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Trial record 25 of 61 for:    Lixisenatide

Efficacy and Safety of Liraglutide Versus Lixisenatide as add-on to Metformin in Subjects With Type 2 Diabetes (LIRA-LIXI™)

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ClinicalTrials.gov Identifier: NCT01973231
Recruitment Status : Completed
First Posted : October 31, 2013
Results First Posted : December 22, 2015
Last Update Posted : February 9, 2017
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Diabetes
Diabetes Mellitus, Type 2
Interventions Drug: liraglutide
Drug: lixisenatide
Enrollment 404
Recruitment Details The trial was conducted at 56 sites in 9 countries; Czech Republic (5), Finland (4), France (6), Germany (8), Hungary (6), Italy (5), Latvia (6), Lithuania (5) and UK (11).
Pre-assignment Details  
Arm/Group Title Liraglutide Lixisenatide
Hide Arm/Group Description Liraglutide was administered subcutaneously (s.c.; under the skin) once daily in addition to the subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000 mg/day and up to 3000 mg/day) for a total duration of 26 weeks. Starting dose of liraglutide was 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day was reached. Lixisenatide was administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000mg/day and up to 3000mg/day) for a total duration of 26 weeks. Starting dose of lixisenatide was 10 µg once daily, the dose was escalated to 20 µg once daily from day 15 after randomisation.
Period Title: Overall Study
Started 202 202
Completed 191 190
Not Completed 11 12
Reason Not Completed
Protocol Violation             1             1
Lost to Follow-up             1             1
unclassified             2             1
Withdrawal by Subject             7             9
Arm/Group Title Liraglutide Lixisenatide Total
Hide Arm/Group Description Liraglutide was administered subcutaneously (s.c.; under the skin) once daily in addition to the subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000 mg/day and up to 3000 mg/day) for a total duration of 26 weeks. Starting dose of liraglutide was 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day was reached. Lixisenatide was administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000mg/day and up to 3000mg/day) for a total duration of 26 weeks. Starting dose of lixisenatide was 10 µg once daily, the dose was escalated to 20 µg once daily from day 15 after randomisation. Total of all reporting groups
Overall Number of Baseline Participants 202 202 404
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 202 participants 202 participants 404 participants
56.3  (10.6) 56.1  (10.0) 56.2  (10.3)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 202 participants 202 participants 404 participants
Female
70
  34.7%
90
  44.6%
160
  39.6%
Male
132
  65.3%
112
  55.4%
244
  60.4%
Glycosylated Haemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percent (%) glycosylated haemoglobin
Number Analyzed 202 participants 202 participants 404 participants
8.40  (0.723) 8.43  (0.785) 8.41  (0.754)
Fasting plasma glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 202 participants 202 participants 404 participants
10.47  (2.368) 10.25  (2.254) 10.36  (2.312)
Body Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 202 participants 202 participants 404 participants
101.89  (23.344) 100.58  (19.949) 101.24  (21.696)
1.Primary Outcome
Title Change in Glycosylated Haemoglobin (HbA1c) From Baseline
Hide Description Change from baseline in HbA1c after 26 weeks of treatment.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomised subjects. Missing values were imputed using predicted values from the mixed model for repeated measurements (MMRM) model. Due to missing HbA1c post baseline data, 194 and 191 subjects in liraglutide and lixisenatide treatment group, respectively were included in the HbA1c analysis.
Arm/Group Title Liraglutide Lixisenatide
Hide Arm/Group Description:
Liraglutide was administered subcutaneously (s.c.; under the skin) once daily in addition to the subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000 mg/day and up to 3000 mg/day) for a total duration of 26 weeks. Starting dose of liraglutide was 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day was reached.
Lixisenatide was administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000mg/day and up to 3000mg/day) for a total duration of 26 weeks. Starting dose of lixisenatide was 10 µg once daily, the dose was escalated to 20 µg once daily from day 15 after randomisation.
Overall Number of Participants Analyzed 194 191
Mean (Standard Deviation)
Unit of Measure: Percent (%) glycosylated haemoglobin
-1.809  (0.9159) -1.238  (1.0085)
2.Secondary Outcome
Title Change in Fasting Plasma Glucose (FPG) From Baseline
Hide Description Change from baseline in FPG after 26 weeks of treatment.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects. Missing values were imputed using predicted values from the MMRM model. Due to missing FPG post baseline data, 194 and 189 subjects in liraglutide and lixisenatide treatment group, respectively were included in the FPG analysis.
Arm/Group Title Liraglutide Lixisenatide
Hide Arm/Group Description:
Liraglutide was administered subcutaneously (s.c.; under the skin) once daily in addition to the subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000 mg/day and up to 3000 mg/day) for a total duration of 26 weeks. Starting dose of liraglutide was 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day was reached.
Lixisenatide was administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000mg/day and up to 3000mg/day) for a total duration of 26 weeks. Starting dose of lixisenatide was 10 µg once daily, the dose was escalated to 20 µg once daily from day 15 after randomisation.
Overall Number of Participants Analyzed 194 189
Mean (Standard Deviation)
Unit of Measure: mmol/L
-2.904  (2.2309) -1.644  (2.1511)
3.Secondary Outcome
Title Change in Body Weight From Baseline
Hide Description Change from baseline in body weight after 26 weeks of treatment.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects. Missing values were imputed using predicted values from the MMRM model. Due to missing body weight post baseline data, 194 and 191 subjects in liraglutide and lixisenatide treatment group, respectively were included in the body weight analysis.
Arm/Group Title Liraglutide Lixisenatide
Hide Arm/Group Description:
Liraglutide was administered subcutaneously (s.c.; under the skin) once daily in addition to the subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000 mg/day and up to 3000 mg/day) for a total duration of 26 weeks. Starting dose of liraglutide was 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day was reached.
Lixisenatide was administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000mg/day and up to 3000mg/day) for a total duration of 26 weeks. Starting dose of lixisenatide was 10 µg once daily, the dose was escalated to 20 µg once daily from day 15 after randomisation.
Overall Number of Participants Analyzed 194 191
Mean (Standard Deviation)
Unit of Measure: kg
-4.24  (4.273) -3.69  (4.746)
4.Secondary Outcome
Title Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) (American Diabetes Association (ADA) Target) (Yes/no)
Hide Description Subjects who achieved HbA1c below 7.0% (53 mmol/mol) after 26 weeks of treatment (yes/no).
Time Frame After 26 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects. Missing values were imputed using predicted values from the MMRM model. Due to missing HbA1c post baseline data, 194 and 191 subjects in liraglutide and lixisenatide treatment group, respectively were included in the HbA1c analysis.
Arm/Group Title Liraglutide Lixisenatide
Hide Arm/Group Description:
Liraglutide was administered subcutaneously (s.c.; under the skin) once daily in addition to the subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000 mg/day and up to 3000 mg/day) for a total duration of 26 weeks. Starting dose of liraglutide was 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day was reached.
Lixisenatide was administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000mg/day and up to 3000mg/day) for a total duration of 26 weeks. Starting dose of lixisenatide was 10 µg once daily, the dose was escalated to 20 µg once daily from day 15 after randomisation.
Overall Number of Participants Analyzed 194 191
Measure Type: Number
Unit of Measure: percentage (%) of subjects
Yes 74.2 45.5
No 25.8 54.5
5.Secondary Outcome
Title Subjects Who Achieve HbA1c Equal to or Below 6.5% (48 mmol/Mol) (American Association of Clinical Endocrinologists [AACE] Target) (Yes/no)
Hide Description Subjects who achieved HbA1c below equal to or below 6.5% (48 mmol/mol) after 26 weeks of treatment (yes/no).
Time Frame After 26 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects. Missing values were imputed using predicted values from the MMRM model. Due to missing HbA1c post baseline data, 194 and 191 subjects in liraglutide and lixisenatide treatment group, respectively were included in the HbA1c analysis.
Arm/Group Title Liraglutide Lixisenatide
Hide Arm/Group Description:
Liraglutide was administered subcutaneously (s.c.; under the skin) once daily in addition to the subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000 mg/day and up to 3000 mg/day) for a total duration of 26 weeks. Starting dose of liraglutide was 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day was reached.
Lixisenatide was administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000mg/day and up to 3000mg/day) for a total duration of 26 weeks. Starting dose of lixisenatide was 10 µg once daily, the dose was escalated to 20 µg once daily from day 15 after randomisation.
Overall Number of Participants Analyzed 194 191
Measure Type: Number
Unit of Measure: percentage (%) of subjects
Yes 54.6 26.2
No 45.4 73.8
6.Secondary Outcome
Title Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain (Yes/no)
Hide Description Subjects who achieved HbA1c below 7.0% (53 mmol/mol) and no weight gain after 26 weeks of treatment (yes/no).
Time Frame After 26 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects. Missing values were imputed using predicted values from the MMRM model. Due to missing HbA1c post-baseline data, 194 and 191 subjects in liraglutide and lixisenatide treatment group, respectively were included in the HbA1c analysis.
Arm/Group Title Liraglutide Lixisenatide
Hide Arm/Group Description:
Liraglutide was administered subcutaneously (s.c.; under the skin) once daily in addition to the subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000 mg/day and up to 3000 mg/day) for a total duration of 26 weeks. Starting dose of liraglutide was 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day was reached.
Lixisenatide was administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000mg/day and up to 3000mg/day) for a total duration of 26 weeks. Starting dose of lixisenatide was 10 µg once daily, the dose was escalated to 20 µg once daily from day 15 after randomisation.
Overall Number of Participants Analyzed 194 191
Measure Type: Number
Unit of Measure: percentage (%) of subjects
Yes 66.5 41.9
No 33.5 58.1
7.Secondary Outcome
Title Number of Treatment Emergent Adverse Events (TEAEs)
Hide Description A Treatment Emergent Adverse Event (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. Severity was assessed by investigator.
Time Frame Weeks 0-26
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAS) included all subjects who received at least one dose of any of the trial products.
Arm/Group Title Liraglutide Lixisenatide
Hide Arm/Group Description:
Liraglutide was administered subcutaneously (s.c.; under the skin) once daily in addition to the subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000 mg/day and up to 3000 mg/day) for a total duration of 26 weeks. Starting dose of liraglutide was 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day was reached.
Lixisenatide was administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000mg/day and up to 3000mg/day) for a total duration of 26 weeks. Starting dose of lixisenatide was 10 µg once daily, the dose was escalated to 20 µg once daily from day 15 after randomisation.
Overall Number of Participants Analyzed 202 202
Measure Type: Number
Unit of Measure: events
Events 540 435
Serious 13 7
Severe 10 3
Moderate 109 84
Mild 421 348
Time Frame Weeks 0-26
Adverse Event Reporting Description The SAS included all subjects who received at least one dose of any of the trial products.
 
Arm/Group Title Liraglutide Lixisenatide
Hide Arm/Group Description Liraglutide was administered subcutaneously (s.c.; under the skin) once daily in addition to the subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000 mg/day and up to 3000 mg/day) for a total duration of 26 weeks. Starting dose of liraglutide was 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day was reached. Lixisenatide was administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (maximum tolerated dose, equal to or above 1000mg/day and up to 3000mg/day) for a total duration of 26 weeks. Starting dose of lixisenatide was 10 µg once daily, the dose was escalated to 20 µg once daily from day 15 after randomisation.
All-Cause Mortality
Liraglutide Lixisenatide
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Liraglutide Lixisenatide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/202 (5.94%)      7/202 (3.47%)    
Cardiac disorders     
Atrial fibrillation  1  0/202 (0.00%)  0 1/202 (0.50%)  1
Cardiac failure  1  0/202 (0.00%)  0 1/202 (0.50%)  1
Coronary artery disease  1  0/202 (0.00%)  0 1/202 (0.50%)  1
Myocardial ischaemia  1  1/202 (0.50%)  1 0/202 (0.00%)  0
Gastrointestinal disorders     
Abdominal hernia  1  1/202 (0.50%)  1 0/202 (0.00%)  0
Gastric ulcer haemorrhage  1  1/202 (0.50%)  1 0/202 (0.00%)  0
Oesophageal ulcer haemorrhage  1  1/202 (0.50%)  1 0/202 (0.00%)  0
General disorders     
Pyrexia  1  1/202 (0.50%)  1 0/202 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis acute  1  1/202 (0.50%)  1 0/202 (0.00%)  0
Infections and infestations     
Diabetic foot infection  1  1/202 (0.50%)  1 0/202 (0.00%)  0
Influenza  1  1/202 (0.50%)  1 0/202 (0.00%)  0
Lobar pneumonia  1  0/202 (0.00%)  0 1/202 (0.50%)  1
Injury, poisoning and procedural complications     
Thermal burn  1  0/202 (0.00%)  0 1/202 (0.50%)  1
Musculoskeletal and connective tissue disorders     
Rotator cuff syndrome  1  1/202 (0.50%)  1 0/202 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia  1  1/202 (0.50%)  1 0/202 (0.00%)  0
Nervous system disorders     
Ischaemic stroke  1  1/202 (0.50%)  1 0/202 (0.00%)  0
Syncope  1  1/202 (0.50%)  1 0/202 (0.00%)  0
Psychiatric disorders     
Anxiety disorder  1 [1]  0/202 (0.00%)  0 1/202 (0.50%)  1
Reproductive system and breast disorders     
Prostatic dysplasia  1  0/202 (0.00%)  0 1/202 (0.50%)  1
Skin and subcutaneous tissue disorders     
Skin ulcer  1  1/202 (0.50%)  1 0/202 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
[1]
Complete preferred term of the AE: Anxiety disorder due to a general medical condition
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Liraglutide Lixisenatide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   90/202 (44.55%)      83/202 (41.09%)    
Gastrointestinal disorders     
Diarrhoea  1  25/202 (12.38%)  39 20/202 (9.90%)  22
Dyspepsia  1  11/202 (5.45%)  11 6/202 (2.97%)  9
Nausea  1  44/202 (21.78%)  67 44/202 (21.78%)  60
Vomiting  1  14/202 (6.93%)  18 18/202 (8.91%)  22
Infections and infestations     
Nasopharyngitis  1  13/202 (6.44%)  13 20/202 (9.90%)  22
Investigations     
Lipase increased  1  17/202 (8.42%)  17 5/202 (2.48%)  5
Metabolism and nutrition disorders     
Decreased appetite  1  13/202 (6.44%)  13 5/202 (2.48%)  5
Nervous system disorders     
Headache  1  15/202 (7.43%)  31 17/202 (8.42%)  35
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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.
Novo Nordisk maintains the right to be informed of plans by any investigator to publish and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Any such communication must be submitted in writing to the Novo Nordisk trial manager before submission for comments. Comments will be given within four weeks from receipt of the planned communication.
Results Point of Contact
Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01973231     History of Changes
Other Study ID Numbers: NN2211-3867
2012-004984-27 ( EudraCT Number )
U1111-1136-3644 ( Other Identifier: WHO )
First Submitted: October 23, 2013
First Posted: October 31, 2013
Results First Submitted: November 18, 2015
Results First Posted: December 22, 2015
Last Update Posted: February 9, 2017