Clinical trial NCT02098395: The Efficacy and Safety of Liraglutide Adjunct to Insulin Treatment in Type 1 Diabetes
Official title: A 26-weeks Randomised, Insulin Capped, Placebo-controlled, Double-blind, Parallel Group, Multinational, Multi-centre Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 1
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2014-03-28
Enrollment: 835
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Africa, Europe and North America. The purpose of the trial is to investigate the efficacy and safety of liraglutide adjunct to insulin treatment in type 1 diabetes.


Eligibility criteria: Inclusion Criteria:

* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
* Male or female, aged equal to or greater than 18 years at the time of signing informed consent
* Type 1 diabetes mellitus (as diagnosed clinically) 12 months or longer prior to Visit 1 (i.e. screening)
* Treatment with basal bolus or CSII (continuous subcutaneous insulin infusion, insulin pump) treatment 6 months or longer prior to Visit 1 (i.e. screening)
* Stable insulin treatment 3 months or longer prior to Visit 1 (i.e. screening), as judged and documented by the investigator
* HbA1c 7.0-10.0 percent (Diabetes Control and Complications Trial (DCCT)), both inclusive, by central laboratory analysis (Visit 1, screening) corresponding to 53-86 mmol/mol (International Federation of Clinical Chemistry (IFCC))

Exclusion Criteria:

* Prior use of glucagon-like peptide-1 (GLP-1) receptor agonist or dipeptidyl peptidase IV (DPPIV) inhibitors
* Use of any medication, which in the investigator's opinion could interfere with the glycaemic control (e.g. systemic corticosteroids, pramlintide (Symlin®)) or affect the subject's safety. Premix insulin is not allowed
* Known proliferative retinopathy or maculopathy requiring acute treatment
* Severe neuropathy, in particular autonomic neuropathy, i.e. gastroparesis, as judged by the investigator
* Uncontrolled/untreated blood pressure at screening (Visit 1) (after resting for 5 minutes) while sitting greater than 160 mmHg for systolic or greater than 100 mmHg for diastolic (repeated measurement at Visit 2 (prior to performing the trial related activities) is allowed to exclude white-coat hypertension)
* History of acute or chronic pancreatitis
* Screening (Visit 1) calcitonin value equal to or greater than 50 ng/L

Primary outcomes:
measure: Change From Baseline in Glycosylated Haemoglobin (HbA1c)
timeFrame: Week 0, Week 26
Secondary outcomes:
measure: Change From Baseline in Body Weight
timeFrame: Week 0, Week 26
measure: Number of Treatment-emergent Symptomatic Hypoglycaemic Episodes
timeFrame: Weeks 0-26
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Little Rock
country: United States
facility: Novo Nordisk Investigational Site
state: Arkansas
city: Concord
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Escondido
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Fresno
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Montclair
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Mateo
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Ramon
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Ventura
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Aurora
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Golden
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Maitland
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Marietta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Roswell
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Champaign
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Skokie
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Council Bluffs
country: United States
facility: Novo Nordisk Investigational Site
state: Iowa
city: Lexington
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Rockville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Minneapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: Chesterfield
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: Billings
country: United States
facility: Novo Nordisk Investigational Site
state: Montana
city: Butte
country: United States
facility: Novo Nordisk Investigational Site
state: Montana
city: Las Vegas
country: United States
facility: Novo Nordisk Investigational Site
state: Nevada
city: Albany
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Jamaica
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Staten Island
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Morehead City
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Fargo
country: United States
facility: Novo Nordisk Investigational Site
state: North Dakota
city: Bristol
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Amarillo
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Austin
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Round Rock
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Murray
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Ogden
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Bennington
country: United States
facility: Novo Nordisk Investigational Site
state: Vermont
city: Federal Way
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Renton
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Seattle
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Graz
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Aalst
country: Belgium
facility: Novo Nordisk Investigational Site
city: Bonheiden
country: Belgium
facility: Novo Nordisk Investigational Site
city: Boussu
country: Belgium
facility: Novo Nordisk Investigational Site
city: Brussels
country: Belgium
facility: Novo Nordisk Investigational Site
city: Bruxelles
country: Belgium
facility: Novo Nordisk Investigational Site
city: Edegem
country: Belgium
facility: Novo Nordisk Investigational Site
city: Kortrijk
country: Belgium
facility: Novo Nordisk Investigational Site
city: Leuven
country: Belgium
facility: Novo Nordisk Investigational Site
city: Mouscron
country: Belgium
facility: Novo Nordisk Investigational Site
city: Sint-Niklaas
country: Belgium
facility: Novo Nordisk Investigational Site
city: Blagoevgrad
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Pazardzhik
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Plovdiv
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Razgrad
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Calgary
country: Canada
facility: Novo Nordisk Investigational Site
state: Alberta
city: Halifax
country: Canada
facility: Novo Nordisk Investigational Site
state: Nova Scotia
city: Cornwall
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Hamilton
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Thornhill
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Laval
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Hvidovre
country: Denmark
facility: Novo Nordisk Investigational Site
city: København
country: Denmark
facility: Novo Nordisk Investigational Site
city: Odense
country: Denmark
facility: Novo Nordisk Investigational Site
city: Århus C
country: Denmark
facility: Novo Nordisk Investigational Site
city: Helsinki
country: Finland
facility: Novo Nordisk Investigational Site
city: Joensuu
country: Finland
facility: Novo Nordisk Investigational Site
city: Jyväskylä
country: Finland
facility: Novo Nordisk Investigational Site
city: Oulu
country: Finland
facility: Novo Nordisk Investigational Site
city: Pori
country: Finland
facility: Novo Nordisk Investigational Site
city: Turku
country: Finland
facility: Novo Nordisk Investigational Site
city: LA ROCHELLE cedex
country: France
facility: Novo Nordisk Investigational Site
city: Le Creusot
country: France
facility: Novo Nordisk Investigational Site
city: MARSEILLE cedex 08
country: France
facility: Novo Nordisk Investigational Site
city: MONTPELLIER cedex 5
country: France
facility: Novo Nordisk Investigational Site
city: Paris
country: France
facility: Novo Nordisk Investigational Site
city: Pierre-Bénite
country: France
facility: Novo Nordisk Investigational Site
city: Reims
country: France
facility: Novo Nordisk Investigational Site
city: Strasbourg
country: France
facility: Novo Nordisk Investigational Site
city: TOULOUSE cedex
country: France
facility: Novo Nordisk Investigational Site
city: Trinité - La Martinique
country: France
facility: Novo Nordisk Investigational Site
city: Bergamo
country: Italy
facility: Novo Nordisk Investigational Site
city: Catanzaro
country: Italy
facility: Novo Nordisk Investigational Site
city: Firenze
country: Italy
facility: Novo Nordisk Investigational Site
city: Palermo
country: Italy
facility: Novo Nordisk Investigational Site
city: Roma
country: Italy
facility: Novo Nordisk Investigational Site
city: Roma
country: Italy
facility: Novo Nordisk Investigational Site
city: sesto san giovanni (MI)
country: Italy
facility: Novo Nordisk Investigational Site
city: Siena
country: Italy
facility: Novo Nordisk Investigational Site
city: Amersfoort
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Apeldoorn
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Den Bosch
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Den Haag
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Eindhoven
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Utrecht
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Johannesburg
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Cape Town
country: South Africa
facility: Novo Nordisk Investigational Site
state: Western Cape
city: Almería
country: Spain
facility: Novo Nordisk Investigational Site
city: Gijón
country: Spain
facility: Novo Nordisk Investigational Site
city: Segovia
country: Spain
facility: Novo Nordisk Investigational Site
city: Sevilla
country: Spain
facility: Novo Nordisk Investigational Site
city: Sevilla
country: Spain
facility: Novo Nordisk Investigational Site
city: Linköping
country: Sweden
facility: Novo Nordisk Investigational Site
city: Malmö
country: Sweden
facility: Novo Nordisk Investigational Site
city: Stockholm
country: Sweden
facility: Novo Nordisk Investigational Site
city: Umeå
country: Sweden
facility: Novo Nordisk Investigational Site
city: Ängelholm
country: Sweden
facility: Novo Nordisk Investigational Site
city: Örebro
country: Sweden
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Ahren B, Hirsch IB, Pieber TR, Mathieu C, Gomez-Peralta F, Hansen TK, Philotheou A, Birch S, Christiansen E, Jensen TJ, Buse JB; ADJUNCT TWO Investigators. Efficacy and Safety of Liraglutide Added to Capped Insulin Treatment in Subjects With Type 1 Diabetes: The ADJUNCT TWO Randomized Trial. Diabetes Care. 2016 Oct;39(10):1693-701. doi: 10.2337/dc16-0690. Epub 2016 Aug 4.
citation: Hoogenhout M, Malcolm-Smith S. Theory of mind predicts severity level in autism. Autism. 2017 Feb;21(2):242-252. doi: 10.1177/1362361316636758. Epub 2016 Aug 19.
citation: Dejgaard TF, von Scholten BJ, Christiansen E, Kreiner FF, Bardtrum L, von Herrath M, Mathieu C, Madsbad S; ADJUNCT ONE and ADJUNCT TWO Investigators. Efficacy and safety of liraglutide in type 1 diabetes by baseline characteristics in the ADJUNCT ONE and ADJUNCT TWO randomized controlled trials. Diabetes Obes Metab. 2021 Dec;23(12):2752-2762. doi: 10.1111/dom.14532. Epub 2021 Sep 28.