The Efficacy of Insulin Degludec/Liraglutide as add-on Therapy in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on Sulphonylurea With or Without Metformin Therapy

Diabetes Mellitus, Type 2 Clinical Trial

— DUAL™IV  

Official title:

The Efficacy of Insulin Degludec/Liraglutide as add-on Therapy in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on Sulphonylurea With or Without Metformin Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01618162
• Other study ID #: NN9068-3951
• Secondary ID: 2012-000140-97U1
• Status: Completed
• Phase: Phase 3
• First received: June 11, 2012
• Last updated: September 26, 2017
• Start date: August 29, 2012
• Est. completion date: October 23, 2013

Study information

• Verified date: September 2017
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Asia, Europe and the United States of America (USA). The aim of this trial is to investigate the efficacy and safety of insulin degludec/liraglutide in insulin naïve subjects inadequately controlled with SU (sulphonylurea) alone or in combination with metformin. All subjects will continue their pre-trial SU treatment with or without metformin treatment without changing the frequency or dose throughout the trial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 435
• Est. completion date: October 23, 2013
• Est. primary completion date: October 23, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects with type 2 diabetes mellitus

• HbA1c 7.0-9.0% (53-75 mmol/mol) (both inclusive)

• Subjects on stable daily dose of sulphonylurea (above or equal to half of the max approved dose according to local label) with or without metformin (above or equal to 1500 mg or max tolerated dose) for at least 90 days prior to screening visit (Visit 1)

• Body Mass Index (BMI) below or equal to 40 kg/m^2

Exclusion Criteria:

• Any use of oral anti-diabetic drugs (OADs) (other than SU in monotherapy or in combinationwith metformin) below or equal to 90 days prior to screening visit (Visit 1)

• Use of any drug (other than SU in monotherapy or in combination with metformin), which in the Investigators opinion could interfere with the blood glucose level (e.g. systemic corticosteroids)

• Previous treatment with glucagon-like peptide-1 (GLP-1) receptor agonist (e.g. exenatide, liraglutide)

• Treatment with any insulin regimen (short term treatment due to intercurrent illness including gestational diabetes is allowed at the discretion of the Investigator)

• Screening calcitonin above or equal to 50 ng/l

• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2)

• Cardiovascular disorders defined as: congestive heart failure (New York Heart Association (NYHA) class III-IV), diagnosis of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the past 52 weeks prior to screening visit (Visit 1) and/or planned coronary,carotid or peripheral artery revascularisation procedures

• Proliferative retinopathy requiring acute treatment or maculopathy (macular oedema) according to the Investigator's opinion

• Subjects with a clinical significant, active (during the past 12 months) disease of the gastrointestinal, pulmonary, endocrinological (except for the Type 2 Diabetes Mellitus),neurological, genitourinary or haematological system that in the opinion of the Investigator,may confound the results of the trial or pose additional risk in administering trial product

• History of chronic pancreatitis or idiopathic acute pancreatitis

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• insulin degludec/liraglutide
Injected subcutaneously (under the skin) once daily. Dose individually adjusted.
• placebo
Injected subcutaneously (under the skin) once daily.

Locations

Country	Name	City	State
Bulgaria	Novo Nordisk Investigational Site	Lukovit
Bulgaria	Novo Nordisk Investigational Site	Ruse
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Sofia
Canada	Novo Nordisk Investigational Site	Burnaby	British Columbia
Canada	Novo Nordisk Investigational Site	Cambridge	Ontario
Canada	Novo Nordisk Investigational Site	London	Ontario
Canada	Novo Nordisk Investigational Site	Mirabel	Quebec
Canada	Novo Nordisk Investigational Site	Pointe Claire	Quebec
Canada	Novo Nordisk Investigational Site	Quebec
Canada	Novo Nordisk Investigational Site	Sherbrooke	Quebec
Canada	Novo Nordisk Investigational Site	Surrey	British Columbia
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Canada	Novo Nordisk Investigational Site	Victoria	British Columbia
Germany	Novo Nordisk Investigational Site	Esslingen
Germany	Novo Nordisk Investigational Site	Hamburg
Germany	Novo Nordisk Investigational Site	Hohenmölsen
Germany	Novo Nordisk Investigational Site	Münster
Germany	Novo Nordisk Investigational Site	Pohlheim
Germany	Novo Nordisk Investigational Site	Rehlingen-Siersburg
Germany	Novo Nordisk Investigational Site	Sulzbach-Rosenberg
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Belgaum	Karnataka
India	Novo Nordisk Investigational Site	Delhi	New Delhi
India	Novo Nordisk Investigational Site	Guwahati	Assam
India	Novo Nordisk Investigational Site	Guwahati	Assam
India	Novo Nordisk Investigational Site	Hyderabad
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	Pune	Maharashtra
Israel	Novo Nordisk Investigational Site	Haifa
Israel	Novo Nordisk Investigational Site	Holon
Israel	Novo Nordisk Investigational Site	Jerusalem
Israel	Novo Nordisk Investigational Site	Kfar Saba
Israel	Novo Nordisk Investigational Site	Petah-Tikva
Israel	Novo Nordisk Investigational Site	Tel Hashomer
Israel	Novo Nordisk Investigational Site	Tel-Aviv
Puerto Rico	Novo Nordisk Investigational Site	Manati
Turkey	Novo Nordisk Investigational Site	Ankara
Turkey	Novo Nordisk Investigational Site	Antalya
Turkey	Novo Nordisk Investigational Site	Gaziantep
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Izmir
United States	Novo Nordisk Investigational Site	Anaheim	California
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Beaver	Pennsylvania
United States	Novo Nordisk Investigational Site	Chattanooga	Tennessee
United States	Novo Nordisk Investigational Site	Chesterfield	Missouri
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Crestview Hills	Kentucky
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Franklin	Ohio
United States	Novo Nordisk Investigational Site	Garden Grove	California
United States	Novo Nordisk Investigational Site	Greer	South Carolina
United States	Novo Nordisk Investigational Site	Gurnee	Illinois
United States	Novo Nordisk Investigational Site	Hurst	Texas
United States	Novo Nordisk Investigational Site	Kingsport	Tennessee
United States	Novo Nordisk Investigational Site	Kissimmee	Florida
United States	Novo Nordisk Investigational Site	La Jolla	California
United States	Novo Nordisk Investigational Site	Lodi	New Jersey
United States	Novo Nordisk Investigational Site	Long Beach	California
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Mason	Ohio
United States	Novo Nordisk Investigational Site	Melbourne	Florida
United States	Novo Nordisk Investigational Site	Meridian	Idaho
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Nashua	New Hampshire
United States	Novo Nordisk Investigational Site	Nashville	Tennessee
United States	Novo Nordisk Investigational Site	Newport News	Virginia
United States	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma
United States	Novo Nordisk Investigational Site	Pelzer	South Carolina
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Richmond	Virginia
United States	Novo Nordisk Investigational Site	Rockville	Maryland
United States	Novo Nordisk Investigational Site	Roswell	Georgia
United States	Novo Nordisk Investigational Site	Saint Charles	Missouri
United States	Novo Nordisk Investigational Site	Salt Lake City	Utah
United States	Novo Nordisk Investigational Site	San Mateo	California
United States	Novo Nordisk Investigational Site	Simpsonville	South Carolina
United States	Novo Nordisk Investigational Site	Spartanburg	South Carolina
United States	Novo Nordisk Investigational Site	Sugar Land	Texas
United States	Novo Nordisk Investigational Site	Tabor City	North Carolina
United States	Novo Nordisk Investigational Site	Troy	Michigan
United States	Novo Nordisk Investigational Site	Walnut Creek	California
United States	Novo Nordisk Investigational Site	West Seneca	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Germany,  India,  Israel,  Puerto Rico,  Turkey, 

References & Publications (2)

Khunti K, Mohan V, Jain SM, Boesgaard TW, Begtrup K, Sethi B. Efficacy and Safety of IDegLira in Participants with Type 2 Diabetes in India Uncontrolled on Oral Antidiabetic Drugs and Basal Insulin: Data from the DUAL Clinical Trial Program. Diabetes Ther. 2017 Jun;8(3):673-682. doi: 10.1007/s13300-017-0252-9. Epub 2017 Mar 22. — View Citation

Rodbard HW, Bode BW, Harris SB, Rose L, Lehmann L, Jarlov H, Thurman J; Dual Action of Liraglutide and insulin degludec (DUAL) IV trial investigators. Safety and efficacy of insulin degludec/liraglutide (IDegLira) added to sulphonylurea alone or to sulpho — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycosylated Haemoglobin (HbA1c)	Change in HbA1c from baseline to 26 weeks.	Week 0, Week 26
Secondary	Responders Achieving Pre-defined Target: HbA1c Below 7.0% (53 mmol/Mol)	Percentage of subjects having HbA1c below 7% at week 26.	Week 26
Secondary	Responders Achieving Pre-defined Target: HbA1c Below or Equal to 6.5% (48 mmol/Mol)	Percentage of subjects having HbA1c below 6.5% at week 26	Week 26
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG)	Change from baseline in FPG at week 26.	Week 0, week 26
Secondary	Change From Baseline in Body Weight	Change from baseline in body weight at week 26.	Week 0, week 26
Secondary	Number of Treatment Emergent (Confirmed) Hypoglycaemic Episodes	An event was treatment emergent if the onset of the episode occurs after the first administration of trial product and no later than 7 days after last trial product administration.; Confirmed hypoglycaemic episodes were defined as hypoglycaemic episodes that were either severe or minor.; Minor hypoglycaemic episodes were defined as: An episode with symptoms consistent with hypoglycaemia and confirmed by blood glucose value <2.8 mmol/L (50 mg/dL) or plasma glucose <3.1 mmol/L (56 mg/dL) and which was handled by the subject himself/herself.; Any asymptomatic PG value <3.1 mmol/L (56 mg/dL) or blood glucose value <2.8 mmol/L (50 mg/dL).; Severe hypoglycemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.; Reported values are hypoglycemia event rate per 100 patient-years of exposure (PYE).	After 26 weeks of treatment
Secondary	Number of Adverse Events (AEs)	An AE was any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. Reported values are hypoglycemia event rate per 100 PYE.	After 26 weeks of treatment

External Links

•   Clinical Trials at Novo Nordisk