Pre-Mix Insulin Lispro Treatment for Type 2 Diabetes Patients Who Consume a Light Breakfast

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00664534
First received: April 21, 2008
Last updated: November 9, 2011
Last verified: November 2011
  Purpose

This study is designed to look at how best to start and then gradually intensify (as needed) the insulin lispro premix regimen in type 2 diabetes patients who consume a light breakfast.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Insulin Glargine
Drug: Insulin Lispro Premix (mid-mixture and low-mixture)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison of Premixed Insulin Lispro Low-Mixture and Mid-Mixture Regimens With Separate Basal and Bolus Insulin Injections in Patients With Type 2 Diabetes With Inadequate Glycemic Control on Oral Therapy Who Consume Light Breakfast

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Baseline Adjusted Glycosylated Hemoglobin (HbA1c) at Endpoint [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Least Squares Mean (LSMean) values were adjusted based on a fixed effect linear regression model: HbA1c = Treatment + Country + HbA1c baseline value + Ramadan holiday between Visit 10 (Week 36) and Visit 12 (Week 48) (yes/no) in per-protocol (PP) population.


Secondary Outcome Measures:
  • Percentage of Participants Using Each Possible Final Insulin Regimen [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

    Insulin Regimens:

    Lispro: Mid-Mix (MM) before noon; Low-Mix (LM) before evening (PM); MM before noon+LM before PM; LM before morning (AM)+MM before noon + LM before PM; MM before AM +MM before noon+LM before PM Glargine: Glargine once a day (QD); Glargine QD + 1 Lispro (noon or PM); Glargine QD + 2 Lispro (noon and PM); Glargine QD + 3 Lispro.


  • HbA1c Over Time [ Time Frame: 16 weeks, 32 weeks, and 48 weeks ] [ Designated as safety issue: No ]
    Least Squares Mean (LSMean) values were adjusted based on a mixed effect linear regression model with a participant specific random effect: HbA1c = Treatment + Country + HbA1c baseline value + Ramadan holiday between Visit 10 (Week 36) and Visit 12 (Week 48) (yes/no) + visit + visit*treatment in Full Analysis Set (FAS) Population.

  • Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time [ Time Frame: 16 weeks, 32 weeks and 48 weeks ] [ Designated as safety issue: No ]
  • 7-point Self-monitored Blood Glucose Profiles [ Time Frame: 16 weeks, 32 weeks and 48 weeks ] [ Designated as safety issue: No ]
  • Mean Postprandial Blood Glucose Values [ Time Frame: Baseline, 16 weeks, 32 weeks and 48 weeks ] [ Designated as safety issue: No ]
    Mean postprandial blood glucose values were assessed using GlycoMark, which is an FDA-approved blood test measuring levels of 1,5 anhydroglucitol (1,5 AG) in serum or plasma. When 1,5 AG values decrease, serum glucose levels increase.

  • Mean Daily Total, Basal and Prandial Insulin Dose [ Time Frame: 16 weeks, 32 weeks and 48 weeks ] [ Designated as safety issue: No ]
  • Body Weight Change From Baseline to Endpoint [ Time Frame: baseline, 48 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of All Self-reported Hypoglycemic Episodes [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: Yes ]
    Percentage of participants with self-reported hypoglycemic episodes at any time during the study. A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has a blood glucose level of ≤70 mg/dL (3.9 mmol/L) (Roche plasma glucose) or ≤75 mg/dL (4.2 mmol/L) (IFCC Plasma Values), even if it was not associated with signs, symptoms, or treatment consistent with current guidelines (ADA 2005).

  • Rate Per 30 Days of All Self-reported Hypoglycemic Episodes [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: Yes ]
    The hypoglycemia rate between two visits will be calculated as the total number of episodes between the two visits divided by the number of days between the visits, and then multiplied by 30 days (rate per patient per 30 days).

  • Number of Participants With Adverse Events [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: Yes ]

    A summary of serious adverse events (SAEs) and all other non-serious treatment-emergent adverse events (TEAE) is located in the Reported Adverse Event Module.

    TEAEs are defined as events that are newly reported after randomization or reported to worsen in severity from baseline.



Enrollment: 344
Study Start Date: April 2008
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Glargine
Glargine +/- 1,2 or 3 injections of insulin lispro plus oral antihyperglycemic medications (OAMs)
Drug: Insulin Glargine
patient glucose-level dependent, injection, as needed per patient glucose level, 48 weeks
Experimental: Premixed Insulin Lispro
Premixed Insulin Lispro (mid-mixture or low-mixture) 1,2 or 3 injections plus OAMs
Drug: Insulin Lispro Premix (mid-mixture and low-mixture)
patient glucose level dependent, injection, as needed per patient glucose level, 48 weeks
Other Name: LY275585

  Eligibility

Ages Eligible for Study:   30 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diabetes Mellitus, Type 2
  • have been receiving metformin plus at least one other oral antihyperglycemic medication (OAM) (sulfonylurea or Thiazolidinedione [TZD]) without insulin, for at least 90 days prior to Visit 1
  • glycosylated hemoglobin (HbA1c) greater than or equal to 7.0% and less than 11.0%
  • regularly consume a light breakfast (less than 15% of total daily calorie intake)
  • capable and willing to follow the protocol
  • give written consent

Exclusion Criteria:

  • are taking a TZD whose country label does not allow in combination with insulin
  • are taking any glucose-lowering agents (other than specified in the inclusion criteria above)
  • have a body mass index greater than 40 kg/m^2
  • have a history of severe hypoglycemia in past 24 weeks
  • 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 study medications
  • have an irregular sleep/wake cycle
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00664534

Locations
Canada, Ontario
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.
Smiths Falls, Ontario, Canada, K7A 4W8
Egypt
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Alexandria, Egypt
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Bab El Louk, Egypt
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Cairo, Egypt, 11562
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Heliopolis, Egypt
India
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Ahmedabad, India, 380006
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Hyderabaad, India, 500033
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Indore, India, 452001
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Mumbai, India, 400053
Mexico
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Coatzacoalcos, Mexico, 96400
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Mexico City, Mexico, 06700
Portugal
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Aveiro, Portugal, 3814-501
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Barreiro, Portugal, 2830
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Lisbon, Portugal, 1250-203
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Porto, Portugal, 4099-001
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.
Bucharest, Romania, 020359
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Craiova, Romania, 200000
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Galati, Romania, 6200
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Iasi, Romania, 70057
Spain
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Alicante, Spain, 03114
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Badalona, Spain, 08915
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Madrid, Spain, 28040
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Palma De Mallorca, Spain, 07198
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Santa Cruz De Tenerife, Spain, 38320
Turkey
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Ankara, Turkey, 06510
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Antalya, Turkey, 07070
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Konya, Turkey, 42075
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:
No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00664534     History of Changes
Other Study ID Numbers: 11806, F3Z-EW-S020, CTRI/2009/091/000609
Study First Received: April 21, 2008
Results First Received: November 9, 2011
Last Updated: November 9, 2011
Health Authority: Romania: National Medicines Agency
Spain: Ethics Committee
Spain: Spanish Agency of Medicines
Canada: Health Canada
Mexico: Ministry of Health
Mexico: Ethics Committee
Brazil: National Committee of Ethics in Research
Egypt: Ministry of Health and Population
Saudi Arabia: Research Advisory Council
Portugal: Ethics Committee for Clinical Research
Portugal: National Pharmacy and Medicines Institute
Turkey: Ministry of Health

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin LISPRO
Glargine
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014