A Study Comparing Insulin Intensification Therapies in Patients With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01175811
First received: August 3, 2010
Last updated: October 29, 2013
Last verified: October 2013
  Purpose

The purpose of the study is to compare the effects on overall glycaemic control of two insulin intensification therapies.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Insulin Lispro Premix
Drug: Insulin Glargine
Drug: Insulin Lispro
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Comparison of Premixed and Basal-Bolus Insulin Intensification Therapies in Patients With Type 2 Diabetes Mellitus With Inadequate Glycaemic Control on Twice-daily Premixed Insulin

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change in Haemoglobin A1c (HbA1c) From Baseline to 24 Week Endpoint [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    Least Squares (LS) means are calculated using mixed model repeating measures (MMRM) with the change from baseline in HbA1c at all post baseline measurement as dependent variables, treatment, country, visit and treatment by visit interaction as fixed effects, baseline HbA1c value as a covariate and participant as a random effect.


Secondary Outcome Measures:
  • Change in HbA1c From Baseline to 12 Week Endpoint [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    Least Squares (LS) means are calculated using mixed model repeating measures (MMRM) with the change from baseline in HbA1c at all post baseline measurement as dependent variables, treatment, country, visit and treatment by visit interaction as fixed effects, baseline HbA1c value as a covariate and participant as a random effect.

  • The Percentage of Participants Who Achieved Haemoglobin A1c (HbA1c) Less Than or Equal to 6.5% and Less Than or Equal to 7% at 12 Weeks and 24 Weeks [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    The Percentage of participants achieving a haemoglobin A1c (HbA1c) less than or equal (<=) to 6.5% or 7% is defined as 100 multiplied by the number of participants with a HbA1c of the cut-off value (6% or 7%) divided by the number of participants exposed to study drug. Participants with missing HbA1c values at endpoint were treated as not achieving the HbA1c goal.

  • The 7-point Self-monitored Blood Glucose (SMBG) Profiles at Baseline, 12 Weeks and 24 Weeks. [ Time Frame: Baseline, 12 weeks, and 24 weeks ] [ Designated as safety issue: No ]
    7-point Self-monitored Blood Glucose (SMBG) Profiles are measures of blood glucose taken 7 times a day at the morning pre-meal, morning 2-hours post-meal, midday pre-meal, midday 2-hours post-meal, evening pre-meal, evening 2-hours post-meal, and 0300 hour [3 am]. Each participant took measures on 3 non-consecutive days and the average was calculated for each of the 7 time points. The mean of the 7-point averages was calculated for all the participants at baseline, Weeks 12 and 24.

  • Daily Dose of Insulin: Total, Basal, and Prandial [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in Body Mass Index (BMI) From Baseline to 12 and 24 Weeks [ Time Frame: Baseline, 12 weeks, and 24 weeks ] [ Designated as safety issue: No ]
    Body mass index is an estimate of body fat based on body weight divided by height squared. Least Squares (LS) means are calculated using mixed model repeating measures (MMRM) using change from baseline in BMI at all post baseline measurement as dependent variables, treatment, country, visit and treatment by visit interaction as fixed effects, baseline BMI value as a covariate and participants as a random effect.

  • Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With Hypoglycemic Episodes (Incidence) [ Time Frame: baseline through 24 weeks ] [ Designated as safety issue: Yes ]
    Incidence of hypoglycemic episodes is defined as 100 multiplied by the number of participants experiencing a hypoglycemic episode divided by the number of participants exposed to study drug. Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of <= 70 mg/dL (3.9 mmol/L).

  • The Rate of Hypoglycemic Episodes [ Time Frame: baseline through 24 weeks ] [ Designated as safety issue: Yes ]
    The rate of hypoglycemic episodes is defined as the mean number of hypoglycemic episodes per 30 days per participant. Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of <= 70 mg/dL (3.9 mmol/L).

  • Percentage of Participants Experiencing a Severe Hypoglycemic Episode [ Time Frame: baseline through 24 weeks ] [ Designated as safety issue: Yes ]
    Severe hypoglycemic episode is defined as any event requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. The percentage of participants experiencing a severe hypoglycemic episode is defined as the 100 multiplied by the number of participants experiencing a severe hypoglycemic episode divided by the number of participants exposed to study drug.


Enrollment: 402
Study Start Date: February 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Premixed Insulin
Twice daily (before breakfast and lunch) insulin lispro mix 50 (50% insulin lispro, 50% insulin lispro protamine suspension [LM50]) and once daily (before dinner) insulin lispro mix 25 (25% insulin lispro, 75% insulin lispro protamine suspension [LM25])
Drug: Insulin Lispro Premix
Participant dependent dose, administered subcutaneously for 24 weeks
Other Names:
  • Humalog Mix25
  • Humalog Mix50
  • LY275585
Active Comparator: Basal-Bolus
Once daily (bedtime) insulin glargine and three pre-meal insulin lispro
Drug: Insulin Glargine
Participant dependent dose, administered subcutaneously for 24 weeks
Drug: Insulin Lispro
Participant dependent dose, administered subcutaneously for 24 weeks
Other Names:
  • Humalog
  • LY275585

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Present with type 2 diabetes mellitus
  • Have been receiving twice-daily premixed insulin therapy with or without metformin and/or alpha-glucosidase inhibitors, for at least six months prior to study entry
  • Have Haemoglobin A1c (HbA1c) >7.0% and <12.0%

Exclusion Criteria:

  • Within the last 3 months prior to entry into the study, are taking any non-permitted glucose-lowering agents, or are taking any non-permitted oral antihyperglycaemic medications
  • 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.
  • Are women who are breastfeeding.
  • Have an irregular sleep/wake cycle (for example, participants who sleep during the day and work during the night).
  • Do not regularly consume three meals per day.
  • Have a body mass index >35 kilogram per square meter (kg/m^2).
  • Have had more than one episode of severe hypoglycaemia within 24 weeks prior to entry into the study.
  • Have cardiac disease with a functional status that is Class III or IV
  • Have a history of renal or liver disease
  • Have used less than or equal to 20 Units per day (U/day) of insulin during the past 90 days for more than 14 days (accumulated).
  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: NCT01175811

Locations
China
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.
Beijing, China, 100730
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.
Guang Zhou, China, 510515
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.
Kunming, China, 650032
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.
Nanjing, China, 210109
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.
Shanghai, China, 200080
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.
Xi'An, China, 710032
Korea, Republic of
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.
Daegu, Korea, Republic of, 705-718
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
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.
Seoul, Korea, Republic of, 130-702
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.
Yeongdeungpo-Gu, Korea, Republic of, 150-950
Taiwan
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.
Changhua, Taiwan, 500
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.
Kuei Shan Hsiang, Taiwan, 33305
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.
Sindian City, Taiwan, 23148
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.
Yong Kung City, Taiwan, 71004
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

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01175811     History of Changes
Other Study ID Numbers: 13492, F3Z-CR-IOQD
Study First Received: August 3, 2010
Results First Received: October 29, 2013
Last Updated: October 29, 2013
Health Authority: China: Food and Drug Administration
South Korea: Korea Food and Drug Administration (KFDA)
Taiwan : Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Metabolic Diseases
Diabetes Mellitus, Type 2
Glargine
Diabetes Mellitus
Insulin LISPRO
Insulin

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

ClinicalTrials.gov processed this record on July 26, 2014