The Efficacy and Safety of Liraglutide Adjunct to Insulin Treatment in Type 1 Diabetes (ADJUNCT TWO™)

December 15, 2016 updated by: Novo Nordisk A/S

A 26-weeks Randomised, Insulin Capped, Placebo-controlled, Double-blind, Parallel Group, Multinational, Multi-centre Trial

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.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

835

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Graz, Austria, 8036
        • Novo Nordisk INvestigational Site
      • Wien, Austria, 1130
        • Novo Nordisk INvestigational Site
      • Aalst, Belgium, 9300
        • Novo Nordisk INvestigational Site
      • Bonheiden, Belgium, 2820
        • Novo Nordisk INvestigational Site
      • Boussu, Belgium, 7300
        • Novo Nordisk INvestigational Site
      • Brussels, Belgium, 1090
        • Novo Nordisk INvestigational Site
      • Bruxelles, Belgium, 1200
        • Novo Nordisk INvestigational Site
      • Edegem, Belgium, 2650
        • Novo Nordisk INvestigational Site
      • Kortrijk, Belgium, 8500
        • Novo Nordisk INvestigational Site
      • Leuven, Belgium, 3000
        • Novo Nordisk INvestigational Site
      • Mouscron, Belgium, 7700
        • Novo Nordisk INvestigational Site
      • Sint-Niklaas, Belgium, 9100
        • Novo Nordisk INvestigational Site
      • Blagoevgrad, Bulgaria, 2700
        • Novo Nordisk INvestigational Site
      • Pazardzhik, Bulgaria, 4401
        • Novo Nordisk INvestigational Site
      • Plovdiv, Bulgaria, 4002
        • Novo Nordisk INvestigational Site
      • Razgrad, Bulgaria, 7200
        • Novo Nordisk INvestigational Site
      • Sofia, Bulgaria, 1431
        • Novo Nordisk INvestigational Site
    • Alberta
      • Calgary, Alberta, Canada, T2V 4J2
        • Novo Nordisk INvestigational Site
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • Novo Nordisk INvestigational Site
    • Ontario
      • Cornwall, Ontario, Canada, K6H 4M4
        • Novo Nordisk INvestigational Site
      • Hamilton, Ontario, Canada, L8N 3Z5
        • Novo Nordisk INvestigational Site
      • Mississauga, Ontario, Canada, L5M 2V8
        • Novo Nordisk INvestigational Site
      • Thornhill, Ontario, Canada, L4J 8L7
        • Novo Nordisk INvestigational Site
    • Quebec
      • Laval, Quebec, Canada, H7T 2P5
        • Novo Nordisk INvestigational Site
      • Montreal, Quebec, Canada, H2X 0A9
        • Novo Nordisk INvestigational Site
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Novo Nordisk INvestigational Site
      • Hvidovre, Denmark, 2650
        • Novo Nordisk INvestigational Site
      • København, Denmark, 2400
        • Novo Nordisk INvestigational Site
      • Odense, Denmark, 5000
        • Novo Nordisk INvestigational Site
      • Århus C, Denmark, 8000
        • Novo Nordisk INvestigational Site
      • Helsinki, Finland, 00250
        • Novo Nordisk INvestigational Site
      • Joensuu, Finland, 80200
        • Novo Nordisk INvestigational Site
      • Jyväskylä, Finland, 40620
        • Novo Nordisk INvestigational Site
      • Oulu, Finland, FI-90220
        • Novo Nordisk INvestigational Site
      • Pori, Finland, 28500
        • Novo Nordisk INvestigational Site
      • Turku, Finland, FI-20520
        • Novo Nordisk INvestigational Site
      • LA ROCHELLE cedex, France, 17019
        • Novo Nordisk INvestigational Site
      • Le Creusot, France, 71200
        • Novo Nordisk INvestigational Site
      • MARSEILLE cedex 08, France, 13285
        • Novo Nordisk INvestigational Site
      • MONTPELLIER cedex 5, France, 34295
        • Novo Nordisk INvestigational Site
      • Paris, France, 75014
        • Novo Nordisk INvestigational Site
      • Pierre-Bénite, France, 69495
        • Novo Nordisk INvestigational Site
      • Reims, France, 51100
        • Novo Nordisk INvestigational Site
      • Strasbourg, France, 67098
        • Novo Nordisk INvestigational Site
      • TOULOUSE cedex, France, 31054
        • Novo Nordisk INvestigational Site
      • Trinité - La Martinique, France, 97235
        • Novo Nordisk INvestigational Site
      • Bergamo, Italy, 24127
        • Novo Nordisk INvestigational Site
      • Catanzaro, Italy, 88100
        • Novo Nordisk INvestigational Site
      • Firenze, Italy, 50141
        • Novo Nordisk INvestigational Site
      • Palermo, Italy, 90127
        • Novo Nordisk INvestigational Site
      • Roma, Italy, 00133
        • Novo Nordisk INvestigational Site
      • Roma, Italy, 00168
        • Novo Nordisk INvestigational Site
      • Siena, Italy, 53100
        • Novo Nordisk INvestigational Site
      • sesto san giovanni (MI), Italy, 20099
        • Novo Nordisk INvestigational Site
      • Amersfoort, Netherlands, 3813 TZ
        • Novo Nordisk INvestigational Site
      • Apeldoorn, Netherlands, 7334 DZ
        • Novo Nordisk INvestigational Site
      • Den Bosch, Netherlands, 5223GZ
        • Novo Nordisk INvestigational Site
      • Den Haag, Netherlands, 2597 AX
        • Novo Nordisk INvestigational Site
      • Eindhoven, Netherlands, 5631 BM
        • Novo Nordisk INvestigational Site
      • Utrecht, Netherlands, 3584 CX
        • Novo Nordisk INvestigational Site
    • Gauteng
      • Johannesburg, Gauteng, South Africa, 2198
        • Novo Nordisk INvestigational Site
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7925
        • Novo Nordisk INvestigational Site
      • Almería, Spain, 04001
        • Novo Nordisk INvestigational Site
      • Gijón, Spain, 33206
        • Novo Nordisk INvestigational Site
      • Segovia, Spain, 40002
        • Novo Nordisk INvestigational Site
      • Sevilla, Spain, 41010
        • Novo Nordisk INvestigational Site
      • Sevilla, Spain, 41014
        • Novo Nordisk INvestigational Site
      • Linköping, Sweden, 582 16
        • Novo Nordisk INvestigational Site
      • Malmö, Sweden, 205 02
        • Novo Nordisk INvestigational Site
      • Stockholm, Sweden, 112 81
        • Novo Nordisk INvestigational Site
      • Umeå, Sweden, 901 85
        • Novo Nordisk INvestigational Site
      • Ängelholm, Sweden, 262 91
        • Novo Nordisk INvestigational Site
      • Örebro, Sweden, 701 85
        • Novo Nordisk INvestigational Site
    • Arizona
      • Phoenix, Arizona, United States, 85032
        • Novo Nordisk INvestigational Site
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Novo Nordisk INvestigational Site
    • California
      • Concord, California, United States, 94520
        • Novo Nordisk INvestigational Site
      • Escondido, California, United States, 92025
        • Novo Nordisk INvestigational Site
      • Fresno, California, United States, 93720
        • Novo Nordisk INvestigational Site
      • Montclair, California, United States, 91763
        • Novo Nordisk INvestigational Site
      • San Mateo, California, United States, 94401
        • Novo Nordisk INvestigational Site
      • San Ramon, California, United States, 94583
        • Novo Nordisk INvestigational Site
      • Ventura, California, United States, 93003
        • Novo Nordisk INvestigational Site
      • Walnut Creek, California, United States, 94598
        • Novo Nordisk INvestigational Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Novo Nordisk INvestigational Site
      • Golden, Colorado, United States, 80401
        • Novo Nordisk INvestigational Site
    • Florida
      • Maitland, Florida, United States, 32751
        • Novo Nordisk INvestigational Site
    • Georgia
      • Atlanta, Georgia, United States, 30318
        • Novo Nordisk INvestigational Site
      • Marietta, Georgia, United States, 30060
        • Novo Nordisk INvestigational Site
      • Roswell, Georgia, United States, 30076
        • Novo Nordisk INvestigational Site
    • Illinois
      • Champaign, Illinois, United States, 61821
        • Novo Nordisk INvestigational Site
      • Chicago, Illinois, United States, 60611
        • Novo Nordisk INvestigational Site
      • Skokie, Illinois, United States, 60077
        • Novo Nordisk INvestigational Site
    • Iowa
      • Council Bluffs, Iowa, United States, 51501
        • Novo Nordisk INvestigational Site
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • Novo Nordisk INvestigational Site
    • Maryland
      • Rockville, Maryland, United States, 20852
        • Novo Nordisk INvestigational Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55416
        • Novo Nordisk INvestigational Site
    • Missouri
      • Chesterfield, Missouri, United States, 63017
        • Novo Nordisk INvestigational Site
    • Montana
      • Billings, Montana, United States, 59101
        • Novo Nordisk INvestigational Site
      • Butte, Montana, United States, 59701
        • Novo Nordisk INvestigational Site
    • Nevada
      • Las Vegas, Nevada, United States, 89128
        • Novo Nordisk INvestigational Site
    • New York
      • Albany, New York, United States, 12206
        • Novo Nordisk INvestigational Site
      • Jamaica, New York, United States, 11432-1121
        • Novo Nordisk INvestigational Site
      • Staten Island, New York, United States, 10301
        • Novo Nordisk INvestigational Site
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27517
        • Novo Nordisk INvestigational Site
      • Morehead City, North Carolina, United States, 28557
        • Novo Nordisk INvestigational Site
      • Wilmington, North Carolina, United States, 28401
        • Novo Nordisk INvestigational Site
    • North Dakota
      • Fargo, North Dakota, United States, 58103
        • Novo Nordisk INvestigational Site
    • Tennessee
      • Bristol, Tennessee, United States, 37620-7352
        • Novo Nordisk INvestigational Site
      • Chattanooga, Tennessee, United States, 37411
        • Novo Nordisk INvestigational Site
    • Texas
      • Amarillo, Texas, United States, 79106
        • Novo Nordisk INvestigational Site
      • Austin, Texas, United States, 78758
        • Novo Nordisk INvestigational Site
      • Dallas, Texas, United States, 75230
        • Novo Nordisk INvestigational Site
      • Dallas, Texas, United States, 75231
        • Novo Nordisk INvestigational Site
      • Round Rock, Texas, United States, 78681
        • Novo Nordisk INvestigational Site
    • Utah
      • Murray, Utah, United States, 84123
        • Novo Nordisk INvestigational Site
      • Ogden, Utah, United States, 84405
        • Novo Nordisk INvestigational Site
    • Vermont
      • Bennington, Vermont, United States, 05201
        • Novo Nordisk INvestigational Site
    • Washington
      • Federal Way, Washington, United States, 98003
        • Novo Nordisk INvestigational Site
      • Renton, Washington, United States, 98057
        • Novo Nordisk INvestigational Site
      • Seattle, Washington, United States, 98195
        • Novo Nordisk INvestigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Liraglutide 1.8 mg + insulin
Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment will receive 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects will receive 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.
Experimental: Liraglutide 1.2 mg + insulin
Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment will receive 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects will receive 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.
Experimental: Liraglutide 0.6 mg + insulin
Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment will receive 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects will receive 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.
Placebo Comparator: Liraglutide placebo 0.3 ml + insulin
Subjects randomised to 0.3 mL liraglutide placebo as an add-on to their pre-trial insulin treatment will receive 0.1 mL for 2 weeks followed by 0.2 mL for 2 weeks. After 4 weeks of liraglutide placebo, subjects will receive 0.3 mL for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.
Placebo Comparator: Liraglutide placebo 0.2 ml + insulin
Subjects randomised to 0.3 mL liraglutide placebo as an add-on to their pre-trial insulin treatment will receive 0.1 mL for 2 weeks followed by 0.2 mL for 2 weeks. After 4 weeks of liraglutide placebo, subjects will receive 0.3 mL for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.
Placebo Comparator: Liraglutide placebo 0.1 ml + insulin
Subjects randomised to 0.3 mL liraglutide placebo as an add-on to their pre-trial insulin treatment will receive 0.1 mL for 2 weeks followed by 0.2 mL for 2 weeks. After 4 weeks of liraglutide placebo, subjects will receive 0.3 mL for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Glycosylated Haemoglobin (HbA1c)
Time Frame: Week 0, Week 26
Change from baseline in glycosylated haemoglobin (HbA1c), after 26 weeks of treatment. Full analysis set (FAS = 831) included all randomised subjects who had received at least one dose and had any post-randomisation data.
Week 0, Week 26

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Body Weight
Time Frame: Week 0, Week 26
Change from baseline body weight, after 26 weeks of treatment. Full analysis set (FAS = 831) included all randomised subjects who had received at least one dose and had any post-randomisation data.
Week 0, Week 26
Number of Treatment-emergent Symptomatic Hypoglycaemic Episodes
Time Frame: Weeks 0-26
Number of treatment-emergent symptomatic hypoglycaemic episodes during 26 weeks of treatment. Symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification or a self-measured plasma glucose (SMPG) value of <3.1 mmol/L (56 mg/dL), with symptoms consistent with hypoglycaemia. Severe hypoglycaemia as per ADA classification is defined as an episode that required assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions.
Weeks 0-26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2014

Primary Completion (Actual)

April 1, 2015

Study Completion (Actual)

April 1, 2015

Study Registration Dates

First Submitted

March 25, 2014

First Submitted That Met QC Criteria

March 25, 2014

First Posted (Estimate)

March 28, 2014

Study Record Updates

Last Update Posted (Estimate)

February 9, 2017

Last Update Submitted That Met QC Criteria

December 15, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Other Study ID Numbers

  • NN9211-4083
  • 2012-005778-74 (EudraCT Number)
  • U1111-1138-0619 (Other Identifier: WHO)
  • NL47705.060.14 (Registry Identifier: CCMO)
  • REec-2014-0884 (Registry Identifier: Spanish registry)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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