Clinical Trial Results:
A phase 4, monocenter, randomized, open label, comparator-controlled, parallel-group, mechanistic intervention trial to assess the effect of 8-week treatment with the glucagon-like peptide-1 receptor agonist lixisenatide versus insulin glulisine on renal physiology and biomarkers in insulin glargine-treated patients with type 2 diabetes mellitus

Trial information Top of page
Trial identification
Sponsor protocol code	DC2014ELIX001
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	U1111-1151-0579
Sponsors
Sponsor organisation name	VU University Medical Center
Sponsor organisation address	De Boelelaan 1117, Amsterdam, Netherlands,
Public contact	Lennart Tonneijck, VU University Medical Center, 0031 0204440651, l.tonneijck@vumc.nl
Scientific contact	Lennart Tonneijck, VU University Medical Center, 0031 0204440651, l.tonneijck@vumc.nl
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	21 Oct 2019
Is this the analysis of the primary completion data?	Yes
Primary completion date	14 Aug 2019
Global end of trial reached?	Yes
Global end of trial date	14 Aug 2019
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	Primary objective: To assess the long-term effects (i.e. after 8-week drug exposure) of the GLP-1RA lixisenatide versus insulin glulisine on renal hemodynamics (glomerular filtration rate/effective renal plasma flow) in patients with type 2 diabetes
Protection of trial subjects	n.a.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	01 Sep 2014
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Netherlands: 40
Worldwide total number of subjects	40
EEA total number of subjects	40
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	26
From 65 to 84 years	14
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	-
Pre-assignment
Screening details	51 patients were screened, 40 were included
Period 1
Period 1 title	trial (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator
Arms
Are arms mutually exclusive	Yes
Arm title	Lixisenatide
Arm description	-
Arm type	Experimental
Investigational medicinal product name	lixisenatide
Investigational medicinal product code
Other name
Pharmaceutical forms	Solution for injection in pre-filled pen
Routes of administration	Subcutaneous use
Dosage and administration details	once daily 20 mcg
Arm title	Glulisine
Arm description	-
Arm type	Active comparator
Investigational medicinal product name	insulin glulisine
Investigational medicinal product code
Other name
Pharmaceutical forms	Solution for injection in pre-filled pen
Routes of administration	Subcutaneous use
Dosage and administration details	once daily at breakfast, starting at 2 units - titration towards glucose 5-8 2-hr after breakfast
Number of subjects in period 1 [1] Lixisenatide Glulisine Started 20 19 Completed 17 18 Not completed 3 1      Adverse event, non-fatal 3 -      Protocol deviation - 1
Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: One patient was included in the study, yet withdrew consent before randomisation

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Lixisenatide
Reporting group description	-
Reporting group title	Glulisine
Reporting group description	-
Reporting group values Lixisenatide Glulisine Total Number of subjects 20 19 39 Age categorical Units: Subjects     In utero 0     Preterm newborn infants (gestational age < 37 wks) 0     Newborns (0-27 days) 0     Infants and toddlers (28 days-23 months) 0     Children (2-11 years) 0     Adolescents (12-17 years) 0     Adults (18-64 years) 0     From 65-84 years 0     85 years and over 0 Age continuous Units: years     geometric mean (standard deviation) 62 ( 7 ) 61 ( 7 ) - Gender categorical Units: Subjects     Female 8 8 16     Male 12 11 23

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Lixisenatide
Reporting group description	-
Reporting group title	Glulisine
Reporting group description	-
Subject analysis set title	Kidney function
Subject analysis set type	Per protocol
Subject analysis set description	Kidney function

End points Top of page

Primary: Kidney function Top of page
End point title	Kidney function
End point description
End point type	Primary
End point timeframe	full study
End point values Lixisenatide Glulisine Kidney function Number of subjects analysed 17 18 35 Units: 1     geometric mean (standard error) 92 ( 4 ) 83 ( 5 ) 0.1 ( 0.1 )
Statistical analysis title	GFR
Comparison groups	Lixisenatide v Glulisine
Number of subjects included in analysis	35
Analysis specification	Pre-specified
Analysis type	equivalence
P-value	= 0.989
Method	Regression, Linear
Confidence interval

Primary: Kidney function Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	entire study
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	no dictionary used
Dictionary version	0
Reporting groups
Reporting group title	Glulisin
Reporting group description	-
Reporting group title	Lixisenatide
Reporting group description	-
Serious adverse events Glulisin Lixisenatide Total subjects affected by serious adverse events      subjects affected / exposed 1 / 19 (5.26%) 0 / 20 (0.00%)      number of deaths (all causes) 0 0      number of deaths resulting from adverse events 0 0 Cardiac disorders Atrial fibrillation Additional description: one patient randomised to insulin glulisin experienced two episodes of (new-onset) symptomatic atrial fibrillation after the astart of the intervention. Patient recovered fully after hospital admision      subjects affected / exposed 1 / 19 (5.26%) 0 / 20 (0.00%)      occurrences causally related to treatment / all 0 / 2 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 0%
Non-serious adverse events Glulisin Lixisenatide Total subjects affected by non serious adverse events      subjects affected / exposed 13 / 19 (68.42%) 11 / 20 (55.00%) Gastrointestinal disorders Nausea      subjects affected / exposed 0 / 19 (0.00%) 11 / 20 (55.00%)      occurrences all number 0 11 Endocrine disorders Hypoglycaemia      subjects affected / exposed 13 / 19 (68.42%) 0 / 20 (0.00%)      occurrences all number 0 0

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported
Online references
http://www.ncbi.nlm.nih.gov/pubmed/30353743 http://www.ncbi.nlm.nih.gov/pubmed/29915021 http://www.ncbi.nlm.nih.gov/pubmed/29341461 http://www.ncbi.nlm.nih.gov/pubmed/28449402

More information Top of page