Clinical Trial Results:
Safety and Efficacy of Calcipotriol plus Betamethasone Dipropionate Gel in Adolescent Patients (Aged 12 to 17 Years) with Scalp Psoriasis
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Summary
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EudraCT number |
2008-005456-24 |
Trial protocol |
FR GB |
Global end of trial date |
15 Oct 2012
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Feb 2016
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First version publication date |
22 Jul 2015
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Other versions |
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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 |
MBL 0412 INT
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
LEO Pharma A/S
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Sponsor organisation address |
Industriparken 55, Ballerup, Denmark,
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Public contact |
Clinical Trial Disclosure Manager, LEO Pharma A/S, +45 44945888, ctr.disclosure@leo-pharma.com
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Scientific contact |
Clinical Trial Disclosure Manager, LEO Pharma A/S, +45 44945888, ctr.disclosure@leo-pharma.com
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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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Oct 2012
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Oct 2012
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Oct 2012
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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 |
The primary objective is to evaluate the safety of once daily use of calcipotriol (50 mcg/g) plus betamethasone (0.5 mg/g) (as dipropionate) gel in adolescent subjects
(aged 12 to 17 years) with scalp psoriasis.
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Protection of trial subjects |
Not applicable
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
22 Nov 2010
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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 |
United Kingdom: 37
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Country: Number of subjects enrolled |
France: 22
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Country: Number of subjects enrolled |
Canada: 19
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Worldwide total number of subjects |
78
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EEA total number of subjects |
59
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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) |
78
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
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Pre-assignment
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Screening details |
Prior to Visit 1 (Day 0), a wash-out period (up to 8 weeks, as defined by the exclusion criteria) was to be completed if the subject had been treated with antipsoriatic treatments or other relevant medication; 2 screening visits were planned. | ||||||||||||||
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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 | ||||||||||||||
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Arms
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Arm title
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LEO 80185 Gel Once Daily Application | ||||||||||||||
Arm description |
Talconex® Scalp Topical Suspension/Daivobet® gel/Dovobet® gel/Xamiol® gel Calcipotriol 50 mcg/g plus betamethasone 0.5 mg/g (as dipropionate) gel once daily for up to 8 weeks to treat psoriasis on the scalp. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
LEO 80185 gel, calcipotriol 50 mcg/g plus betamethasone 0.5 mg/g (as dipropionate)
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Investigational medicinal product code |
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Other name |
LEO 80185 gel
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Pharmaceutical forms |
Gel
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Routes of administration |
Cutaneous use
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Dosage and administration details |
Applied once daily to lesions on the scalp, for up to 8 weeks
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Baseline characteristics reporting groups
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Reporting group title |
LEO 80185 Gel Once Daily Application
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Reporting group description |
Talconex® Scalp Topical Suspension/Daivobet® gel/Dovobet® gel/Xamiol® gel Calcipotriol 50 mcg/g plus betamethasone 0.5 mg/g (as dipropionate) gel once daily for up to 8 weeks to treat psoriasis on the scalp. | ||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
LEO 80185 Gel Once Daily Application
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Reporting group description |
Talconex® Scalp Topical Suspension/Daivobet® gel/Dovobet® gel/Xamiol® gel Calcipotriol 50 mcg/g plus betamethasone 0.5 mg/g (as dipropionate) gel once daily for up to 8 weeks to treat psoriasis on the scalp. | ||
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End point title |
Percentage of Subjects with Adverse Drug Reactions (ADRs) [1] | ||||||||
End point description |
Adverse events for which the investigator did not describe the causal relationship to IP as not related
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End point type |
Primary
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End point timeframe |
Throughout trial, up to 8 weeks
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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: There was no formal statistical hypothesis to be evaluated. The data were summarised using descriptive statistics. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in Albumin-corrected Serum Calcium From Baseline to Week 4 [2] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline to Week 4
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| Notes [2] - 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: There was no formal statistical hypothesis to be evaluated. The data were summarised using descriptive statistics. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in Albumin-corrected Serum Calcium From Baseline to Week 8 [3] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Basline and week 8
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| Notes [3] - 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: There was no formal statistical hypothesis to be evaluated. The data were summarised using descriptive statistics. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in Albumin-corrected Serum Calcium From Baseline to End of Treatment [4] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and End of treatment (up to 8 weeks)
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| Notes [4] - 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: There was no formal statistical hypothesis to be evaluated. The data were summarised using descriptive statistics. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in 24-hour Urinary Calcium Excretion From Baseline to Week 4 [5] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and week 4
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| Notes [5] - 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: There was no formal statistical hypothesis to be evaluated. The data were summarised using descriptive statistics. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in 24-hour Urinary Calcium Excretion From Baseline to Week 8 [6] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Basline and week 8
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| Notes [6] - 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: There was no formal statistical hypothesis to be evaluated. The data were summarised using descriptive statistics. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in 24-hour Urinary Calcium Excretion from Baseline to End of Treatment [7] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and End of Treatment (up to 8 weeks)
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| Notes [7] - 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: There was no formal statistical hypothesis to be evaluated. The data were summarised using descriptive statistics. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in Urinary Calcium:Creatinine Ratio From Baseline to End of Treatment [8] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Basline and End of Treatment
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| Notes [8] - 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: There was no formal statistical hypothesis to be evaluated. The data were summarised using descriptive statistics. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in Plasma parathyroid hormone (PTH) From Baseline to Week 4 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline and week 4
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in Plasma PTH From Baseline to Week 8 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline and week 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Subjects With Controlled Disease (i.e. Clear or Almost Clear) According to the Investigator's Global Assessment (IGA) of Disease Severity at Week 2 | ||||||||
End point description |
Disease severity of the scalp psoriasis as assessed by the 6-point scale IGA, based on the condition of the disease at the time of evaluation at week 2. The IGA Scale: 1 = clear, 2 = almost clear, 3 = mild, 4 = moderate, 5 = severe, and 6 = very severe.
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End point type |
Secondary
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End point timeframe |
Week 2
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| No statistical analyses for this end point | |||||||||
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End point title |
Subjects With Controlled Disease (i.e., Clear or Almost Clear) According to the Investigator’s Global Assessment (IGA) of Disease Severity at Week 4 | ||||||||
End point description |
Disease severity of the scalp psoriasis as assessed by the 6-point scale IGA, based on the condition of the disease at the time of evaluation at week 4
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End point type |
Secondary
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End point timeframe |
Week 4
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| No statistical analyses for this end point | |||||||||
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End point title |
Subjects With Controlled Disease (i.e., Clear or Almost Clear) According to the Investigator’s Global Assessment (IGA) of Disease Severity at Week 8 | ||||||||
End point description |
Disease severity of the scalp psoriasis as assessed by the 6-point scale IGA, based on the condition of the disease at the time of evaluation at week 8
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End point type |
Secondary
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End point timeframe |
Week 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Subjects With Controlled Disease (i.e., Clear or Almost Clear) According to the Investigator’s Global Assessment (IGA) of Disease Severity at End of Treatment | ||||||||
End point description |
Disease severity of the scalp psoriasis as assessed by the 6-point scale IGA, based on the condition of the disease at the time of evaluation at end of treatment
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End point type |
Secondary
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End point timeframe |
End of Treatment (up to 8 weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage Change in Total Sign Score (TSS; Sum of Severity Scores for Each Individual Clinical Sign, Redness, Thickness, and Scaliness)From Baseline to Week 2 | ||||||||
End point description |
Investigator assessment of scalp psoriasis lesions in terms of the three clinical signs: redness, thickness, and scaliness. Each clinical sign, a single score (ranging from 0 to 4), reflecting the average severity of all psoriatic lesions on the scalp, were determined. The sum of the three scores (redness, thickness, and scaliness) constitutes the Total Sign Score of the psoriasis on scalp, ranging from 0 (best possible outcome) to 12 points (worst possible outcome).
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End point type |
Secondary
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End point timeframe |
Baseline and Week 2
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage Change in Total Sign Score (TSS; Sum of Severity Scores for Each Individual Clinical Sign, Redness, Thickness, and Scaliness) From Baseline to Weeks 4 | ||||||||
End point description |
Investigator assessment of scalp psoriasis lesions in terms of the three clinical signs: redness, thickness, and scaliness. Each clinical sign, a single score (ranging from 0 to 4), reflecting the average severity of all psoriatic lesions on the scalp, were determined. The sum of the three scores (redness, thickness, and scaliness) constitutes the Total Sign Score of the psoriasis on scalp, ranging from 0 to 12 points.
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End point type |
Secondary
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End point timeframe |
Baseline and week 4
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage Change in Total Sign Score (TSS; Sum of Severity Scores for Each Individual Clinical Sign, Redness, Thickness, and Scaliness) From Baseline to Week 8 | ||||||||
End point description |
Investigator assessment of scalp psoriasis lesions in terms of the three clinical signs: redness, thickness, and scaliness. Each clinical sign, a single score (ranging from 0 to 4), reflecting the average severity of all psoriatic lesions on the scalp, were determined. The sum of the three scores (redness, thickness, and scaliness) constitutes the Total Sign Score of the psoriasis on scalp, ranging from 0 (best possible outcome) to 12 points (worst possible outcome).
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End point type |
Secondary
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End point timeframe |
Baseline and week 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage Change in Total Sign Score (TSS; Sum of Severity Scores for Each Individual Clinical Sign, Redness, Thickness, and Scaliness) From Baseline to End of Treatment. | ||||||||
End point description |
Investigator assessment of scalp psoriasis lesions in terms of the three clinical signs: redness, thickness, and scaliness. Each clinical sign, a single score (ranging from 0 to 4), reflecting the average severity of all psoriatic lesions on the scalp, were determined. The sum of the three scores (redness, thickness, and scaliness) constitutes the Total Sign Score of the psoriasis on scalp, ranging from 0 (best possible outcome) to 12 points (worst possible outcome).
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End point type |
Secondary
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End point timeframe |
Baseline and End of Treatment (up to 8 weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Subjects With Controlled Disease (Defined as Clear or Very Mild) According to the Patient’s Global Assessment of Disease Severity at Week 2 | ||||||||
End point description |
Disease severity of the scalp psoriasis as assessed by the 5-point scale, Patient's Global Assessment of Disease Severity, based on the condition of the disease at the time of evaluation. The scale: 1 = clear, 2 = very mild, 3 = mild, 4 = moderate, 5 = severe
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End point type |
Secondary
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End point timeframe |
Week 2
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| No statistical analyses for this end point | |||||||||
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End point title |
Subjects With Controlled Disease (Defined as Clear or Very Mild) According to the Patient’s Global Assessment of Disease Severity at Week 4 | ||||||||
End point description |
Disease severity of the scalp psoriasis as assessed by the 5-point scale, Patient's Global Assessment of Disease Severity, based on the condition of the disease at the time of evaluation.
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End point type |
Secondary
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End point timeframe |
Week 4
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| No statistical analyses for this end point | |||||||||
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End point title |
Subjects With Controlled Disease (Defined as Clear or Very Mild) According to the Patient’s Global Assessment of Disease Severity at Week 8 | ||||||||
End point description |
Disease severity of the scalp psoriasis as assessed by the 5-point scale, Patient's Global Assessment of Disease Severity, based on the condition of the disease at the time of evaluation.
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End point type |
Secondary
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End point timeframe |
Week 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Subjects With Controlled Disease (Defined as Clear or Very Mild) According to the Patient’s Global Assessment of Disease Severity at End of Treatment | ||||||||
End point description |
Disease severity of the scalp psoriasis as assessed by the 5-point scale, Patient's Global Assessment of Disease Severity, based on the condition of the disease at the time of evaluation.
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End point type |
Secondary
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End point timeframe |
End of Treatment (up to 8 weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Withdrawal | ||||||||
End point description |
How many subjects withdrew from the study. Reasons for withdrawal: due to exclusion criteria emerging, due to AE(s), or due to other reason
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End point type |
Secondary
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End point timeframe |
Week 4 and 8
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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 |
Throughout the trial, up to 8 weeks
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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 |
14.1
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Reporting groups
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Reporting group title |
LEO 80185 Gel Once Daily Application
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Reporting group description |
Talconex® Scalp Topical Suspension/Daivobet® gel/Dovobet® gel/Xamiol® gel Calcipotriol 50 mcg/g plus betamethasone 0.5 mg/g (as dipropionate) gel once daily for up to 8 weeks to treat psoriasis on the scalp. | ||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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09 Jun 2010 |
The duration of the wash-out period extended to up to 8 weeks (were up to 5 weeks), making the maximum duration of the trial period for each subject 20 weeks (were 17 weeks).
Informed consent for minors that became legally emancipated was added, so that a subject, who previously gave assent, during the trial became legally emancipated was to
be asked to provide their written consent. |
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11 Aug 2010 |
In the instruction to the Treatment Period the following was added: ‘Subjects should be instructed to discontinue treatment on individual lesions if/when a lesion has cleared’.
The following calculations from the 24-hour urine sample were added: calcium:creatinine, phophate:creatinine, hydroxyproline:creatinine, and sodium:creatinine ratios.
The wording of the definition of clear in erythema was clarified.
Cortisol was added to the biochemistry assessment.
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05 Jan 2011 |
Canada was added as a country.
Inclusion Criterion No. 6 was amended to ‘Clinical diagnosis of psoriasis vulgaris as evidenced by scalp psoriasis lesions of typical appearance or clinical signs of psoriasis vulgaris on trunk and/or limbs, or earlier diagnosed with psoriasis vulgaris on trunk and/or limbs.’
Inclusion Criterion No. 8 was amended to ‘Attending a hospital out-patient clinic or the private practice of a dermatologist or in the UK a General Practitioner with Special Interest in Dermatology (GPwSI).’ . |
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21 Nov 2011 |
The number of sites to include subjects were changed to 36 sites and Germany was added as a country (although no sites in Germany were used).
Exclusion Criterion No. 16 was amended to ‘Any clinically significant abnormality following review of screening laboratory tests (blood and spot urine samples, not including 24-hour urine sample), physical examination or blood pressure/heart rate measurement performed at SV2.’ ).
An Exclusion Criterion No. 23 was added: ‘Subjects who are institutionalised by court order or by the local authority.’
`The following were to be analysed quantitatively in the 24-hour urine sample: ` was added |
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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 | |||
