Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

To Evaluate the Effect of Liraglutide Versus Glimepiride (Amaryl®) on Haemoglobin A1c (LEAD-3)

This study has been terminated.
(The trial was terminated at week 195 due to an insufficient number of subjects remaining to obtain reasonable statistical power)
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00294723
First received: February 20, 2006
Last updated: June 25, 2014
Last verified: June 2014
Results First Received: February 23, 2010  
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: glimepiride
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
A total of 138 centres in two countries: United States of America (USA) (126) and Mexico (12).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects with type 2 diabetes treated with diet/exercise or OAD (Oral Anti-Diabetic Drug) monotherapy for at least 2 months were eligible. One subject randomised to the liraglutide 1.8 mg group was withdrawn from the study prior to dosing due to protocol non compliance, subject was not included in the intent-to-treat (ITT) or safety analysis sets.

Reporting Groups
  Description
Lira 1.8 Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)
Lira 1.2 Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)
Glimepiride Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)

Participant Flow for 3 periods

Period 1:   Double-Blind Period 52 Weeks
    Lira 1.8     Lira 1.2     Glimepiride  
STARTED     247 [1]   251 [1]   248 [1]
Exposed to Study Drug     246 [2]   251     248  
COMPLETED     173     162     152  
NOT COMPLETED     74     89     96  
Adverse Event                 18                 25                 15  
Lack of Efficacy                 9                 15                 25  
Protocol Violation                 11                 11                 5  
Not specified in study report                 36                 38                 51  
[1] Randomised
[2] Subject withdrew before exposure to drug, and thus not included in the safety and ITT analysis sets

Period 2:   Open-Label Extension 52 Weeks
    Lira 1.8     Lira 1.2     Glimepiride  
STARTED     154 [1]   149 [2]   137 [3]
COMPLETED     114     110     97  
NOT COMPLETED     40     39     40  
Adverse Event                 5                 5                 2  
Lack of Efficacy                 12                 15                 21  
Protocol Violation                 4                 3                 3  
Not specified in study report                 19                 16                 14  
[1] 19 subjects did not continue into the extension period
[2] 13 subjects did not continue into the extension period
[3] 15 subjects did not continue into the extension period

Period 3:   Additional Open-Label Extension 91 Weeks
    Lira 1.8     Lira 1.2     Glimepiride  
STARTED     62 [1]   53 [2]   28 [3]
COMPLETED     34     32     8  
NOT COMPLETED     28     21     20  
Adverse Event                 1                 1                 0  
Lack of Efficacy                 24                 14                 16  
Protocol Violation                 1                 1                 1  
Not specified in study report                 2                 5                 3  
[1] 52 subjects did not continue into the extension period
[2] 57 subjects did not continue into the extension period
[3] 69 subjects did not continue into the extension period



  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
Lira 1.8 Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)
Lira 1.2 Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)
Glimepiride Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Total Total of all reporting groups

Baseline Measures
    Lira 1.8     Lira 1.2     Glimepiride     Total  
Number of Participants  
[units: participants]
  247     251     248     746  
Age  
[units: participants]
       
<=18 years     0     0     0     0  
Between 18 and 65 years     222     208     208     638  
>=65 years     25     43     40     108  
Age  
[units: years]
Mean ± Standard Deviation
  52.0  ± 10.8     53.7  ± 11.0     53.4  ± 10.9     53.0  ± 10.9  
Gender  
[units: participants]
       
Female     126     134     115     375  
Male     121     117     133     371  
Ethnicity (NIH/OMB)  
[units: participants]
       
Hispanic or Latino     87     81     93     261  
Not Hispanic or Latino     160     170     155     485  
Unknown or Not Reported     0     0     0     0  
Race (NIH/OMB)  
[units: participants]
       
American Indian or Alaska Native     0     0     0     0  
Asian     12     5     9     26  
Native Hawaiian or Other Pacific Islander     2     0     0     2  
Black or African American     30     34     30     94  
White     186     200     192     578  
More than one race     0     0     0     0  
Unknown or Not Reported     17     12     17     46  
Region of Enrollment  
[units: participants]
       
Mexico     52     53     66     171  
United States     195     198     182     575  
Previous anti-diabetic treatment  
[units: participants]
       
Diet/Exercise     87     91     94     272  
Monotherapy     160     160     154     474  
Body Mass Index (BMI)  
[units: kg/m^2]
Mean ± Standard Deviation
  32.8  ± 6.3     33.2  ± 5.6     33.2  ± 5.6     33.1  ± 5.8  
Duration of diabetes [1]
[units: years]
Mean ± Standard Deviation
  5.3  ± 5.1     5.2  ± 5.5     5.6  ± 5.1     5.4  ± 5.3  
HbA1c (Glycosylated Haemoglobin A1c) [2]
[units: percentage of total haemoglobin]
Mean ± Standard Deviation
  8.3  ± 1.1     8.3  ± 1.0     8.4  ± 1.2     8.3  ± 1.1  
[1] Number of years since diagnosis
[2] HbA1c at screening



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52   [ Time Frame: week 0, week 52 ]

2.  Primary:   Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104   [ Time Frame: week 0, week 104 ]

3.  Primary:   Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156   [ Time Frame: week 0, week 156 ]

4.  Secondary:   Change in Body Weight at Week 52   [ Time Frame: week 0, week 52 ]

5.  Secondary:   Change in Body Weight at Week 104   [ Time Frame: week 0, week 104 ]

6.  Secondary:   Change in Body Weight at Week 156   [ Time Frame: week 0, week 156 ]

7.  Secondary:   Change in Fasting Plasma Glucose at Week 52   [ Time Frame: week 0, week 52 ]

8.  Secondary:   Change in Fasting Plasma Glucose at Week 104   [ Time Frame: week 0, week 104 ]

9.  Secondary:   Change in Fasting Plasma Glucose at Week 156   [ Time Frame: week 0, week 156 ]

10.  Secondary:   Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52   [ Time Frame: week 0, week 52 ]

11.  Secondary:   Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104   [ Time Frame: week 0, week 104 ]

12.  Secondary:   Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156   [ Time Frame: week 0, week 156 ]

13.  Secondary:   Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52   [ Time Frame: week 0, week 52 ]

14.  Secondary:   Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104   [ Time Frame: week 0, week 104 ]

15.  Secondary:   Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156   [ Time Frame: week 0, week 156 ]

16.  Secondary:   Hypoglycaemic Episodes   [ Time Frame: weeks 0-104 ]

17.  Secondary:   Hypoglycaemic Episodes   [ Time Frame: weeks 104-195 ]


  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
Trial terminated due to an insufficient number of subjects remaining to obtain reasonable statistical power. Efficacy data was not analysed after week 156. Safety data was collected through week 195. No data was available from week 195 to 260


  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 by Novo Nordisk A/S

Publications automatically indexed to this study:

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00294723     History of Changes
Obsolete Identifiers: NCT00853359
Other Study ID Numbers: NN2211-1573
Study First Received: February 20, 2006
Results First Received: February 23, 2010
Last Updated: June 25, 2014
Health Authority: Mexico: Federal Commission for Protection Against Health Risks
United States: Food and Drug Administration