The Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

The Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes. A 26 Week, Randomised, Open-label, Parallel-group, Multicentre, Multinational Trial With a 26 Week Extension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00856986
• Other study ID #: NN2211-1842
• Secondary ID: 2007-005317-19
• Status: Completed
• Phase: Phase 3
• First received: March 5, 2009
• Last updated: November 17, 2014
• Start date: March 2009
• Est. completion date: November 2010

Study information

• Verified date: November 2014
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHPCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthNetherlands: Medicines Evaluation Board, Dutch Health Care InspectorateSpain: Spanish Agency of MedicinesUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Europe and North America. The aim of this clinical trial is to assess and compare the effect of insulin detemir in combination with liraglutide and metformin versus liraglutide and metformin in subjects with type 2 diabetes. Subjects will continue their own pre-trial metformin treatment during the trial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 987
• Est. completion date: November 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subjects diagnosed with type 2 diabetes, insulin naïve and treated with metformin as monotherapy for at least 3 months prior to screening, at a stable dose of at least 1500 mg/day or metformin (at least 1500 mg/day) and a sulfonylurea (less than or equal to half of the maximum approved dose), both at a stable dose for at least 3 months prior to screening. Previous short-term insulin treatment in connection with intercurrent illness is allowed at the discretion of the Investigator

• HbA1c 7.0-10.0% (both inclusive) for subjects on metformin monotherapy

• HbA1c 7.0-8.5% (both inclusive) for subjects on metformin in combination with a sulphonylurea

Exclusion Criteria:

• Previous treatment with insulin (except for short-term treatment in connection with intercurrent illness at the discretion of the Investigator)

• Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria in a period of 3 months prior to screening

• Recurrent major hypoglycaemia or hypoglycaemic unawareness as judged by the Investigator

• Impaired kidney function

• Impaired liver function

• Uncontrolled treated/untreated hypertension

• Cancer or any clinically significant disease or disorder as judged by the Investigator

• Previous participation in the run-in phase of this trial. Re-screening is allowed once

• History of chronic pancreatitis or idiopathic pancreatitis

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• liraglutide
Liraglutide 1.8 mg/day for subcutaneous (under the skin) injection.
• insulin detemir
Insulin detemir subcutaneous (under the skin) injection once daily. Dose will be titrated (individually adjusted) based on fasting self-measured plasma glucose levels according to a pre-specified algorithm
• metformin
Metformin tablets, at least 1500 mg/day

Locations

Country	Name	City	State
Puerto Rico	Novo Nordisk Clinical Trial Call Center	Bayamon
Puerto Rico	Novo Nordisk Clinical Trial Call Center	Carolina
Puerto Rico	Novo Nordisk Clinical Trial Call Center	Trujillo Alto
United States	Novo Nordisk Clinical Trial Call Center	Atlanta	Georgia
United States	Novo Nordisk Clinical Trial Call Center	Baltimore	Maryland
United States	Novo Nordisk Clinical Trial Call Center	Bradenton	Florida
United States	Novo Nordisk Clinical Trial Call Center	Bronx	New York
United States	Novo Nordisk Clinical Trial Call Center	Charlotte	North Carolina
United States	Novo Nordisk Clinical Trial Call Center	Chattanooga	Tennessee
United States	Novo Nordisk Clinical Trial Call Center	Chicago	Illinois
United States	Novo Nordisk Clinical Trial Call Center	Chino	California
United States	Novo Nordisk Clinical Trial Call Center	Cincinnati	Ohio
United States	Novo Nordisk Clinical Trial Call Center	Cincinnati	Ohio
United States	Novo Nordisk Clinical Trial Call Center	Clearwater	Florida
United States	Novo Nordisk Clinical Trial Call Center	Corpus Christi	Texas
United States	Novo Nordisk Clinical Trial Call Center	Dallas	Texas
United States	Novo Nordisk Clinical Trial Call Center	Dallas	Texas
United States	Novo Nordisk Clinical Trial Call Center	Dallas	Texas
United States	Novo Nordisk Clinical Trial Call Center	Dallas	Texas
United States	Novo Nordisk Clinical Trial Call Center	Dallas	Texas
United States	Novo Nordisk Clinical Trial Call Center	Dayton	Ohio
United States	Novo Nordisk Clinical Trial Call Center	Decatur	Georgia
United States	Novo Nordisk Clinical Trial Call Center	Durham	North Carolina
United States	Novo Nordisk Clinical Trial Call Center	Fullerton	California
United States	Novo Nordisk Clinical Trial Call Center	Hyattsville	Maryland
United States	Novo Nordisk Clinical Trial Call Center	Inglewood	California
United States	Novo Nordisk Clinical Trial Call Center	La Jolla	California
United States	Novo Nordisk Clinical Trial Call Center	Los Gatos	California
United States	Novo Nordisk Clinical Trial Call Center	Louisville	Kentucky
United States	Novo Nordisk Clinical Trial Call Center	Madisonville	Kentucky
United States	Novo Nordisk Clinical Trial Call Center	Memphis	Tennessee
United States	Novo Nordisk Clinical Trial Call Center	Methuen	Massachusetts
United States	Novo Nordisk Clinical Trial Call Center	Miami	Florida
United States	Novo Nordisk Clinical Trial Call Center	Miami	Florida
United States	Novo Nordisk Clinical Trial Call Center	Miami	Florida
United States	Novo Nordisk Clinical Trial Call Center	Midland	Texas
United States	Novo Nordisk Clinical Trial Call Center	Milwaukee	Wisconsin
United States	Novo Nordisk Clinical Trial Call Center	New Hyde Park	New York
United States	Novo Nordisk Clinical Trial Call Center	Northport	New York
United States	Novo Nordisk Clinical Trial Call Center	Oklahoma City	Oklahoma
United States	Novo Nordisk Clinical Trial Call Center	Orem	Utah
United States	Novo Nordisk Clinical Trial Call Center	Philadelphia	Pennsylvania
United States	Novo Nordisk Clinical Trial Call Center	Plano	Texas
United States	Novo Nordisk Clinical Trial Call Center	Quincy	Illinois
United States	Novo Nordisk Clinical Trial Call Center	Richmond	Virginia
United States	Novo Nordisk Clinical Trial Call Center	Richmond	Virginia
United States	Novo Nordisk Clinical Trial Call Center	Rockville	Maryland
United States	Novo Nordisk Clinical Trial Call Center	Roswell	Georgia
United States	Novo Nordisk Clinical Trial Call Center	Savannah	Georgia
United States	Novo Nordisk Clinical Trial Call Center	Spring Valley	California
United States	Novo Nordisk Clinical Trial Call Center	St. Louis	Missouri
United States	Novo Nordisk Clinical Trial Call Center	State College	Pennsylvania
United States	Novo Nordisk Clinical Trial Call Center	Tustin	California
United States	Novo Nordisk Clinical Trial Call Center	Walnut Creek	California
United States	Novo Nordisk Clinical Trial Call Center	Waterbury	Connecticut
United States	Novo Nordisk Clinical Trial Call Center	Willkes Barre	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Puerto Rico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 26.		Week 0 (Randomisation), week 26	No
Secondary	Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (for Intensified Subjects in Original Treatment Group)		Week 0, Week 52	No
Secondary	Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (Values Before Intensification as LOCF)		Week 0, Week 52	No
Secondary	Mean Change From Randomisation in Fasting Plasma Glucose at Week 26		Week 0 (Randomisation), Week 26	No
Secondary	Mean Change From Randomisation in Fasting Plasma Glucose at Week 52		Week 0, Week 52	No
Secondary	Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 26	Calculated as an estimate of the change in mean prandial increment of plasma glucose after breakfast, lunch and dinner (from baseline/randomisation (week 0) to 26 weeks), respectively. Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after each of these three meals, respectively.	Week 0 (Randomisation), Week 26	No
Secondary	Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 52	Calculated as an estimate of the change in mean prandial increment of plasma glucose after breakfast, lunch and dinner (from baseline (week 0) to 52 weeks), respectively. Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after each of these three meals, respectively.	Week 0, Week 52	No
Secondary	Mean Change From Randomisation in Fasting Insulin at Week 26		Week 0 (Randomisation), Week 26	No
Secondary	Mean Change From Randomisation in Fasting Insulin at Week 52		Week 0 (Randomisation), Week 52	No
Secondary	Mean Change From Randomisation in Fasting Pro-insulin at Week 26.		Week 0 (Randomisation), Week 26	No
Secondary	Mean Change From Randomisation in Fasting Pro-insulin at Week 52		Week 0, Week 52	No
Secondary	Mean Change From Randomisation in Fasting C-peptide at Week 26.		Week 0 (Randomisation), Week 26	No
Secondary	Mean Change From Randomisation in Fasting C-peptide at Week 52.		Week 0, Week 52	No
Secondary	Mean Changes From Randomisation in Cholesterol Lipids at Week 26.	Cholesterol Lipids cover: Total Cholesterol, Low-density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), High Density Lipoprotein Cholesterol (HDL-C)	Week 0 (Randomisation), Week 26	No
Secondary	Mean Changes From Randomisation in Cholesterol Lipids at Week 52.	Cholesterol Lipids cover: Total Cholesterol, Low-density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), High Density Lipoprotein Cholesterol (HDL-C)	Week 0, Week 52	No
Secondary	Mean Change From Randomisation in Lipids: Triglycerides at Week 26		Week 0 (Randomisation), Week 26	No
Secondary	Mean Change From Randomisation in Lipids: Triglycerides at Week 52		Week 0, Week 52	No
Secondary	Mean Change From Randomisation in Lipids: Free Fatty Acids (FFA) at Week 26		Week 0 (Randomisation), Week 26	No
Secondary	Mean Change From Randomisation in Lipids: Free Fatty Acids (FFA) at Week 52		Week 0, Week 52	No
Secondary	Mean Change From Randomisation in Body Weight at Week 26		Week 0 (Randomisation), Week 26	No
Secondary	Mean Change From Randomisation in Body Weight at Week 52		Week 0, Week 52	No
Secondary	Mean Change From Randomisation in Waist Circumference at Week 26.		Week 0 (Randomisation), Week 26	No
Secondary	Mean Change From Randomisation in Waist Circumference at Week 52.		Week 0, Week 52	No
Secondary	Mean Change From Randomisation in Hip Circumference at Week 26		Week 0 (Randomisation), Week 26	No
Secondary	Mean Change From Randomisation in Hip Circumference at Week 52		Week 0, week 52	No
Secondary	Mean Change From Randomisation in Waist to Hip Ratio at Week 26	Waist to Hip Ratio is calculated by dividing Waist circumference with Hip circumference	Week 0 (Randomisation), Week 26	No
Secondary	Mean Change From Randomisation in Waist to Hip Ratio at Week 52	Waist to Hip Ratio is calculated by dividing Waist circumference with Hip circumference	Week 0, Week 52	No
Secondary	Mean Change From Randomisation in Blood Pressure (Systolic and Diastolic) at Week 26.		Week 0 (Randomisation), Week 26	No
Secondary	Mean Change From Randomisation in Blood Pressure (Systolic and Diastolic) at Week 52.		Week 0, Week 52	No
Secondary	Adverse Events From Run-in (Week -12) to Week 52		Run-in (week -12) to Week 52	No
Secondary	Hypoglycaemic Episodes (Excluding Outlier Subject), Weeks 0-26	Number of hypoglycaemic episodes from Week 0 to Week 26, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.	weeks 0-26	No
Secondary	Hypoglycaemic Episodes Weeks 0-52	Number of hypoglycaemic episodes from Week 0 to Week 52, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.	Week 0-52	No

External Links

•   Clinical Trials at Novo Nordisk