The Efficacy of Insulin Degludec/Liraglutide in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on GLP-1 Receptor Agonist and OAD Therapy

Diabetes Mellitus, Type 2 Clinical Trial

— DUAL™ III  

Official title:

The Efficacy of Insulin Degludec/Liraglutide in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on GLP-1 Receptor Agonist and OAD Therapy (DUAL™ III -GLP-1 Switch)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01676116
• Other study ID #: NN9068-3851
• Secondary ID: 2012-000209-63U1
• Status: Completed
• Phase: Phase 3
• Start date: August 29, 2012
• Est. completion date: March 11, 2014

Study information

• Verified date: December 2018
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Europe, Oceania and the United States of America (USA).

The aim of the trial is to investigate the efficacy of insulin degludec/liraglutide in controlling glycaemia in adults with type 2 diabetes inadequately controlled on glucagon-like peptide-1 (GLP-1) receptor agonist and OAD therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 438
• Est. completion date: March 11, 2014
• Est. primary completion date: March 11, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects with type 2 diabetes mellitus

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

• Treatment with daily GLP-1 receptor agonist at maximum dose according to local label (i.e. 1.8 mg once daily (OD) Victoza® (liraglutide) or 10 microgram twice daily (BID) Byetta® (exenatide)) or documented maximum tolerated dose (i.e. 1.2 mg OD Victoza® (liraglutide) or 5 microgram BID Byetta® (exenatide)) in combination with a stable daily dose of metformin (equal to or above 1500 mg or documented maximum tolerated dose) for 90 days or more prior to screening visit (Visit 1)

• BMI (body mass index) equal to or below 40 kg/m^2

Exclusion Criteria:

• Any use of oral anti-diabetic drugs (OADs) (except for metformin, pioglitazone and sulphonylurea) for 90 days or less prior to screening visit (Visit 1)

• Use of any drug (except metformin,pioglitazone, sulphonylurea and GLP-1 receptor agonist) which in the Investigator's opinion could interfere with the blood glucose level (e.g. systemic corticosteroids)

• 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 equal to or above 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 clinically 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 products

• 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. Subjects will continue their pre-trial OAD treatment without changing the frequency or dose throughout the trial.
• liraglutide
Subjects will continue on their pre-trial treatment of liraglutide (Victoza®) (GLP-1 receptor agonist) + OAD without changing the frequency or dose throughout the trial.
• exenatide
Subjects will continue on their pre-trial treatment of exenatide (Byetta®) (GLP-1 receptor agonist) + OAD without changing the frequency or dose throughout the trial.

Locations

Country	Name	City	State
Australia	Novo Nordisk Investigational Site	Box Hill	Victoria
Australia	Novo Nordisk Investigational Site	Coffs Harbour	New South Wales
Australia	Novo Nordisk Investigational Site	Keswick	South Australia
Australia	Novo Nordisk Investigational Site	Melbourne	Victoria
Australia	Novo Nordisk Investigational Site	Merewether	New South Wales
France	Novo Nordisk Investigational Site	Antibes
France	Novo Nordisk Investigational Site	Boulogne Billancourt
France	Novo Nordisk Investigational Site	LA ROCHELLE cedex
France	Novo Nordisk Investigational Site	Montigny-les-Metz
France	Novo Nordisk Investigational Site	Narbonne
France	Novo Nordisk Investigational Site	Nimes
France	Novo Nordisk Investigational Site	Sète
France	Novo Nordisk Investigational Site	Venissieux
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Debrecen
Hungary	Novo Nordisk Investigational Site	Nyíregyhaza
Hungary	Novo Nordisk Investigational Site	Székesfehérvár
Slovakia	Novo Nordisk Investigational Site	Bratislava
Slovakia	Novo Nordisk Investigational Site	Bratislava
Slovakia	Novo Nordisk Investigational Site	Bratislava
Slovakia	Novo Nordisk Investigational Site	Kosice
Slovakia	Novo Nordisk Investigational Site	Lucenec
Slovakia	Novo Nordisk Investigational Site	Nitra
Slovakia	Novo Nordisk Investigational Site	Presov
United States	Novo Nordisk Investigational Site	Altoona	Pennsylvania
United States	Novo Nordisk Investigational Site	Arlington	Texas
United States	Novo Nordisk Investigational Site	Arlington Heights	Illinois
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Austin	Texas
United States	Novo Nordisk Investigational Site	Berlin	New Jersey
United States	Novo Nordisk Investigational Site	Birmingham	Alabama
United States	Novo Nordisk Investigational Site	Bradenton	Florida
United States	Novo Nordisk Investigational Site	Chattanooga	Tennessee
United States	Novo Nordisk Investigational Site	Colorado Springs	Colorado
United States	Novo Nordisk Investigational Site	Columbus	Ohio
United States	Novo Nordisk Investigational Site	Concord	California
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dayton	Ohio
United States	Novo Nordisk Investigational Site	Encino	California
United States	Novo Nordisk Investigational Site	Fair Oaks	California
United States	Novo Nordisk Investigational Site	Flemington	New Jersey
United States	Novo Nordisk Investigational Site	Fort Myers	Florida
United States	Novo Nordisk Investigational Site	Fort Worth	Texas
United States	Novo Nordisk Investigational Site	Fresno	California
United States	Novo Nordisk Investigational Site	Goodyear	Arizona
United States	Novo Nordisk Investigational Site	Greenbrae	California
United States	Novo Nordisk Investigational Site	Hamilton	New Jersey
United States	Novo Nordisk Investigational Site	Henderson	Nevada
United States	Novo Nordisk Investigational Site	Honolulu	Hawaii
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Indianapolis	Indiana
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Jellico	Tennessee
United States	Novo Nordisk Investigational Site	Kalamazoo	Michigan
United States	Novo Nordisk Investigational Site	Kingsport	Tennessee
United States	Novo Nordisk Investigational Site	Lancaster	California
United States	Novo Nordisk Investigational Site	Las Vegas	Nevada
United States	Novo Nordisk Investigational Site	Lawrenceville	New Jersey
United States	Novo Nordisk Investigational Site	Lexington	Kentucky
United States	Novo Nordisk Investigational Site	Lomita	California
United States	Novo Nordisk Investigational Site	Long Beach	California
United States	Novo Nordisk Investigational Site	Mesa	Arizona
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Miami Springs	Florida
United States	Novo Nordisk Investigational Site	Mineola	New York
United States	Novo Nordisk Investigational Site	Montclair	California
United States	Novo Nordisk Investigational Site	Morehead City	North Carolina
United States	Novo Nordisk Investigational Site	Myrtle Beach	South Carolina
United States	Novo Nordisk Investigational Site	Nashua	New Hampshire
United States	Novo Nordisk Investigational Site	Nashville	Tennessee
United States	Novo Nordisk Investigational Site	North Massapequa	New York
United States	Novo Nordisk Investigational Site	Northridge	California
United States	Novo Nordisk Investigational Site	Omaha	Nebraska
United States	Novo Nordisk Investigational Site	Orem	Utah
United States	Novo Nordisk Investigational Site	Orlando	Florida
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania
United States	Novo Nordisk Investigational Site	Plano	Texas
United States	Novo Nordisk Investigational Site	Plant City	Florida
United States	Novo Nordisk Investigational Site	Reno	Nevada
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	Round Rock	Texas
United States	Novo Nordisk Investigational Site	Saint Charles	Missouri
United States	Novo Nordisk Investigational Site	Saint George	Utah
United States	Novo Nordisk Investigational Site	Salt Lake City	Utah
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	San Mateo	California
United States	Novo Nordisk Investigational Site	San Ramon	California
United States	Novo Nordisk Investigational Site	Schertz	Texas
United States	Novo Nordisk Investigational Site	Sugar Land	Texas
United States	Novo Nordisk Investigational Site	Sumter	South Carolina
United States	Novo Nordisk Investigational Site	Tarzana	California
United States	Novo Nordisk Investigational Site	Toms River	New Jersey
United States	Novo Nordisk Investigational Site	Troy	Michigan
United States	Novo Nordisk Investigational Site	Tullahoma	Tennessee
United States	Novo Nordisk Investigational Site	Van Nuys	California
United States	Novo Nordisk Investigational Site	West Seneca	New York
United States	Novo Nordisk Investigational Site	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Australia,  France,  Hungary,  Slovakia, 

References & Publications (2)

Lingvay I, Handelsman Y, Linjawi S, Vilsbøll T, Halladin N, Ranc K, Liebl A. EFFICACY AND SAFETY OF IDEGLIRA IN OLDER PATIENTS WITH TYPE 2 DIABETES. Endocr Pract. 2018 Nov 1. doi: 10.4158/EP-2018-0284. [Epub ahead of print] — View Citation

Linjawi S, Bode BW, Chaykin LB, Courrèges JP, Handelsman Y, Lehmann LM, Mishra A, Simpson RW. The Efficacy of IDegLira (Insulin Degludec/Liraglutide Combination) in Adults with Type 2 Diabetes Inadequately Controlled with a GLP-1 Receptor Agonist and Oral — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycosylated Haemoglobin (HbA1c) From Baseline (Randomisation, Visit 2)		Week 0, week 26
Secondary	Responders Achieving Pre-defined Target: HbA1c Below 7.0% (53 mmol/Mol)	Percentage of subjects achieving HbA1c below 7.0% after 26 weeks of treatment.	Week 26
Secondary	Responders Achieving Pre-defined Target: HbA1c Below or Equal to 6.5% (48 mmol/Mol)	Percentage of responders achieving pre-defined target for HbA1c - HbA1c = 6.5% (48 mmol/mol).	Week 26
Secondary	Change From Baseline in Body Weight	Mean change in body weight after 26 weeks of treatment.	Week 0, week 26
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG)	Mean change in fasting plasma glucose from baseline, after 26 weeks of treatment.	Week 0, week 26
Secondary	Number of Severe or Minor Hypoglycaemic Episodes	Rate (events per 100 patient years of exposure) of treatment-emergent confirmed hypoglycaemic episodes. The pool of severe and minor hypoglycaemic episodes was referred to as confirmed hypoglycaemic episodes. Severe hypoglycaemia was categorised as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as an episode with symptoms consistent with hypoglycaemia with confirmation by blood glucose <2.8 mmol/L (50 mg/dL) or PG <3.1 mmol/L (56 mg/dL), and which was handled by the subject himself/herself, or any asymptomatic blood glucose value <2.8 mmol/L (50 mg/dL) or PG value <3.1 mmol/L (56 mg/dL).	After 26 weeks of treatment
Secondary	Number of Adverse Events (AEs)	Rate (events per 100 exposure years) of treatment-emergent adverse events (an event that had onset date (or an increase in severity) on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment) which occurred during the 26 weeks of treatment.	After 26 weeks of treatment
Secondary	Change From Baseline in Patient Reported Outcomes (PROs) Based on the Treatment Related Impact Measure - Diabetes (TRIM-D)	The patient related outcome is calculated based on TRIM-D questionnaire. The TRIM-D questionnaire consists of 5 sub-domains (treatment burden, daily life, diabetes management, compliance and psychological health), where each question is scored to a 1-5-point scale with a higher score indicating a better health state (less negative impact). Mean TRIM-D individual sub-domain scores and total score are later transformed to a 0-100 scale for analysis. The mean change in scores from baseline to 26 weeks for all the individual sub domains and total scores are presented here.	Week 0, week 26
Secondary	Change From Baseline in Patient Reported Outcomes (PROs) Based on Diabetes Treatment Satisfaction Questionnaire (DTSQ).	Mean change in diabetes treatment satisfaction questionnaire (DTSQs) scores from baseline. The scores ranged from 0 to 6. Higher total score on a 0-6 point scale indicates a general higher treatment satisfaction, whereas higher score on perceived frequency of hyperglycaemia and perceived frequency of hypoglycaemia indicate that blood glucose levels are out of the target range.	Week 0, week 26

External Links

•   Clinical Trials at Novo Nordisk