Clinical Trial Results:
A Phase IIa, 28day treatment, multicentre, randomised, comparatorcontrolled, observerblind trial with intraindividual left/right comparison to investigate the antipsoriatic efficacy and the safety of an LAS41004 formulation in comparison to an active reference in patients with mild to moderate plaque psoriasis
Summary


EudraCT number 
201300375722 
Trial protocol 
DE 
Global end of trial date 
13 Oct 2014

Results information


Results version number 
v1(current) 
This version publication date 
25 Jun 2016

First version publication date 
25 Jun 2016

Other versions 
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
H5530001309


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT02180464  
WHO universal trial number (UTN) 
  
Sponsors


Sponsor organisation name 
Almirall Hermal GmbH


Sponsor organisation address 
Scholtzstraße 3, Reinbek, Germany, 21465


Public contact 
Disclosure Central Team, ALMIRALL S.A., R&D@almirall.com


Scientific contact 
Disclosure Central Team, ALMIRALL S.A., R&D@almirall.com


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 
13 Oct 2014


Is this the analysis of the primary completion data? 
Yes


Primary completion date 
13 Oct 2014


Global end of trial reached? 
Yes


Global end of trial date 
13 Oct 2014


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
To assess the antipsoriatic efficacy and safety of the combination of LAS41004 (bexarotene plus betamethasone dipropionate) in a topical formulation by reference to Daivobet® ointment (calcipotriol plus betamethasone dipropionate)


Protection of trial subjects 
The study was conducted in accordance with legal and regulatory requirements, as well as the general principles set forth in the International Conference on Harmonisation (ICH) Guidelines for Good Clinical Practice (GCP) and applicable local regulatory requirements and laws. As such, screening assessments were performed after the patient had agreed to participate and had signed and dated the informed consent form, and safety and tolerability were evaluated throughout the study by monitoring of adverse events, performing laboratory tests and physical examinations, and measuring vital signs


Background therapy 
  
Evidence for comparator 
  
Actual start date of recruitment 
13 Jun 2014


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
Yes


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
Germany: 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 (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
36


From 65 to 84 years 
4


85 years and over 
0



Recruitment


Recruitment details 
  
Preassignment


Screening details 
30 ± 3 days prior to the first IMP administration (women) and up to 30 days prior to the first IMP administration (men), subjects underwent initial screening. Of 43 subjects screened, 3 subjects were not enrolled due to screen failure  
Period 1


Period 1 title 
Overall study (overall period)


Is this the baseline period? 
Yes  
Allocation method 
Randomised  controlled


Blinding used 
Single blind  
Roles blinded 
Subject  
Arms


Are arms mutually exclusive 
No


Arm title

LAS41004  
Arm description 
Oncedaily topical application of LAS41004 (bexarotene 1% plus betamethasone dipropionate 0.064%) approximately 2–6 mg/cm2 to an area of 20–300 cm2  
Arm type 
Experimental  
Investigational medicinal product name 
LAS41004


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Gel


Routes of administration 
Topical use , Cutaneous use


Dosage and administration details 
Approximately 2 – 6 mg/cm2 of test product was applied by the patient to lesional areas (20–300 cm2) each, once daily without occlusion on 28 consecutive days. Each test product was applied once daily for a total of 28 days


Arm title

Daivobet  
Arm description 
Oncedaily topical application of Daivobet (calcipotriol 0.05 mg/g plus betamethasone dipropionate 0.5 mg/g [BDP 0.643 mg/g]) approximately 2–6 mg/cm2 to an area of 20–300 cm2  
Arm type 
Active comparator  
Investigational medicinal product name 
Daivobet


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Ointment


Routes of administration 
Cutaneous use, Topical use


Dosage and administration details 
Approximately 2–6 mg/cm2 of test product was applied by the patient to lesional areas (20–300 cm2) each, once daily without occlusion on 28 consecutive days. Each test product was applied once daily for a total of 28 days





Baseline characteristics reporting groups


Reporting group title 
Overall study


Reporting group description 
  



End points reporting groups


Reporting group title 
LAS41004


Reporting group description 
Oncedaily topical application of LAS41004 (bexarotene 1% plus betamethasone dipropionate 0.064%) approximately 2–6 mg/cm2 to an area of 20–300 cm2  
Reporting group title 
Daivobet


Reporting group description 
Oncedaily topical application of Daivobet (calcipotriol 0.05 mg/g plus betamethasone dipropionate 0.5 mg/g [BDP 0.643 mg/g]) approximately 2–6 mg/cm2 to an area of 20–300 cm2 


End point title 
Change from baseline in total sign score on Day 29  
End point description 
Total sign score (TSS) was defined as the sum of individual scores for erythema, scaling and infiltration using a 5point scale (0 = absent, 1 = slight, 2 = moderate, 3 = severe, 4 = severest possible)


End point type 
Primary


End point timeframe 
Day 29




Statistical analysis title 
Day 29 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0001  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
1.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.3



End point title 
Change from baseline in total sign score  
End point description 
Total sign score (TSS) was defined as the sum of individual scores for erythema, scaling and infiltration using a 5point scale (0 = absent, 1 = slight, 2 = moderate, 3 = severe, 4 = severest possible)


End point type 
Secondary


End point timeframe 
Up to day 29




Statistical analysis title 
Day 4 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[1]}  
Pvalue 
= 0.0066  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
1.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.23


Notes [1]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 8 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[2]}  
Pvalue 
= 0.001  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
1.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.3


Notes [2]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 15 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[3]}  
Pvalue 
< 0  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
1.9  
Variability estimate 
Standard error of the mean


Dispersion value 
0.28


Notes [3]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 22 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[4]}  
Pvalue 
< 0  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
2.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.29


Notes [4]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 29 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[5]}  
Pvalue 
< 0.0001  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
1.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.3


Notes [5]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 


End point title 
Change from baseline in erythema  
End point description 
Individual scores for erythema, scaling and infiltration were assessed using a 5point scale (0 = absent, 1 = slight, 2 = moderate, 3 = severe, 4 = severest possible)


End point type 
Secondary


End point timeframe 
Up to Day 29




Statistical analysis title 
Day 4 LAS41004 v Daivobet  
Comparison groups 
Daivobet v LAS41004


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[6]}  
Pvalue 
= 0.3981  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.09


Notes [6]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 8 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[7]}  
Pvalue 
= 0.2461  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Notes [7]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 15 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[8]}  
Pvalue 
= 0.0647  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Notes [8]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 22 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[9]}  
Pvalue 
= 0.0159  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [9]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 29 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[10]}  
Pvalue 
= 0.0152  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Notes [10]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 


End point title 
Change from baseline in scaling  
End point description 
Individual scores for erythema, scaling and infiltration were assessed using a 5point scale (0 = absent, 1 = slight, 2 = moderate, 3 = severe, 4 = severest possible)


End point type 
Secondary


End point timeframe 
Up to Day 29




Statistical analysis title 
Day 4 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[11]}  
Pvalue 
= 0.0541  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [11]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 8 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[12]}  
Pvalue 
= 0.0003  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.9  
Variability estimate 
Standard error of the mean


Dispersion value 
0.15


Notes [12]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 15 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[13]}  
Pvalue 
= 0.0002  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.13


Notes [13]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 22 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[14]}  
Pvalue 
< 0  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.9  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Notes [14]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 29 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[15]}  
Pvalue 
= 0.0015  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [15]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 


End point title 
Change from baseline in infiltration  
End point description 
Individual scores for erythema, scaling and infiltration were assessed using a 5point scale (0 = absent, 1 = slight, 2 = moderate, 3 = severe, 4 = severest possible)


End point type 
Secondary


End point timeframe 
Up to Day 29




Statistical analysis title 
Day 4 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[16]}  
Pvalue 
= 0.0021  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Notes [16]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 8 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[17]}  
Pvalue 
= 0.0243  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Notes [17]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 15 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[18]}  
Pvalue 
< 0  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.13


Notes [18]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 22 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[19]}  
Pvalue 
< 0  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [19]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 29 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[20]}  
Pvalue 
= 0.0001  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.13


Notes [20]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 


End point title 
Change from baseline in Physician's Global Assessment  
End point description 
The overall clinical picture of psoriasis of the respective lesion was scored from severe to clear using a 6point scale (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = moderate to severe, 5 = severe)


End point type 
Secondary


End point timeframe 
Up to Day 29




Statistical analysis title 
Day 4 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[21]}  
Pvalue 
= 0.1192  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Notes [21]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 8 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[22]}  
Pvalue 
= 0.0133  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [22]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 15 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[23]}  
Pvalue 
= 0.0028  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Notes [23]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 22 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[24]}  
Pvalue 
< 0.0001  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.9  
Variability estimate 
Standard error of the mean


Dispersion value 
0.15


Notes [24]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 

Statistical analysis title 
Day 29 LAS41004 v Daivobet  
Comparison groups 
LAS41004 v Daivobet


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority ^{[25]}  
Pvalue 
= 0.0008  
Method 
ANCOVA  
Parameter type 
LS mean difference  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Notes [25]  The number of participants in this analysis is automatically calculated by the database. The arms are not mutually exclusive and the number of patients in this analysis is 40, not 80 


Adverse events information


Timeframe for reporting adverse events 
Up to 7 days after last study drug administration


Assessment type 
Systematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
17.0


Reporting groups


Reporting group title 
LAS41004


Reporting group description 
LAS41004 (bexarotene 1% plus betamethasone dipropionate 0.064% ) oncedaily topical application of approximately 26 mg/cm2 to an area of 20300 cm2  
Reporting group title 
Daivobet


Reporting group description 
Once daily topical application of Daivobet (calcipotriol 0.05 mg/g plus betamethasone dipropionate 0.5 mg/g [BDP 0.643 mg/g]) approximately 26 mg/cm2 to an area of 20300 cm2  


Frequency threshold for reporting nonserious adverse events: 2%  



Substantial protocol amendments (globally) 

Were there any global substantial amendments to the protocol? Yes  
Date 
Amendment 

15 Apr 2014 
Amendment 1 was necessary due to conditions and advice noted by the BfArM (Bundesinstitut fuer Arzneimittel und Medizinprodukte [German Federal Institute for Drugs and Medical Devices]) regarding stress and risks, inclusion and exclusion criteria, restrictions, manner of treatment, pregnancy test and measurement/assessment time points 

24 Apr 2014 
Amendment 2 was necessary due to new information regarding the analysis of stability for the LAS41004 formulation and a consequent correction of the corresponding storage conditions 

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 