The Effect of Liraglutide Versus Placebo When Added to Basal Insulin Analogues With or Without Metformin in Subjects With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01617434
First received: June 8, 2012
Last updated: October 31, 2014
Last verified: October 2014
Results First Received: October 22, 2014  
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: liraglutide
Drug: placebo

  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 76 sites in 9 countries i.e. 3 sites in Argentina; 9 sites in Canada; 5 sites in Finland; 9 sites in Germany; 9 sites in India; 2 sites in Mexico; 7 sites in Netherlands; 3 sites in Serbia; 29 sites in United States.

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
Liraglutide Liraglutide was administered subcutaneously (s.c. injection, under the skin) once daily (OD) for 26 weeks in combination with pre-trial basal insulin analogue regimen ± metformin. The starting dose of the liraglutide was 0.6 mg/day; dose was escalated to 1.2 mg/day after one week and 1.8 mg/day after 2 weeks; dose was maintained at 1.8 mg day for subsequent weeks until the end of the trial. All subjects continued their pre-trial insulin therapy of insulin glargine (100 U/mL, s.c. injection) or insulin detemir (100 U/mL, s.c. injection). Oral anti diabetic drug metformin was administered as a tablet with a total daily dose of ≥1500 mg, divided into one to three doses per day.
Placebo Placebo was administered subcutaneously (s.c. injection, under the skin) once daily (OD) for 26 weeks in combination with pre-trial basal insulin analogue regimen ± metformin. The starting dose of the placebo was 0.6 mg/day; dose was escalated to 1.2 mg/day after one week and 1.8 mg/day after 2 weeks; dose was maintained at 1.8 mg day for subsequent weeks until the end of the trial. All subjects continued their pre-trial insulin therapy of insulin glargine (100 U/mL, s.c. injection) or insulin detemir (100 U/mL, s.c. injection). Oral anti diabetic drug metformin was administered as a tablet with a total daily dose of ≥1500 mg, divided into one to three doses per day.

Participant Flow:   Overall Study
    Liraglutide     Placebo  
STARTED     226     225  
Exposed     225     225  
COMPLETED     191     174  
NOT COMPLETED     35     51  
Adverse Event                 12                 3  
Protocol Violation                 8                 7  
Withdrawal Criteria                 12                 37  
Unclassified                 3                 4  



  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
Liraglutide Liraglutide was administered subcutaneously (s.c. injection, under the skin) once daily (OD) for 26 weeks in combination with pre-trial basal insulin analogue regimen ± metformin. The starting dose of the liraglutide was 0.6 mg/day; dose was escalated to 1.2 mg/day after one week and 1.8 mg/day after 2 weeks; dose was maintained at 1.8 mg day for subsequent weeks until the end of the trial. All subjects continued their pre-trial insulin therapy of insulin glargine (100 U/mL, s.c. injection) or insulin detemir (100 U/mL, s.c. injection). Oral anti diabetic drug metformin was administered as a tablet with a total daily dose of ≥1500 mg, divided into one to three doses per day.
Placebo Placebo was administered subcutaneously (s.c. injection, under the skin) once daily (OD) for 26 weeks in combination with pre-trial basal insulin analogue regimen ± metformin. The starting dose of the placebo was 0.6 mg/day; dose was escalated to 1.2 mg/day after one week and 1.8 mg/day after 2 weeks; dose was maintained at 1.8 mg day for subsequent weeks until the end of the trial. All subjects continued their pre-trial insulin therapy of insulin glargine (100 U/mL, s.c. injection) or insulin detemir (100 U/mL, s.c. injection). Oral anti diabetic drug metformin was administered as a tablet with a total daily dose of ≥1500 mg, divided into one to three doses per day.
Total Total of all reporting groups

Baseline Measures
    Liraglutide     Placebo     Total  
Number of Participants  
[units: participants]
  225     225     450  
Age  
[units: years]
Mean (Standard Deviation)
  59.3  (9.2)     57.5  (11.1)     58.4  (10.2)  
Gender  
[units: participants]
     
Female     105     89     194  
Male     120     136     256  
Body Weight  
[units: kg]
Mean (Standard Deviation)
  90.23  (19.98)     91.85  (21.33)     91.04  (20.66)  
Fasting Plasma Glucose (FPG)  
[units: mmol/L]
Mean (Standard Deviation)
  8.32  (2.89)     8.21  (2.90)     8.27  (2.89)  
Glycosylated Haemoglobin (HbA1c)  
[units: percentage of glycosylated haemoglobin]
Mean (Standard Deviation)
  8.22  (0.81)     8.28  (0.90)     8.25  (0.86)  



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

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

3.  Secondary:   Change in Mean Self-Measured Plasma Glucose (SMPG) of 7-Point Profile From Baseline to Week 26   [ Time Frame: Week 0 to Week 26 ]

4.  Secondary:   Change in Body Weight From Baseline to Week 26   [ Time Frame: Week 0 to Week 26 ]

5.  Secondary:   Number of Subjects Achieving HbA1c Below 7.0% (American Diabetes Association [ADA] Target)   [ Time Frame: At Week 26 ]

6.  Secondary:   Number of Subjects Achieving HbA1c Below or Equal to 6.5% (American Association of Clinical Endocrinologists [AACE] Target)   [ Time Frame: At Week 26 ]

7.  Secondary:   Number of Adverse Events (AEs) During The Randomised Treatment Period   [ Time Frame: Week 0 to Week 26 + 7 days follow up ]

8.  Secondary:   Number of Minor Hypoglycaemic Episodes During The Randomised Treatment Period   [ Time Frame: Week 0 to Week 26 + 7 days follow up ]

9.  Secondary:   Number of Severe Hypoglycaemic Episodes During The Randomised Treatment Period   [ Time Frame: Week 0 to Week 26 + 7 days follow up ]


  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


No publications provided


Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01617434     History of Changes
Other Study ID Numbers: NN2211-3917, 2011-002696-41, U1111-1121-9874
Study First Received: June 8, 2012
Results First Received: October 22, 2014
Last Updated: October 31, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia
Canada: Health Canada
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
India: Ministry of Health and Family Wellfare
Mexico: National Institute of Public Health, Health Secretariat
Netherlands: Medicines Evaluation Board, Dutch Health Care Inspectorate
Serbia: Medicines and Medical Devices Agency of Serbia
United States: Food and Drug Administration