A Comparison Study of Basal Bolus Therapies Together With Lispro Insulin in Type 2 Diabetes Patients

A Prospective Randomized Trial to Compare Basal Bolus Therapies That Use Either Insulin Lispro Protamine Suspension or Insulin Glargine Together With Lispro Insulin in Patients With Type 2 Diabetes

This study is designed to look at if a basal bolus regimen of insulin lispro protamine suspension (ILPS) provides the same glycemic control as a basal bolus regimen of insulin glargine (when one basal bolus regimen is injected once daily together with insulin lispro injected 2-3 times daily).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Insulin Glargine; Drug: Insulin Lispro; Drug: Insulin Lispro Protamine Suspension (ILPS)

• Study Type: Interventional
• Enrollment (Actual): 374
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Genk, Belgium, 3600
    • 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.
  • Leuven, Belgium, 3000
    • 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.
  • Willebroek, Belgium, 2830
    • 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.
• Czech Republic
  • Holesov, Czech Republic, 769 01
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  • Hranice I-Mesto, Czech Republic, 753 01
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  • Olomouc, Czech Republic, 77200
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  • Ostrava, Czech Republic, 709 00
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  • Plzen, Czech Republic, 301 66
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  • Prague, Czech Republic, 149 00
    • 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.
• Germany
  • Bad Mergentheim, Germany, D-97980
    • 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.
  • Berlin, Germany, D-12351
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  • Damme, Germany, D-49401
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  • Dresden, Germany, D-01219
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  • Hamburg, Germany, D-22177
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  • Hannover, Germany, 30519
    • 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.
  • Pirna, Germany, 01796
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  • Rotenburg-Fulda, Germany, D-36199
    • 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.
• Greece
  • Athens, Greece, 11526
    • 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.
  • Larissa, Greece, 41221
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  • Thessaloniki, Greece, 56429
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• Italy
  • Ancona, Italy, 60131
    • 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.
  • Bari, Italy, 70124
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  • Milano, Italy, 20162
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  • Padova, Italy, 35143
    • 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.
  • Pistoia, Italy, 51100
    • 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.
  • Ravenna, Italy, 48100
    • 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.
  • Rome, Italy, 00189
    • 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.
• Poland
  • Gorzow Wielkopolski, Poland, 66-400
    • 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, 31-159
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  • Lodz, Poland, 93-338
    • 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.
  • Lubin, Poland, 59-301
    • 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.
  • Mielec, Poland, 39-300
    • 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, 61-696
    • 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.
  • Warsaw, Poland, 02-577
    • 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.
  • Wroclaw, Poland, 503-349
    • 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.
• Romania
  • Baia Mare, Romania, 430071
    • 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.
  • Bucharest, Romania, 020475
    • 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.
  • Cluj-Napoca, Romania, 400006
    • 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.
  • Sf Gheorghe, Romania
    • 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.
• Slovakia
  • Banska Bystrica, Slovakia, 97405
    • 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.
  • Bratislava, Slovakia, 821 06
    • 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.
  • Modra, Slovakia, 900 01
    • 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.
  • Nitra, Slovakia, 94901
    • 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.
• Turkey
  • Bornova, Turkey, 35100
    • 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.
  • Istanbul, Turkey, 34662
    • 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.
  • Izmir, Turkey, 35360
    • 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.
• United Kingdom
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH3 9YW
      • 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.
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S5 7AU
      • 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.
  • Warwickshire
    • Rugby, Warwickshire, United Kingdom, CV22 5PX
      • 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.
  • West Midlands
    • West Bromwich, West Midlands, United Kingdom, B71 4HJ
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diabetes Mellitus, Type 2
• Have been receiving metformin and at least one other oral antihyperglycemic medication (sulfonylurea or thiazolidinedione) with insulin for at least 3 months prior to Visit 1 (Screening)
• Hemoglobin A1C (HbA1c) greater than or equal to 7.5% and less than or equal to 11.0%
• Body Mass Index (BMI) greater than or equal to 25 and less than or equal to 45 kg/m^2
• Capable and willing to follow the protocol
• Give written consent

Exclusion Criteria:

• Are taking any glucose-lowering agents (other than those listed in the inclusion criteria above)
• Have a history of severe hypoglycemia in the past 6 months
• Are pregnant or may become pregnant
• Women who are breastfeeding
• Have significant cardiac disease
• Have significant renal or liver disease
• Undergoing therapy for a malignancy
• Contraindications to the study medications
• Have an irregular sleep/wake cycle
• Have a serious disease or any condition considered by the investigator to be exclusionary

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Glargine; Glargine plus Insulin Lispro (2-3 injections)	Drug: Insulin Glargine; patient glucose-level dependent, injection, once daily in the evening, 24 weeks; Drug: Insulin Lispro; subcutaneous injections prior to meals, 24 weeks
Experimental: ILPS; Insulin Lispro Protamine Suspension (ILPS) plus Insulin Lispro (2-3 injections)	Drug: Insulin Lispro; subcutaneous injections prior to meals, 24 weeks; Drug: Insulin Lispro Protamine Suspension (ILPS); patient glucose-level dependent, injection, once daily in the evening, 24 weeks; Other Names: LY275585

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c) to Week 24	Least Squares Mean (LSMean) values reported in the table were controlled for treatment, country, and baseline HbA1c value.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c at Week 12 and Week 24	LSMean values presented were controlled for treatment, country, baseline HbA1C value and week.	Baseline, Week 12, Week 24
Percentage of Participants With HbA1c Less Than 7.0% and Less Than or Equal to 6.5% at Endpoint		Week 24
7-point Self-monitored Blood Glucose Profiles (SMBG) at Endpoint	LSMean values presented were controlled for treatment, country, and baseline HbA1C value. SMBG at morning pre-meal, morning postprandial, midday pre-meal, midday postprandial, evening pre-meal, evening postprandial, 0300 hours. Postprandial glucose is measured 2 hours after the start of the meal.	24 weeks
Glycemic Variability at Endpoint	LSMeans were controlled for treatment and country grouping (Mediterranean, rest of Europe). Glycemic variability was assessed as the standard deviations of 4 fasting SMBG samples, 4 post-breakfast measurements, 4 post-lunch measurements, 4 post-evening meal measurements.	Week 24
Rate Of All Self-reported Hypoglycemic Episodes	Rate of self-reported hypoglycemic episodes, all, non-nocturnal,and nocturnal, severe, documented ≤3.9 mmol/L and ≤3.0 mmol/L. Rate=episodes/30 days/patient/. Episode=any time a patient has a symptom associated with hypoglycemia or blood glucose level of ≤70 mg/dL,even if not associated with symptoms.Overall=any time post-randomization in the study period. Nocturnal=Episode between bedtime and waking. Non-Nocturnal=Episode between waking and bedtime.Severe:episode in which patient requires assistance,and has glucose <50 mg/dL or prompt recovery after oral carbohydrate, glucagon, or IV glucose.	Baseline through Week 24
Percentage of Participants With Self-Reported Hypoglycemic Episodes	Episode=any time a patient feels that he/she is experiencing a sign or symptom associated with hypoglycemia or has a blood glucose level of ≤70 mg/dL, even if not associated with signs,symptoms, or treatment. Overall=any time post-randomization visits in the study period. Nocturnal=Episode that occurs between bedtime and waking. Non-Nocturnal=Episode occurring between waking and bedtime. Severe=episode with symptoms of neuroglycopenia in which patient requires assistance,and has blood glucose value <50 mg/dL or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose.	Baseline through Week 24
Number of Participants With Adverse Events (AE)	A listing of adverse events is located in the Reported Adverse Event module.	Baseline through Week 24
Change in Body Weight From Baseline to Week 24	LSMean values presented were controlled for treatment, country, and baseline HbA1C value.	Baseline, Week 24
Total Daily Insulin Dose at Endpoint	LSMean values presented were controlled for treatment, country, and baseline HbA1C value.	Week 24
Number of Injections of Insulin at Week 24		Week 24

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: April 23, 2008
• First Submitted That Met QC Criteria: April 23, 2008
• First Posted (Estimate): April 25, 2008

Study Record Updates

• Last Update Posted (Estimate): May 13, 2011
• Last Update Submitted That Met QC Criteria: May 11, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Coagulants; Heparin Antagonists; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Lispro; Protamines
• Other Study ID Numbers: 12047 (DAIDS-ES Registry Number); F3Z-EW-IOPJ (Other Identifier: Eli Lilly and Company)