Efficacy and Safety of Calcipotriol Plus Hydrocortisone Ointment in Psoriasis Vulgaris on the Face and Skin Folds
Study Details
Study Description
Brief Summary
There are few therapies suitable for the treatment of psoriasis on the face and skin folds. As these areas are sensitive, irritation and other adverse reactions are more common than elsewhere on the body. The purpose of the study is to compare the efficacy and safety of once daily treatment for up to 8 weeks of an ointment containing calcipotriol 25 mcg/g plus hydrocortisone 10 mg/g with calcipotriol 25 mcg/g in the ointment vehicle, hydrocortisone 10 mg/g in the ointment vehicle and the ointment vehicle alone in patients with psoriasis vulgaris on the face and on the intertriginous areas (= double-blind phase). Furthermore, the safety and efficacy will be evaluated for up to 60 weeks treatment as required of calcipotriol 25 mcg/g plus hydrocortisone 10 mg/g ointment in psoriasis vulgaris on the face and intertriginous areas (= open-label phase).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LEO 80190 Calcipotriol 25 mcg/g plus 10 mg/g hydrocortisone ointment (LEO 80190) |
Drug: Calcipotriol plus hydrocortisone (LEO 80190)
Once daily application
|
| Placebo Comparator: LEO 80190 vehicle Ointment Vehicle |
Drug: LEO 80190 Vehicle
|
| Active Comparator: Calcipotriol Calcipotriol 25 mcg/g in the ointment vehicle |
Drug: Calcipotriol
|
| Active Comparator: Hydrocortisone Hydrocortisone 10 mg/g in the ointment vehicle |
Drug: Hydrocortisone
|
Outcome Measures
Primary Outcome Measures
- Participants With "Controlled Disease" According to the Investigator's Global Assessment(IGA) of Disease Severity of the Face at Week 8 (Visit 6) in the Double-blind Phase [At Week 8 (end of treatment for double-blind phase)]
The (sub) investigator made an assessment of the disease severity of the face using the 6-category scale below. Clear, Almost clear, Mild, Moderate, Severe, Very severe The assessment was made considering the condition of psoriasis vulgaris of the face at the time of the evaluation, not in relation to the condition at a previous visit. For subjects with a baseline (Visit 1) severity of moderate or worse - "controlled disease" of the face was defined as clear or almost clear according to the IGA of disease severity of the face. For subjects with a baseline (Visit 1) severity of mild - "controlled disease" of the face was defined as clear according to the IGA of disease severity of the face.
Secondary Outcome Measures
- Participants With "Controlled Disease" According to the IGA of Disease Severity of the Face at Week 4 (Visit 4) in the Double-blind Phase [At Week 4]
The assessment of the disease severity of the face was made using the 6-category scale below. Clear Almost clear Mild Moderate Severe Very severe The assessment was made considering the condition of psoriasis vulgaris of the face at the time of the evaluation, not in relation to the condition at a previous visit. For subjects with a baseline severity of moderate or worse - "controlled disease" of the face was defined as clear or almost clear according to the IGA of disease severity of the face. For subjects with a baseline severity of mild - "controlled disease" of the face was defined as clear according to the IGA of disease severity of the face.
- Participants With "Success" According to Total Sign Score (TSS) of the Face at Week 8 (Visit 6) in the Double-blind Phase [At Week 8 (end of treatment for double-blind phase)]
"Success" was defined as a TSS score of 0 or 1. For each clinical sign, a single score, reflecting the average severity of all psoriatic lesions on the face was determined according to the scale below: Redness 0 = none (no erythema) 1 = mild (faint erythema, pink to very light red) 2 = moderate (definite light red erythema) 3 = severe (dark red erythema) 4 = very severe (very dark red erythema) Thickness 0 = none (no plaque elevation) 1 = mild (slight, barely perceptible elevation) 2 = moderate (definite elevation but not thick) 3 = severe (definite elevation, thick plaque with sharp edge) 4 = very severe (very thick plaque with sharp edge) Scaliness 0 = none (no scaling) 1 = mild (sparse, fine-scale lesions, only partially covered) 2 = moderate (coarser scales, most of lesions covered) 3 = severe (entire lesion covered with coarse scales) 4 = very severe (very thick coarse scales, possibly fissured) The sum of the three scores constituted a TSS ranging from 0 to 12
- Participants With "Controlled Disease" According to the IGA of Disease Severity of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase [At Week 8 (end of treatment for double-blind phase)]
The (sub)investigator made an assessment of the disease severity of the intertriginous areas using the 6-category scale below. Clear, Almost clear, Mild, Moderate, Severe, Very severe The assessment was made considering the condition of psoriasis vulgaris of the intertrigi-nous areas at the time of the evaluation, not in relation to the condition at a previous visit. For subjects with a baseline severity of moderate or worse - "controlled disease" of the intertriginous areas was defined as clear or almost clear according to the IGA of disease severity of the intertriginous areas. For subjects with a baseline severity of mild - "controlled disease" of the intertriginous areas was defined as clear according to the IGA of disease severity of the intertriginous areas.
- Participants With "Success" According to Total Sign Score of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase [At Week 8 (end of treatment for double-blind phase)]
The severity of the subject's psoriasis vulgaris on the intertriginous areas was evaluated in terms of the three clinical signs: redness, thickness and scaliness. All the defined intertriginous areas were rated separately using the same scale as for the investigator's assessment of clinical signs (redness, thickness and scaliness) of the face. For each clinical sign, a single score, reflecting the average severity of all psoriatic lesions on the face was determined according to the scale below: Redness 0 = none = mild = moderate = severe = very severe Thickness 0 = none = mild = moderate = severe = very severe Scaliness 0 = none = mild = moderate = severe = very severe A mean score was calculated for each sign (redness, thickness and scaliness) based on scores of all the defined intertriginous areas with psoriasis at baseline and the sum of these mean scores constituted the TSS. "Success" was defined as a TSS score of 0 or 1.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Clinical diagnosis of psoriasis vulgaris involving the face
-
Clinical signs of psoriasis vulgaris on the trunk and/or the limbs, or earlier diagnosed with psoriasis vulgaris on the trunk and/or the limbs
-
An extent of psoriatic involvement of the face of at least 10 cm2 (the sum of all facial lesions)
-
Treatment areas (the face and the intertriginous areas) amenable to topical treatment with a maximum of 100 g of ointment per week
-
Disease severity graded as mild, moderate, severe or very severe according to the investigator's global assessment of disease severity of the face
Exclusion Criteria:
-
Systemic treatments with all other therapies than biologicals, with a potential effect on psoriasis vulgaris (e.g., corticosteroids, vitamin D analogues, retinoids, immunosuppressants) within the 4-week period prior to randomisation
-
Systemic use of biological treatments, whether marketed or not, directed against or with a potential effect on psoriasis vulgaris (e.g., alefacept, efalizumab, etanercept, infliximab, adalimumab) within 3 months prior to randomisation
-
PUVA therapy or Grenz ray therapy within the 4-week period prior to randomisation
-
UVB therapy within the 2-week period prior to randomisation
-
Topical treatment of the face and the intertriginous areas within the 2-week period prior to randomisation (use of emollients is allowed on treatment areas during this 2-week period, but not during the double-blind phase of the study)
-
Topical treatment with very potent WHO group IV corticosteroids within the 2-week period prior to randomisation
-
Initiation of or expected changes in concomitant medication that may affect psoriasis vulgaris (e.g., beta blockers, anti-malaria drugs, lithium and ACE inhibitors) during the study
-
Current diagnosis of erythrodermic, exfoliative, guttate or pustular psoriasis
-
Patients with any of the following conditions present on the treatment area: viral (e.g., herpes or varicella) lesions of the skin, fungal and bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, rosacea, perioral dermatitis, acne vulgaris, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne rosacea, ulcers and wounds
-
Other inflammatory skin diseases (e.g., seborrhoiec dermatitis, contact dermatitis and cutaneous mycosis) that may confound the evaluation of psorisis vulgaris on the face or on the intertriginous areas
-
Planned exposure to sun, UVA or UVB that may affect the psoriasis vulgaris during the study
-
Known or suspected severe renal insufficiency or severe hepatic disorders
-
Known or suspected disorders of calcium metabolism associated with hypercalcaemia
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Croatia - managed by CRO | Zagreb | Croatia | 10000 | |
| 2 | Macedonia - managed by CRO | Zagreb | Croatia | 10000 | |
| 3 | Slovenia - managed by CRO | Zagreb | Croatia | 10000 | |
| 4 | Department of Dermatology and Allergy, University of Bonn | Bonn | Germany | 53105 | |
| 5 | Czech Republic - managed by CRO | Warszawa | Poland | 02-019 | |
| 6 | Hungary - managed by CRO | Warszawa | Poland | 02-019 | |
| 7 | Latvia - managed by CRO | Warszawa | Poland | 02-019 | |
| 8 | Poland - managed by CRO | Warszawa | Poland | 02-019 | |
| 9 | Belgium - managed by CRO | Warszawa | Poland | ||
| 10 | The Netherlands - managed by CRO | Warszawa | Poland | ||
| 11 | Serbia - managed by CRO | New Belgrade | Serbia | 11070 |
Sponsors and Collaborators
- LEO Pharma
Investigators
- Principal Investigator: Thomas Bieber, MD, Department of Dermatology and Allergy, University of Bonn
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- LEO 80190-O21
Study Results
Participant Flow
| Recruitment Details | A total of 1245 subjects were enrolled (informed consent signed and CRF started). Five subjects left the study during washout (2 screening failures, 2 lost to follow-up and 1 unacceptable adverse event). One subject attended Visit 1 but was not randomized (voluntary withdrawal). Therefore, 1239 of the enrolled subjects were randomized in the study. |
|---|---|
| Pre-assignment Detail | The Randomized double-blind phase of the study lasted up to 8 weeks, and was followed by a 52-week Open-label period in which participants had the opportunity to receive Calcipotriol 25 mcg/g plus 10 mg/g Hydrocortisone ointment. |
| Arm/Group Title | LEO 80190 | Calcipotriol | Hydrocortisone | LEO 80190 Vehicle | Open-label Phase |
|---|---|---|---|---|---|
| Arm/Group Description | Once daily application Calcipotriol 25 mcg/g plus 10 mg/g hydrocortisone ointment (LEO 80190) | Once daily application Calcipotriol 25 mcg/g in the ointment vehicle | Once daily application Hydrocortisone 10 mg/g in the ointment vehicle | Once daily application Ointment Vehicle | LEO 80190 ointment : calcipotriol 25 mcg/g plus 10 mg/g hydrocortisone ointment |
| Period Title: 8-week, Double-blind, 4-arm | |||||
| STARTED | 353 | 342 | 363 | 181 | 0 |
| COMPLETED | 325 | 308 | 340 | 169 | 0 |
| NOT COMPLETED | 28 | 34 | 23 | 12 | 0 |
| Period Title: 8-week, Double-blind, 4-arm | |||||
| STARTED | 454 | 0 | 0 | 0 | 0 |
| COMPLETED | 403 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 51 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | LEO 80190 | Calcipotriol | Hydrocortisone | LEO 80190 Vehicle | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Once daily application Calcipotriol 25 mcg/g plus 10 mg/g hydrocortisone ointment (LEO 80190) | Once daily application Calcipotriol 25 mcg/g in the ointment vehicle | Once daily application Hydrocortisone 10 mg/g in the ointment vehicle | Once daily application Ointment Vehicle | Total of all reporting groups |
| Overall Participants | 353 | 342 | 363 | 181 | 1239 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
42.8
(15.3)
|
44.8
(15.1)
|
43.0
(14.1)
|
44.6
(15.1)
|
43.6
(14.9)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
155
43.9%
|
139
40.6%
|
147
40.5%
|
76
42%
|
517
41.7%
|
| Male |
198
56.1%
|
203
59.4%
|
216
59.5%
|
105
58%
|
722
58.3%
|
| Region of Enrollment (participants) [Number] | |||||
| Belgium |
4
1.1%
|
6
1.8%
|
5
1.4%
|
2
1.1%
|
17
1.4%
|
| Croatia |
15
4.2%
|
13
3.8%
|
16
4.4%
|
7
3.9%
|
51
4.1%
|
| Czechia |
29
8.2%
|
22
6.4%
|
24
6.6%
|
15
8.3%
|
90
7.3%
|
| Germany |
99
28%
|
95
27.8%
|
96
26.4%
|
55
30.4%
|
345
27.8%
|
| Hungary |
58
16.4%
|
59
17.3%
|
64
17.6%
|
35
19.3%
|
216
17.4%
|
| Latvia |
23
6.5%
|
20
5.8%
|
24
6.6%
|
10
5.5%
|
77
6.2%
|
| Macedonia |
7
2%
|
8
2.3%
|
8
2.2%
|
3
1.7%
|
26
2.1%
|
| Netherlands |
4
1.1%
|
6
1.8%
|
5
1.4%
|
1
0.6%
|
16
1.3%
|
| Poland |
79
22.4%
|
76
22.2%
|
80
22%
|
37
20.4%
|
272
22%
|
| Serbia |
34
9.6%
|
36
10.5%
|
40
11%
|
16
8.8%
|
126
10.2%
|
| Slovenia |
1
0.3%
|
1
0.3%
|
1
0.3%
|
0
0%
|
3
0.2%
|
Outcome Measures
| Title | Participants With "Controlled Disease" According to the Investigator's Global Assessment(IGA) of Disease Severity of the Face at Week 8 (Visit 6) in the Double-blind Phase |
|---|---|
| Description | The (sub) investigator made an assessment of the disease severity of the face using the 6-category scale below. Clear, Almost clear, Mild, Moderate, Severe, Very severe The assessment was made considering the condition of psoriasis vulgaris of the face at the time of the evaluation, not in relation to the condition at a previous visit. For subjects with a baseline (Visit 1) severity of moderate or worse - "controlled disease" of the face was defined as clear or almost clear according to the IGA of disease severity of the face. For subjects with a baseline (Visit 1) severity of mild - "controlled disease" of the face was defined as clear according to the IGA of disease severity of the face. |
| Time Frame | At Week 8 (end of treatment for double-blind phase) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | LEO 80190 | Calcipotriol | Hydrocortisone | LEO 80190 Vehicle |
|---|---|---|---|---|
| Arm/Group Description | Once daily application Calcipotriol plus hydrocortisone (LEO 80190) | Once daily application Calcipotriol 25 mcg/g in the ointment vehicle | Once daily application Hydrocortisone 10 mg/g in the ointment vehicle | Once daily application Ointment Vehicle |
| Measure Participants | 353 | 341 | 363 | 180 |
| Count of Participants [Participants] |
158
44.8%
|
135
39.5%
|
115
31.7%
|
41
22.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LEO 80190, Calcipotriol |
|---|---|---|
| Comments | Test for superiority of LEO 80190 ointment versus calcipotriol ointment at Week 8 LOCF (Last Observation Carried Forward). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.11 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.28 | |
| Confidence Interval |
(2-Sided) 95% 0.94 to 1.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LEO 80190, Hydrocortisone |
|---|---|---|
| Comments | Test for superiority of LEO 80190 ointment versus hydrocortisone ointment at Week 8 LOCF (Last Observation Carried Forward). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.79 | |
| Confidence Interval |
(2-Sided) 95% 1.31 to 2.45 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | LEO 80190, LEO 80190 Vehicle |
|---|---|---|
| Comments | Test for superiority of LEO 80190 ointment versus ointment vehicle at Week 8 LOCF (Last Observation Carried Forward). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.70 | |
| Confidence Interval |
(2-Sided) 95% 1.80 to 4.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Participants With "Controlled Disease" According to the IGA of Disease Severity of the Face at Week 4 (Visit 4) in the Double-blind Phase |
|---|---|
| Description | The assessment of the disease severity of the face was made using the 6-category scale below. Clear Almost clear Mild Moderate Severe Very severe The assessment was made considering the condition of psoriasis vulgaris of the face at the time of the evaluation, not in relation to the condition at a previous visit. For subjects with a baseline severity of moderate or worse - "controlled disease" of the face was defined as clear or almost clear according to the IGA of disease severity of the face. For subjects with a baseline severity of mild - "controlled disease" of the face was defined as clear according to the IGA of disease severity of the face. |
| Time Frame | At Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | LEO 80190 | Calcipotriol | Hydrocortisone | LEO 80190 Vehicle |
|---|---|---|---|---|
| Arm/Group Description | Once daily application Calcipotriol plus hydrocortisone (LEO 80190) | Once daily application Calcipotriol 25 mcg/g in the ointment vehicle | Once daily application Hydrocortisone 10 mg/g in the ointment vehicle | Once daily application Ointment Vehicle |
| Measure Participants | 353 | 341 | 363 | 180 |
| Count of Participants [Participants] |
101
28.6%
|
66
19.3%
|
61
16.8%
|
14
7.7%
|
| Title | Participants With "Success" According to Total Sign Score (TSS) of the Face at Week 8 (Visit 6) in the Double-blind Phase |
|---|---|
| Description | "Success" was defined as a TSS score of 0 or 1. For each clinical sign, a single score, reflecting the average severity of all psoriatic lesions on the face was determined according to the scale below: Redness 0 = none (no erythema) 1 = mild (faint erythema, pink to very light red) 2 = moderate (definite light red erythema) 3 = severe (dark red erythema) 4 = very severe (very dark red erythema) Thickness 0 = none (no plaque elevation) 1 = mild (slight, barely perceptible elevation) 2 = moderate (definite elevation but not thick) 3 = severe (definite elevation, thick plaque with sharp edge) 4 = very severe (very thick plaque with sharp edge) Scaliness 0 = none (no scaling) 1 = mild (sparse, fine-scale lesions, only partially covered) 2 = moderate (coarser scales, most of lesions covered) 3 = severe (entire lesion covered with coarse scales) 4 = very severe (very thick coarse scales, possibly fissured) The sum of the three scores constituted a TSS ranging from 0 to 12 |
| Time Frame | At Week 8 (end of treatment for double-blind phase) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | LEO 80190 | Calcipotriol | Hydrocortisone | LEO 80190 Vehicle |
|---|---|---|---|---|
| Arm/Group Description | Once daily application Calcipotriol plus hydrocortisone (LEO 80190) | Once daily application Calcipotriol 25 mcg/g in the ointment vehicle | Once daily application Hydrocortisone 10 mg/g in the ointment vehicle | Once daily application Ointment Vehicle |
| Measure Participants | 353 | 341 | 363 | 180 |
| Count of Participants [Participants] |
171
48.4%
|
136
39.8%
|
131
36.1%
|
42
23.2%
|
| Title | Participants With "Controlled Disease" According to the IGA of Disease Severity of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase |
|---|---|
| Description | The (sub)investigator made an assessment of the disease severity of the intertriginous areas using the 6-category scale below. Clear, Almost clear, Mild, Moderate, Severe, Very severe The assessment was made considering the condition of psoriasis vulgaris of the intertrigi-nous areas at the time of the evaluation, not in relation to the condition at a previous visit. For subjects with a baseline severity of moderate or worse - "controlled disease" of the intertriginous areas was defined as clear or almost clear according to the IGA of disease severity of the intertriginous areas. For subjects with a baseline severity of mild - "controlled disease" of the intertriginous areas was defined as clear according to the IGA of disease severity of the intertriginous areas. |
| Time Frame | At Week 8 (end of treatment for double-blind phase) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | LEO 80190 | Calcipotriol | Hydrocortisone | LEO 80190 Vehicle |
|---|---|---|---|---|
| Arm/Group Description | Once daily application Calcipotriol plus hydrocortisone (LEO 80190) | Once daily application Calcipotriol 25 mcg/g in the ointment vehicle | Once daily application Hydrocortisone 10 mg/g in the ointment vehicle | Once daily application Ointment Vehicle |
| Measure Participants | 171 | 173 | 182 | 89 |
| Count of Participants [Participants] |
80
22.7%
|
55
16.1%
|
48
13.2%
|
14
7.7%
|
| Title | Participants With "Success" According to Total Sign Score of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase |
|---|---|
| Description | The severity of the subject's psoriasis vulgaris on the intertriginous areas was evaluated in terms of the three clinical signs: redness, thickness and scaliness. All the defined intertriginous areas were rated separately using the same scale as for the investigator's assessment of clinical signs (redness, thickness and scaliness) of the face. For each clinical sign, a single score, reflecting the average severity of all psoriatic lesions on the face was determined according to the scale below: Redness 0 = none = mild = moderate = severe = very severe Thickness 0 = none = mild = moderate = severe = very severe Scaliness 0 = none = mild = moderate = severe = very severe A mean score was calculated for each sign (redness, thickness and scaliness) based on scores of all the defined intertriginous areas with psoriasis at baseline and the sum of these mean scores constituted the TSS. "Success" was defined as a TSS score of 0 or 1. |
| Time Frame | At Week 8 (end of treatment for double-blind phase) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | LEO 80190 | Calcipotriol | Hydrocortisone | LEO 80190 Vehicle |
|---|---|---|---|---|
| Arm/Group Description | Once daily application Calcipotriol plus hydrocortisone (LEO 80190) | Once daily application Calcipotriol 25 mcg/g in the ointment vehicle | Once daily application Hydrocortisone 10 mg/g in the ointment vehicle | Once daily application Ointment Vehicle |
| Measure Participants | 171 | 173 | 182 | 89 |
| Count of Participants [Participants] |
82
23.2%
|
81
23.7%
|
59
16.3%
|
15
8.3%
|
Adverse Events
| Time Frame | Double-blind Phase: From baseline (Day 0) to end of trial (Day 56±2) + Follow-up (Day 14±2) Open-label Phase: From Week 8 to Week 60 ±7 days + Follow-up (Day 14±2) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The adverse events where collected for the the safety analysis set (SAS). The SAS consisted of those randomized patients who received any treatment with trial medication and for whom the presence or confirmed absence of adverse events were available. In total, 1235 subjects are included in the safety analysis set. | |||||||||
| Arm/Group Title | LEO 80190 | Calcipotriol | Hydrocortisone | LEO 80190 Vehicle | Open-label Phase | |||||
| Arm/Group Description | Once daily application Calcipotriol plus hydrocortisone (LEO 80190) | Once daily application Calcipotriol 25 mcg/g in the ointment vehicle | Once daily application Hydrocortisone 10 mg/g in the ointment vehicle | Once daily application Ointment Vehicle | LEO 80190 ointment : calcipotriol 25 mcg/g plus 10 mg/g hydrocortisone ointment | |||||
All Cause Mortality |
||||||||||
| LEO 80190 | Calcipotriol | Hydrocortisone | LEO 80190 Vehicle | Open-label Phase | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 0/453 (0%) | |||||
Serious Adverse Events |
||||||||||
| LEO 80190 | Calcipotriol | Hydrocortisone | LEO 80190 Vehicle | Open-label Phase | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/351 (1.4%) | 5/341 (1.5%) | 4/362 (1.1%) | 0/181 (0%) | 24/453 (5.3%) | |||||
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 0/351 (0%) | 1/341 (0.3%) | 0/362 (0%) | 0/181 (0%) | 0/453 (0%) | |||||
| Myocardial infarction | 1/351 (0.3%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Cardiac failure congestive | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Tinnitus | 1/351 (0.3%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 0/453 (0%) | |||||
| Vertigo | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Gastrointestinal disorders | ||||||||||
| Diverticulitis | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Nausea | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| General disorders | ||||||||||
| Chest pain | 0/351 (0%) | 0/341 (0%) | 1/362 (0.3%) | 0/181 (0%) | 0/453 (0%) | |||||
| Infections and infestations | ||||||||||
| Pneumonia | 0/351 (0%) | 1/341 (0.3%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Erysipelas | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 2/453 (0.4%) | |||||
| Gastroenteritis | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Deafness traumatic | 1/351 (0.3%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 0/453 (0%) | |||||
| Upper limb fracture | 1/351 (0.3%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 0/453 (0%) | |||||
| Cervical vertebra injury | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Clavicle fracture | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 2/453 (0.4%) | |||||
| Concussion | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Contusion | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 2/453 (0.4%) | |||||
| Excoriation | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthritis | 0/351 (0%) | 1/341 (0.3%) | 0/362 (0%) | 0/181 (0%) | 0/453 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Benign bone neoplasm | 0/351 (0%) | 1/341 (0.3%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Laryngeal neoplasm | 0/351 (0%) | 1/341 (0.3%) | 0/362 (0%) | 0/181 (0%) | 0/453 (0%) | |||||
| Cervix carcinoma stage 0 | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Chronic lymphocytic leukaemia | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Squamous cell carcinoma | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Nervous system disorders | ||||||||||
| Cerebrovascular accident | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Pregnancy, puerperium and perinatal conditions | ||||||||||
| Pregnancy | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 2/453 (0.4%) | |||||
| Psychiatric disorders | ||||||||||
| Depression | 0/351 (0%) | 0/341 (0%) | 1/362 (0.3%) | 0/181 (0%) | 0/453 (0%) | |||||
| Panic disorder | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Postmenopausal haemorrhage | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Psoriasis | 2/351 (0.6%) | 0/341 (0%) | 2/362 (0.6%) | 0/181 (0%) | 3/453 (0.7%) | |||||
| Surgical and medical procedures | ||||||||||
| Knee operation | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
| Vascular disorders | ||||||||||
| Hypertensive crisis | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 1/453 (0.2%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| LEO 80190 | Calcipotriol | Hydrocortisone | LEO 80190 Vehicle | Open-label Phase | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 91/351 (25.9%) | 100/341 (29.3%) | 70/362 (19.3%) | 47/181 (26%) | 266/453 (58.7%) | |||||
| Gastrointestinal disorders | ||||||||||
| Diarrhoea | 4/351 (1.1%) | 6/341 (1.8%) | 0/362 (0%) | 0/181 (0%) | 9/453 (2%) | |||||
| Toothache | 4/351 (1.1%) | 1/341 (0.3%) | 1/362 (0.3%) | 0/181 (0%) | 5/453 (1.1%) | |||||
| General disorders | ||||||||||
| Application site pruritus | 2/351 (0.6%) | 0/341 (0%) | 0/362 (0%) | 2/181 (1.1%) | 0/453 (0%) | |||||
| Pyrexia | 4/351 (1.1%) | 2/341 (0.6%) | 3/362 (0.8%) | 2/181 (1.1%) | 9/453 (2%) | |||||
| Infections and infestations | ||||||||||
| Herpes simplex | 4/351 (1.1%) | 0/341 (0%) | 1/362 (0.3%) | 0/181 (0%) | 0/453 (0%) | |||||
| Influenza | 3/351 (0.9%) | 2/341 (0.6%) | 2/362 (0.6%) | 2/181 (1.1%) | 10/453 (2.2%) | |||||
| Nasopharyngitis | 8/351 (2.3%) | 5/341 (1.5%) | 12/362 (3.3%) | 11/181 (6.1%) | 55/453 (12.1%) | |||||
| Bronchitis | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 6/453 (1.3%) | |||||
| Cystitis acute | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 5/453 (1.1%) | |||||
| Respiratory tract infection viral | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 9/453 (2%) | |||||
| Upper respiratory tract infection | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 6/453 (1.3%) | |||||
| Viral infection | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 5/453 (1.1%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 12/453 (2.6%) | |||||
| Back pain | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 8/453 (1.8%) | |||||
| Nervous system disorders | ||||||||||
| Burning sensation | 5/351 (1.4%) | 12/341 (3.5%) | 1/362 (0.3%) | 4/181 (2.2%) | 0/453 (0%) | |||||
| Headache | 11/351 (3.1%) | 6/341 (1.8%) | 8/362 (2.2%) | 2/181 (1.1%) | 17/453 (3.8%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Rhinitis | 4/351 (1.1%) | 1/341 (0.3%) | 4/362 (1.1%) | 0/181 (0%) | 13/453 (2.9%) | |||||
| Cough | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 10/453 (2.2%) | |||||
| Rhinitis allergic | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 8/453 (1.8%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Erythema | 7/351 (2%) | 24/341 (7%) | 7/362 (1.9%) | 7/181 (3.9%) | 13/453 (2.9%) | |||||
| Pruritus | 7/351 (2%) | 14/341 (4.1%) | 3/362 (0.8%) | 5/181 (2.8%) | 8/453 (1.8%) | |||||
| Psoriasis | 26/351 (7.4%) | 23/341 (6.7%) | 27/362 (7.5%) | 12/181 (6.6%) | 114/453 (25.2%) | |||||
| Skin irritation | 2/351 (0.6%) | 4/341 (1.2%) | 1/362 (0.3%) | 0/181 (0%) | 0/453 (0%) | |||||
| Vascular disorders | ||||||||||
| Hypertension | 0/351 (0%) | 0/341 (0%) | 0/362 (0%) | 0/181 (0%) | 7/453 (1.5%) | |||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Company acknowledges the investigators' right to publish the entire results of the study, irrespective of outcome. The Company retains the right to have any publication submitted to the Company for review at least 30 days prior to the same paper being submit-ted for publication or presentation. Investigators must undertake not to submit any part of their individual data for publication without the prior consent of LEO.
Results Point of Contact
| Name/Title | Clinical Trial Disclosure Manager |
|---|---|
| Organization | LEO Pharma A/S |
| Phone | +45 4494 5888 |
| disclosure@leo-pharma.com |
- LEO 80190-O21