The Effect of Insulin Degludec in Combination With Liraglutide and Metformin in Subjects With Type 2 Diabetes Qualifying for Treatment Intensification

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01664247
First received: August 10, 2012
Last updated: March 18, 2016
Last verified: March 2016
Results First Received: October 23, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Diabetes
Diabetes Mellitus, Type 2
Interventions: Drug: insulin degludec
Drug: placebo
Drug: liraglutide

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The trial was conducted at 129 sites in 11 countries randomised subjects: Canada (7), France (10), Germany (8), Israel (6), Italy (7), Serbia (7), South Africa (6), Ukraine (4), United Arab Emirates (3), United Kingdom (6), and United States (65).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
IDeg Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Placebo Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.

Participant Flow:   Overall Study
    IDeg     Placebo  
STARTED     174     172  
Exposed     173 [1]   170 [2]
COMPLETED     160     131  
NOT COMPLETED     14     41  
Adverse Event                 5                 3  
Protocol Violation                 3                 5  
Withdrawal Criteria                 1                 4  
Unclassified                 5                 29  
[1] 1 subject was randomised in error and withdrew before exposure to the drug
[2] Two subjects were randomised in error and withdrew prior to exposure to drug



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
IDeg Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Placebo Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Total Total of all reporting groups

Baseline Measures
    IDeg     Placebo     Total  
Number of Participants  
[units: participants]
  174     172     346  
Age  
[units: years]
Mean (Standard Deviation)
  57.0  (10.0)     57.3  (9.4)     57.2  (9.7)  
Gender  
[units: participants]
     
Female     76     68     144  
Male     98     104     202  
Glycosylated haemoglobin (HbA1c)  
[units: percentage¬†of¬†glycosylated¬†haemoglobin]
Mean (Standard Deviation)
  7.5  (0.6)     7.6  (0.6)     7.6  (0.6)  
Fasting plasma glucose (FPG)  
[units: mmol/L]
Mean (Standard Deviation)
  8.7  (2.1)     9.1  (2.2)     8.9  (2.2)  



  Outcome Measures
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1.  Primary:   Change From Baseline in Glycosylated Haemoglobin (HbA1c) (%)   [ Time Frame: Week 0, week 26 ]

2.  Secondary:   Change From Baseline in Fasting Plasma Glucose (FPG)   [ Time Frame: Week 0, week 26 ]

3.  Secondary:   Number of Responders for HbA1c (Below 7.0 %)   [ Time Frame: After 26 weeks of randomised treatment. ]

4.  Secondary:   Change From Baseline in Mean Pre-breakfast Measurements Used for Titration   [ Time Frame: Week 0, week 26 ]

5.  Secondary:   Change From Baseline in 8-point Profile   [ Time Frame: Week 0, week 26 ]

6.  Secondary:   Change From Baseline in Mean of the 8-point Profile   [ Time Frame: Week 0, week 26 ]

7.  Secondary:   Number of Hypoglycaemic Episodes   [ Time Frame: Weeks 0 - 26 ]

8.  Secondary:   Number of Adverse Events   [ Time Frame: Weeks 0 - 26 ]

9.  Secondary:   Change From Baseline in Patient Reported Health-related Quality of Life Using the Short-Form 36 Health Survey Version 2 (SF-36®v2)   [ Time Frame: Week 0, week 26 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
e-mail: clinicaltrials@novonordisk.com



Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01664247     History of Changes
Other Study ID Numbers: NN1250-3944
2011-004665-32 ( EudraCT Number )
U1111-1124-6612 ( Other Identifier: WHO )
Study First Received: August 10, 2012
Results First Received: October 23, 2015
Last Updated: March 18, 2016
Health Authority: Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Israel: Ministry of Health
Italy: Ministry of Health
Serbia: Medicines and Medical Devices Agency of Serbia
South Africa: Medicines Control Council
Ukraine: Ministry of Health Ukraine
United Arab Emirates: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration