To Evaluate the Effect of Liraglutide Versus Glimepiride (Amaryl®) on Haemoglobin A1c (LEAD-3)

This study has been terminated.
(The trial was terminated at week 195 due to an insufficient number of subjects remaining to obtain reasonable statistical power)
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00294723
First received: February 20, 2006
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

This trial is conducted in North America (the United States of America (USA) and Mexico).

The trial is designed to evaluate the effects of treatment with liraglutide versus glimepiride in subjects with type 2 diabetes. The trial is a 52-week randomised, double-blind trial period plus a 52-week open-label extension (week 104) followed by an additional 156-week continued open-label extension. The total duration of the treatment period is planned to be 260 weeks (5 years).


Condition Intervention Phase
Diabetes
Diabetes Mellitus, Type 2
Drug: liraglutide
Drug: glimepiride
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Liraglutide Effect and Action in Diabetes (LEAD-3): Effect on Glycemic Control of Liraglutide Versus Glimepiride in Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:
  • Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 [ Time Frame: week 0, week 52 ] [ Designated as safety issue: No ]
    Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 52 weeks (end of double-blind period)

  • Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104 [ Time Frame: week 0, week 104 ] [ Designated as safety issue: No ]
    Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 104 weeks (end of 52-week extension)

  • Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156 [ Time Frame: week 0, week 156 ] [ Designated as safety issue: No ]
    Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 156 weeks


Secondary Outcome Measures:
  • Change in Body Weight at Week 52 [ Time Frame: week 0, week 52 ] [ Designated as safety issue: No ]
    Change in body weight from baseline (week 0) to 52 weeks (end of double-blind period)

  • Change in Body Weight at Week 104 [ Time Frame: week 0, week 104 ] [ Designated as safety issue: No ]
    Change in body weight from baseline (week 0) to 104 weeks (end of 52-week extension)

  • Change in Body Weight at Week 156 [ Time Frame: week 0, week 156 ] [ Designated as safety issue: No ]
    Change in body weight from baseline (week 0) to 156 weeks

  • Change in Fasting Plasma Glucose at Week 52 [ Time Frame: week 0, week 52 ] [ Designated as safety issue: No ]
    Change in fasting plasma glucose (FPG) from baseline (week 0) to 52 weeks (end of double-blind period)

  • Change in Fasting Plasma Glucose at Week 104 [ Time Frame: week 0, week 104 ] [ Designated as safety issue: No ]
    Change in fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of 52-week extension)

  • Change in Fasting Plasma Glucose at Week 156 [ Time Frame: week 0, week 156 ] [ Designated as safety issue: No ]
    Change in fasting plasma glucose (FPG) from baseline (week 0) to 156 weeks

  • Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52 [ Time Frame: week 0, week 52 ] [ Designated as safety issue: No ]
    Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 52 weeks (end of double-blind period). The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.

  • Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104 [ Time Frame: week 0, week 104 ] [ Designated as safety issue: No ]
    Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 104 weeks (end of 52-week extension). The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.

  • Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156 [ Time Frame: week 0, week 156 ] [ Designated as safety issue: No ]
    Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 156 weeks. The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.

  • Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52 [ Time Frame: week 0, week 52 ] [ Designated as safety issue: No ]
    Change in mean prandial increments of plasma glucose from baseline (week 0) to 52 weeks (end of double-blind period). The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.

  • Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104 [ Time Frame: week 0, week 104 ] [ Designated as safety issue: No ]
    Change in mean prandial increments of plasma glucose from baseline (week 0) to 104 weeks (end of 52-week extension). The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.

  • Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156 [ Time Frame: week 0, week 156 ] [ Designated as safety issue: No ]
    Change in mean prandial increments (incr.) of plasma glucose from baseline (week 0) to 156 weeks. The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.

  • Hypoglycaemic Episodes [ Time Frame: weeks 0-104 ] [ Designated as safety issue: Yes ]
    Total number of hypoglycaemic episodes occuring from baseline (week 0) to 104 weeks (end of the 52-week extension). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 56 mg/dL. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 56 mg/dL.

  • Hypoglycaemic Episodes [ Time Frame: weeks 104-195 ] [ Designated as safety issue: Yes ]
    Total number of hypoglycaemic episodes occuring from week 104 to end of trial (week 195). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 56 mg/dL. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 56 mg/dL.


Enrollment: 746
Study Start Date: February 2006
Study Completion Date: March 2010
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lira 1.8
Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195).
Drug: liraglutide
1.8 mg for s.c. (under the skin) injection
Drug: placebo
Glimepiride placebo, 8mg capsule
Experimental: Lira 1.2
Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195).
Drug: liraglutide
1.2 mg for s.c. (under the skin) injection
Drug: placebo
Glimepiride placebo, 8mg capsule
Active Comparator: Glimepiride - 1
Glimepiride 8 mg once daily + liraglutide placebo 200 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195).
Drug: glimepiride
8 mg capsule
Drug: placebo
Liraglutide placebo, 200 mcl
Active Comparator: Glimepiride - 2
Glimepiride 8 mg once daily + liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195).
Drug: glimepiride
8 mg capsule
Drug: placebo
Liraglutide placebo, 300 mcl

  Eligibility

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

Inclusion Criteria:

  • Type 2 diabetes
  • TTreatment with diet/exercise or with not more than half maximal dose of oral anti-diabetic drugs alone for at least 2 months
  • Diet/exercise treated subjects with HbA1c between 7.0% and 11%, inclusive
  • OAD (oral anti-diabetic drug) treated subjects with HbA1c between 7.0% and 10%, inclusive
  • Body Mass Index (BMI) less than or equal to 45 kg/m^2

Exclusion Criteria:

  • Treatment with insulin for the last 3 months, except short-term treatment for intercurrent illness
  • Treatment with any drug that could interfere with the glucose level (besides use of a single anti-diabetic compound)
  • Any serious medical condition
  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: NCT00294723

  Show 113 Study Locations
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
  More Information

Additional Information:
No publications provided by Novo Nordisk A/S

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00294723     History of Changes
Obsolete Identifiers: NCT00853359
Other Study ID Numbers: NN2211-1573
Study First Received: February 20, 2006
Results First Received: February 23, 2010
Last Updated: June 25, 2014
Health Authority: Mexico: Federal Commission for Protection Against Health Risks
United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Liraglutide
Glimepiride
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 22, 2014