To Evaluate the Effect of Liraglutide Versus Glimepiride (Amaryl®) on Haemoglobin A1c - Full Text View

Sponsor:	Novo Nordisk
Information provided by (Responsible Party):	Novo Nordisk
ClinicalTrials.gov Identifier:	NCT00294723

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 Mellitus, Type 2	Drug: liraglutide Drug: glimepiride Drug: placebo	Phase III

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:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Glimepiride Liraglutide

U.S. FDA Resources

Further study details as provided by Novo Nordisk:

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00294723

Show 108 Study Locations

Sponsors and Collaborators

Novo Nordisk

Investigators

Study Director:

Paula Hale, MD

Novo Nordisk

More Information

Additional Information:

Clinical Trials at Novo Nordisk This link exits the ClinicalTrials.gov site

No publications provided by Novo Nordisk

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Buse JB, Garber A, Rosenstock J, Schmidt WE, Brett JH, Videbæk N, Holst J, Nauck M. Liraglutide treatment is associated with a low frequency and magnitude of antibody formation with no apparent impact on glycemic response or increased frequency of adverse events: results from the Liraglutide Effect and Action in Diabetes (LEAD) trials. J Clin Endocrinol Metab. 2011 Jun;96(6):1695-702. Epub 2011 Mar 30.

Hegedüs L, Moses AC, Zdravkovic M, Le Thi T, Daniels GH. GLP-1 and calcitonin concentration in humans: lack of evidence of calcitonin release from sequential screening in over 5000 subjects with type 2 diabetes or nondiabetic obese subjects treated with the human GLP-1 analog, liraglutide. J Clin Endocrinol Metab. 2011 Mar;96(3):853-60. Epub 2011 Jan 5.

Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B; LEAD-3 (Mono) Study Group. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009 Feb 7;373(9662):473-81. Epub 2008 Sep 24.

Responsible Party:	Novo Nordisk
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:	September 22, 2011
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
Glimepiride
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs

Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on February 09, 2012