Safety and Efficacy of Liraglutide in Combination With an OAD in Subjects With Type 2 Diabetes Insufficiently Controlled on OAD Alone

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01512108
First received: January 10, 2012
Last updated: April 25, 2014
Last verified: April 2014
Results First Received: April 25, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Diabetes
Diabetes Mellitus, Type 2
Interventions: Drug: liraglutide
Drug: oral anti-diabetic drug

  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 36 sites in Japan.

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 0.9 mg/Day Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.
Additional OAD Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual’s glycaemic control by the investigator as per Japanese labelling.

Participant Flow:   Overall Study
    Liraglutide 0.9 mg/Day     Additional OAD  
STARTED     243     120  
Exposed     240 [1]   120  
COMPLETED     221     111  
NOT COMPLETED     22     9  
Adverse Event                 9                 4  
Protocol Violation                 1                 2  
Withdrawal Criteria                 1                 0  
Unclassified                 11                 3  
[1] 3 subjects withdrew prior to exposure to trial 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
Liraglutide 0.9 mg/Day Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.
Additional OAD Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual’s glycaemic control by the investigator as per Japanese labelling.
Total Total of all reporting groups

Baseline Measures
    Liraglutide 0.9 mg/Day     Additional OAD     Total  
Number of Participants  
[units: participants]
  240     120     360  
Age  
[units: years]
Mean ± Standard Deviation
  59.6  ± 11.6     59.2  ± 10.2     59.5  ± 11.1  
Gender  
[units: participants]
     
Female     58     40     98  
Male     182     80     262  
Glycosylated haemoglobin (HbA1c)  
[units: percentage of glycosylated haemoglobin]
Mean ± Standard Deviation
  8.1  ± 0.8     8.1  ± 0.8     8.1  ± 0.8  
Fasting plasma glucose (FPG)  
[units: mmol/L]
Mean ± Standard Deviation
  8.68  ± 1.61     8.96  ± 1.82     8.77  ± 1.69  



  Outcome Measures
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1.  Primary:   Incidence of Treatment Emergent Adverse Events (AEs)   [ Time Frame: Week 0 to Week 52 + 7 days ]

Measure Type Primary
Measure Title Incidence of Treatment Emergent Adverse Events (AEs)
Measure Description Adverse events were defined as events occurring after administration of trial product and no later than 7 days after last day of treatment. Severe AEs: considerable interference with subject's daily activities. Moderate AEs: Marked symptoms, moderate interference with the subject's daily activities. Mild AEs: No or transient symptoms, no interference with the subject's daily activities. Serious AEs: AEs that resulted in any of the following: death, a life-threatening experience, hospitalization/prolongation of existing hospitalization, persistent/significant disability, and congenital anomaly.
Time Frame Week 0 to Week 52 + 7 days  
Safety Issue No  

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.
Safety analysis set included all subjects who received at least one dose of the trial product.

Reporting Groups
  Description
Liraglutide 0.9 mg/Day Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.
Additional OAD Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual’s glycaemic control by the investigator as per Japanese labelling.

Measured Values
    Liraglutide 0.9 mg/Day     Additional OAD  
Number of Participants Analyzed  
[units: participants]
  240     120  
Incidence of Treatment Emergent Adverse Events (AEs)  
[units: Events/100 years of patient exposure]
   
All AEs     361     331  
Mild AEs     345     321  
Moderate AEs     14     9  
Severe AEs     2     2  
Serious AEs     5     9  

No statistical analysis provided for Incidence of Treatment Emergent Adverse Events (AEs)



2.  Secondary:   Number of Confirmed Hypoglycaemic Episodes   [ Time Frame: Week 0 to Week 52 ]

Measure Type Secondary
Measure Title Number of Confirmed Hypoglycaemic Episodes
Measure Description Confirmed hypoglycaemic episodes consisted of the pool of episodes of severe hypoglycaemia as well as minor hypoglycaemic episodes [An episode with symptoms consistent with hypoglycaemia with confirmation by plasma glucose <3.1 mmol/L (56 mg/dL) or full blood glucose <2.8 mmol/L (50 mg/dL) and which is handled by the subject himself or herself or any asymptomatic PG value <3.1 mmol/L (56 mg/dL) or full blood glucose value <2.8 mmol/L (50 mg/dL)] with a confirmed plasma glucose value of less than 3.1 mmol/L (56 mg/dL).
Time Frame Week 0 to Week 52  
Safety Issue No  

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.
Safety analysis set includes all subjects who received at least one dose of the trial product.

Reporting Groups
  Description
Liraglutide 0.9 mg/Day Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.
Additional OAD Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual’s glycaemic control by the investigator as per Japanese labelling.

Measured Values
    Liraglutide 0.9 mg/Day     Additional OAD  
Number of Participants Analyzed  
[units: participants]
  240     120  
Number of Confirmed Hypoglycaemic Episodes  
[units: episodes]
  7     2  

No statistical analysis provided for Number of Confirmed Hypoglycaemic Episodes



3.  Secondary:   Change in HbA1c From Baseline to Week 52   [ Time Frame: Week 0, week 52 ]

Measure Type Secondary
Measure Title Change in HbA1c From Baseline to Week 52
Measure Description Estimated mean change in HbA1c from baseline after 52 Weeks of treatment
Time Frame Week 0, week 52  
Safety Issue No  

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.
Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products and missing data were imputed using last observation carried forward (LOCF). One subject did not contribute to the statistical analysis at Week 52.

Reporting Groups
  Description
Liraglutide 0.9 mg/Day Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.
Additional OAD Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual’s glycaemic control by the investigator as per Japanese labelling.

Measured Values
    Liraglutide 0.9 mg/Day     Additional OAD  
Number of Participants Analyzed  
[units: participants]
  239     120  
Change in HbA1c From Baseline to Week 52  
[units: percentage of glycosylated haemoglobin]
Mean ± Standard Error
  -1.21  ± 0.05     -0.94  ± 0.07  


Statistical Analysis 1 for Change in HbA1c From Baseline to Week 52
Groups [1] All groups
Method [2] ANOVA
P Value [3] 0.0026
Estimated treatment difference, Mean [4] -0.27
95% Confidence Interval ( -0.44 to -0.09 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Change in FPG From Baseline to Week 52   [ Time Frame: Week 0, week 52 ]

Measure Type Secondary
Measure Title Change in FPG From Baseline to Week 52
Measure Description Estimated mean change from baseline in FPG after 52 Weeks of treatment
Time Frame Week 0, week 52  
Safety Issue No  

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.
Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products and missing data were imputed using last observation carried forward (LOCF). One subject did not contribute to the statistical analysis at Week 52.

Reporting Groups
  Description
Liraglutide 0.9 mg/Day Liraglutide 0.9 mg/day was injected subcutaneously, once daily in morning or evening in addition to unchanged pre-trial oral anti-diabetic drug (OAD) (either glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) for 52 weeks. Liraglutide was started at 0.3 mg/day and dose was escalated to maximum dose level of 0.9 mg/day by weekly increment of 0.3 mg.
Additional OAD Subject's received additional OAD to pre-trial OAD. The type and dosage of additional OAD was chosen based on each individual’s glycaemic control by the investigator as per Japanese labelling.

Measured Values
    Liraglutide 0.9 mg/Day     Additional OAD  
Number of Participants Analyzed  
[units: participants]
  239     120  
Change in FPG From Baseline to Week 52  
[units: mmol/L]
Mean ± Standard Error
  -1.55  ± 0.09     -1.24  ± 0.12  


Statistical Analysis 1 for Change in FPG From Baseline to Week 52
Groups [1] All groups
Method [2] ANOVA
P Value [3] 0.0458
Estimated treatment difference, Mean [4] -0.30
95% Confidence Interval ( -0.60 to -0.01 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.




  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
No text entered.


  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: NCT01512108     History of Changes
Other Study ID Numbers: NN2211-3924, U1111-1121-3457, JapicCTI-121744
Study First Received: January 10, 2012
Results First Received: April 25, 2014
Last Updated: April 25, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare