Clinical Trial Results:
Effects of once-daily administered GLP-1 Receptoragonist Lixisenatide in combination with basal Insulin on glycemic control in patients with type-2 diabetes mellitus not achieving therapeutic targets with premixed insulin strategy
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Summary
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EudraCT number |
2013-005334-37 |
Trial protocol |
AT |
Global end of trial date |
26 Jan 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Oct 2017
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First version publication date |
14 Oct 2017
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Other versions |
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Summary report(s) |
lixibit summary Switch to Combined GLP1 Receptor Agonist Lixisenatide with Basal Insulin Glargine in Poorly Controlled T2DM Patients with Premixed Insulin Therapy: A Clinical Observation and Pilot Study in Nine Patie |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
LixiBit
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02168491 | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Medical University Vienna
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Sponsor organisation address |
Spitalgasse 23, Vienna, Austria, 1090
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Public contact |
Medical University of Vienna, Medical University of Vienna, michael.krebs@meduniwien.ac.at
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Scientific contact |
Medical University of Vienna, Medical University of Vienna, michael.krebs@meduniwien.ac.at
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 Dec 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Jan 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Introduction of basal insulin therapy in combination with the GLP-1 receptor agonist Lixisenatide in patients with type-2 diabetes previously treated with premixed insulin not achieving therapeutic target will be associated with positive effects on glycemic control:
- Changes in HbA1c from baseline to end
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Protection of trial subjects |
serious adverse events and adverse events reported.
laboratory measurements and vital signs every visit
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Background therapy |
premixed insulin | ||
Evidence for comparator |
Premixed insulin-based therapy is a standard insulin treatment strategy in Austria. The widespread use of premixed insulin is explained by high acceptance by health care professionals and patients due to one single product and flexible number of injections (1-3 daily) which covers the demand in controlling fasting and postprandial glucose excursions of most patients with diabetes. However, the use of pre-mixed insulin frequently leads to a high insulin demand and consequently weight gain and an increased risk of hypoglycemia. Hence, achieve good metabolic control in these patients remains a major challenge. For those patients, the approach to treatment intensification without facing the typical risks of insulin treatment (hypoglycemia and weight increase) is of major importance. One, so far not exploited option may be the BIT-strategy: Basal insulin in combination with incretin-based therapy. Pathophysiologically basal insulin inhibits glucose production in the liver, decreases hepatic insulin resistance and improves the function of beta cells in the postprandial state by discharge of fasting insulin secretion. During further diabetes progression steadily increasing HbA1c levels - despite good fasting blood glucose control - indicate the need for additional intervention of meal-related glucose excursions. In this stage of type-2 diabetes basal insulin can be combined with prandial (short-acting) insulin or prandial GLP-1 receptor agonists. However, regarding important safety parameters: risks of hypoglycemia and weight gain in the long-term treatment GLP-1 receptor agonists are beneficial. Lixisenatide is a novel GLP-1 receptor agonist with a pronounced postprandial (PPG) effect which fits with basal insulin mode of action primarily focused on fasting blood glucose reduction. Therefore 10 patients (both gender) under treatment with premixed insulin (2-3 times daily) and HbA1c>7% will be switched to basal insulin glargine (Lantus, once daily) and GLP-1 re | ||
Actual start date of recruitment |
01 Jul 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 9
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Worldwide total number of subjects |
9
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EEA total number of subjects |
9
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
4
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
11 patients were screened Study Start Date: November 2014 Study Completion Date: August 2015 Primary Completion Date: July 2015 (Final data collection date for primary outcome measure) Austria, Vienna | ||||||||||
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Pre-assignment
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Screening details |
2 patients declined to participate because of time restraints, thus study medication was administered in 9 patients | ||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||
Blinding implementation details |
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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Arms
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Arm title
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Lixisenatide and Insulin Glargine | ||||||||||
Arm description |
10 type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Lixisenatide
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Investigational medicinal product code |
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Other name |
Lyxumia
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
once daily in the morning before breakfast; days 1-14 10 µg thereafter 20 µg
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Investigational medicinal product name |
Insulin Glargine
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Investigational medicinal product code |
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Other name |
Lantus
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
The (mean) daily dose of premixed insulin will be calculated based on the records of the run in period. The initial dose of insulin glargine will be adjusted at about 60% of the daily insulin dose of premixed insulin.
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
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End points reporting groups
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Reporting group title |
Lixisenatide and Insulin Glargine
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Reporting group description |
10 type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide | ||
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End point title |
Change in HbA1c From Baseline to End [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
12 Weeks from baseline to end
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: baseline to end analysis was not possible to enter, analysis performed with a paired t test. attachment with additional information includes those about statistical analysis |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
12 weeks, baseline to end
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10
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Reporting groups
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Reporting group title |
endocrine disorders
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Reporting group description |
mild asymptomatic hypoglycaemia # participants affected / at risk 3/9 (33.33%) # events 8 symptomatic hypoglycaemia # participants affected / at risk 1/9 (11.11%) # events 1 hypercholesterolaemia # participants affected / at risk 2/9 (22.22%) # events 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
eye disorders
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Reporting group description |
elective ambulatory cataract surgery | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
gastrointestinal disorders
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Reporting group description |
mild gastrointestinal complaints | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
general disorders
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Reporting group description |
cough | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
infections and infestations
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Reporting group description |
urinary tract infection | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
musculoskeletal and connective tissue disorders
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Reporting group description |
shoulder pain | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
renal and urinary disorders
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Reporting group description |
haematuria | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
surgical and medical procedures
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/28357772 |
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