from Baseline.
    12. Secondary Outcome
    Title Number of Injections of Basal Insulin Analog at Endpoint
    Description
    Time Frame 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement. Last observation carried forward.
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    Measure Participants 219 210
    Patients with 1 Injection
    89
    40.6%
    108
    51.4%
    Patients with 2 Injections
    130
    59.4%
    102
    48.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Protamine Suspension, Detemir
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.026
    Comments
    Method Fisher Exact
    Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Insulin Lispro Protamine Suspension Detemir
    Arm/Group Description Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks.
    All Cause Mortality
    Insulin Lispro Protamine Suspension Detemir
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Insulin Lispro Protamine Suspension Detemir
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/219 (3.2%) 1/210 (0.5%)
    Infections and infestations
    Bronchitis 1/219 (0.5%) 1 0/210 (0%) 0
    Cellulitis 0/219 (0%) 0 1/210 (0.5%) 1
    Injury, poisoning and procedural complications
    Fall 1/219 (0.5%) 1 0/210 (0%) 0
    Operative haemorrhage 1/219 (0.5%) 1 0/210 (0%) 0
    Rib fracture 1/219 (0.5%) 1 0/210 (0%) 0
    Metabolism and nutrition disorders
    Hypoglycaemia 2/219 (0.9%) 4 0/210 (0%) 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain 1/219 (0.5%) 1 0/210 (0%) 0
    Tenosynovitis 1/219 (0.5%) 1 0/210 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung neoplasm malignant 1/219 (0.5%) 1 0/210 (0%) 0
    Other (Not Including Serious) Adverse Events
    Insulin Lispro Protamine Suspension Detemir
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 78/219 (35.6%) 70/210 (33.3%)
    Eye disorders
    Diabetic retinopathy 4/219 (1.8%) 4 2/210 (1%) 2
    Gastrointestinal disorders
    Diarrhoea 6/219 (2.7%) 8 7/210 (3.3%) 7
    Gastritis 5/219 (2.3%) 5 2/210 (1%) 2
    Nausea 2/219 (0.9%) 4 4/210 (1.9%) 5
    Vomiting 4/219 (1.8%) 4 2/210 (1%) 2
    General disorders
    Chest pain 1/219 (0.5%) 1 3/210 (1.4%) 3
    Oedema peripheral 3/219 (1.4%) 3 1/210 (0.5%) 2
    Pain 0/219 (0%) 0 3/210 (1.4%) 3
    Pyrexia 5/219 (2.3%) 5 1/210 (0.5%) 1
    Infections and infestations
    Bronchitis 2/219 (0.9%) 3 3/210 (1.4%) 3
    Gastroenteritis 4/219 (1.8%) 4 1/210 (0.5%) 1
    Influenza 4/219 (1.8%) 4 3/210 (1.4%) 5
    Nasopharyngitis 12/219 (5.5%) 14 10/210 (4.8%) 10
    Sinusitis 3/219 (1.4%) 3 0/210 (0%) 0
    Upper respiratory tract infection 6/219 (2.7%) 7 7/210 (3.3%) 8
    Investigations
    Weight increased 5/219 (2.3%) 5 0/210 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/219 (0.5%) 1 3/210 (1.4%) 3
    Back pain 3/219 (1.4%) 3 3/210 (1.4%) 3
    Muscle spasms 3/219 (1.4%) 3 3/210 (1.4%) 3
    Nervous system disorders
    Dizziness 2/219 (0.9%) 2 4/210 (1.9%) 7
    Headache 5/219 (2.3%) 6 8/210 (3.8%) 8
    Respiratory, thoracic and mediastinal disorders
    Cough 3/219 (1.4%) 3 3/210 (1.4%) 3
    Skin and subcutaneous tissue disorders
    Pruritus 1/219 (0.5%) 1 4/210 (1.9%) 4
    Vascular disorders
    Hypertension 4/219 (1.8%) 4 3/210 (1.4%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00494013
    Other Study ID Numbers:
    • 10935
    • F3Z-MC-IOOY
    First Posted:
    Jun 29, 2007
    Last Update Posted:
    Nov 11, 2009
    Last Verified:
    Nov 1, 2009