LEO 80185 Gel (Calcipotriol Hydrate Plus Betamethasone Dipropionate) in Japanese Subjects With Psoriasis
Study Details
Study Description
Brief Summary
To compare the efficacy and safety of LEO 80185 gel with Dovobet® ointment in the treatment of psoriasis in Japanese subjects.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Detailed Description
A phase 3, national, multi-centre, 4-week, prospective, randomised, controlled, parallel-group, open trial of LEO 80185 gel versus Dovobet® ointment in Japanese subjects with psoriasis vulgaris.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: LEO 80185 gel
|
Drug: LEO 80185 gel
calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions
|
Active Comparator: Dovobet ® ointment
|
Drug: Dovobet ® ointment
calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions
|
Outcome Measures
Primary Outcome Measures
- Number of Subjects With 'Overall Improvement' for the Target Lesion on the Scalp [End of Week 4]
'Overall improvement' for the target lesion on the scalp, defined as 'substantial resolution' of clinical signs and/or at least 'moderately improved' in the general change in the lesion. 'Substantial resolution' is defined as a clinical score for thickness and scaliness of 0 and a clinical score for redness of 1 or less in the severity of clinical signs of the lesion.
Secondary Outcome Measures
- Number of Subjects With 'Overall Improvement' for the Target Lesion on the Non-scalp Area of the Body [End of Week 4]
'Overall Improvement' for the target lesion on the non-scalp area of the body, defined as 'substantial resolution' of clinical signs and/or at least 'moderately improved' in the general change in the lesion. 'Substantial resolution' is defined as a clinical score for thickness and scaliness of 0 and a clinical score for redness of 1 or less in the severity of clinical signs of the lesion.
- The Change in the Sum of the Scores (Total Sign Score) for the Severity of the 3 Clinical Signs:Thickness, Scaliness, Redness From Baseline to End of Week 4 (Visit 1-4) for Each Target Lesion. [From Baseline to end of Week 4 (Visit 1-4)]
Severity was recorded for each of the 3 clinical signs according to the 9-point scales* below. *intermediate intervals (0.5, 1.5, 2.5, 3.5) serve as mid points between the defined grades. Redness 0=none (no erythema) slight (faint erythema, pink to very light red) mild (definite light red erythema) moderate (dark red erythema) severe (very dark red erythema) Thickness 0=none (no plaque elevation) slight (slight, barely perceptible elevation) mild (definite elevation but not thick) moderate (definite elevation, thick plaque with sharp edge) severe (very thick plaque with sharp edge) Scaliness 0=none (no scaling) slight (sparse, fine scale, lesions only partially covered) mild (coarser scales, most of lesions covered) moderate (entire lesion covered with coarse scales) severe (very thick coarse scales, possibly fissured) Negative change denotes a decrease in the score and therefore a decrease in disease severity.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
- Informed consent has been obtained.
-
- Japanese subjects
-
- Aged 20 years or above
-
- Clinical diagnosis of psoriasis vulgaris amenable to topical treatment of less than or equal to 30% BSA
-
- A target psoriasis lesion on the scalp and on the non-scalp area of the body, each lesion of a minimum size of 10 cm2 and scoring at least 2 (mild) for each of the clinical signs (redness, thickness and scaliness).
-
- Females of childbearing potential must have a negative result for a urine pregnancy test at Day 1 (Visit 1) and must agree to use an adequate method of birth control.
-
- Able to communicate with the (sub)investigator and understand and comply with the requirements of the trial.
Exclusion Criteria:
-
- Systemic use of biological treatments with a potential effect on psoriasis vulgaris
-
- Systemic treatments with all therapies other than biological treatments with a potential effect on psoriasis vulgaris
-
- PUVA therapy, UVB therapy or UVA therapy
-
- Topical treatment of psoriasis on the areas to be treated with trial medication
-
- Topical treatment of psoriasis on the face, genitals or skin folds with vitamin D analogues, potent or very potent corticosteroids or immunosuppressants
-
- Topical treatment of conditions other than psoriasis with vitamin D analogues, potent or very potent corticosteroids or immunosuppressants
-
- Planned initiation of, or changes in, concomitant medication that may affect psoriasis vulgaris
-
- Patients with any of the following disorders (a) or symptoms (b) present on the areas to be treated with trial medication: (a) viral (e.g., herpes or varicella) lesions of the skin, fungal, spirochetal or bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, rosacea, acne vulgaris, atrophic skin, striae atrophicae, ichthyosis, acne rosacea, ulcers, burns, frostbite, wounds, animal skin disease (scabies, crabs, lice, etc.) or (b) fragility of skin veins.
-
- Other inflammatory skin diseases that may confound the evaluation of psoriasis vulgaris.
-
- Erythrodermic, exfoliative or pustular psoriasis
-
- Planned excessive exposure of areas to be treated with trial medication to either natural or artificial sunlight
-
- Known or suspected disorders of calcium metabolism associated with hypercalcaemia, or albumin-corrected serum calcium above the reference range
-
- Known or suspected severe renal insufficiency, severe hepatic disorders or severe heart disease.
-
- Known or suspected hypersensitivity to any components of the investigational products.
-
- Clinical signs or symptoms of Cushing's disease or Addison's disease
-
- Treatment with any non-marketed drug substance
-
- Current participation in any other interventional clinical trial
-
- Previously randomised in this trial
-
- Females who are pregnant, wishing to become pregnant or are breast-feeding
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Medical Corporation Bikyukai Kokubu Dermatology | Kitami-shi | Hokkaido | Japan | 090-0832 |
Sponsors and Collaborators
- LEO Pharma
- CMIC Co, Ltd. Japan
Investigators
- Principal Investigator: Hidemi Nakagawa, MD, Department of Dermatology, Jikei University School of Medicine, Tokyo, Japan
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- LP0076-1128
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | The trial had 213 participants enrolled and 206 participants randomized. |
Arm/Group Title | LEO 80185 Gel | Dovobet® Ointment |
---|---|---|
Arm/Group Description | LEO 80185 gel: calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions | Dovobet® ointment: calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions |
Period Title: Overall Study | ||
STARTED | 101 | 105 |
COMPLETED | 100 | 105 |
NOT COMPLETED | 1 | 0 |
Baseline Characteristics
Arm/Group Title | LEO 80185 Gel | Dovobet® Ointment | Total |
---|---|---|---|
Arm/Group Description | LEO 80185 gel: calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions | Dovobet® ointment: calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions | Total of all reporting groups |
Overall Participants | 101 | 105 | 206 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
51.0
(13.7)
|
54.3
(14.2)
|
52.7
(14.0)
|
Sex: Female, Male (Count of Participants) | |||
Female |
67
66.3%
|
84
80%
|
151
73.3%
|
Male |
34
33.7%
|
21
20%
|
55
26.7%
|
Region of Enrollment (Count of Participants) | |||
Japan |
101
100%
|
105
100%
|
206
100%
|
Outcome Measures
Title | Number of Subjects With 'Overall Improvement' for the Target Lesion on the Scalp |
---|---|
Description | 'Overall improvement' for the target lesion on the scalp, defined as 'substantial resolution' of clinical signs and/or at least 'moderately improved' in the general change in the lesion. 'Substantial resolution' is defined as a clinical score for thickness and scaliness of 0 and a clinical score for redness of 1 or less in the severity of clinical signs of the lesion. |
Time Frame | End of Week 4 |
Outcome Measure Data
Analysis Population Description |
---|
All 206 randomised subjects are included in the full analysis set (FAS): 101 in the LEO 80185 group and 105 in the Dovobet® group. The per protocol analysis set (PPAS) was defined by excluding subjects from the FAS based on a review of protocol deviations. PPAS includes 94 subjects in the LEO 80185 group and 100 in the Dovobet® group. |
Arm/Group Title | LEO 80185 Gel | Dovobet® Ointment |
---|---|---|
Arm/Group Description | LEO 80185 gel: calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions | Dovobet® ointment: calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions |
Measure Participants | 101 | 105 |
Overall improvement |
99
98%
|
101
96.2%
|
Not overall improvement |
2
2%
|
4
3.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | LEO 80185 Gel, Dovobet® Ointment |
---|---|---|
Comments | Statistical analysis of the FAS. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.68 |
Comments | ||
Method | Fisher Exact | |
Comments | ||
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 1.96 | |
Confidence Interval |
(2-Sided) 95% 0.35 to 10.95 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | LEO 80185 Gel, Dovobet® Ointment |
---|---|---|
Comments | Statistical analysis of the PPAS. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.68 |
Comments | Treatment comparison by Fisher's exact test. | |
Method | Fisher Exact | |
Comments | ||
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 1.92 | |
Confidence Interval |
(2-Sided) 95% 0.34 to 10.72 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Odds of 'overall improvement' in LEO 80185 gel group relative to Dovobet® ointment group. |
Title | Number of Subjects With 'Overall Improvement' for the Target Lesion on the Non-scalp Area of the Body |
---|---|
Description | 'Overall Improvement' for the target lesion on the non-scalp area of the body, defined as 'substantial resolution' of clinical signs and/or at least 'moderately improved' in the general change in the lesion. 'Substantial resolution' is defined as a clinical score for thickness and scaliness of 0 and a clinical score for redness of 1 or less in the severity of clinical signs of the lesion. |
Time Frame | End of Week 4 |
Outcome Measure Data
Analysis Population Description |
---|
All 206 randomised subjects are included in the full analysis set (FAS): 101 in the LEO 80185 group and 105 in the Dovobet® group. The per protocol analysis set (PPAS) was defined by excluding subjects from the FAS based on a review of protocol deviations. PPAS includes 94 subjects in the LEO 80185 group and 100 in the Dovobet® group. |
Arm/Group Title | LEO 80185 Gel | Dovobet® Ointment |
---|---|---|
Arm/Group Description | LEO 80185 gel: calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions | Dovobet® ointment: calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions |
Measure Participants | 101 | 105 |
Overall improvement |
83
82.2%
|
99
94.3%
|
Not overall improvement |
18
17.8%
|
6
5.7%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | LEO 80185 Gel, Dovobet® Ointment |
---|---|---|
Comments | Statistical analysis for the FAS. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.009 |
Comments | ||
Method | Fisher Exact | |
Comments | ||
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 0.28 | |
Confidence Interval |
(2-Sided) 95% 0.11 to 0.74 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | LEO 80185 Gel, Dovobet® Ointment |
---|---|---|
Comments | Statistical analysis of the PPAS. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.003 |
Comments | Treatment comparison by Fisher's exact test. | |
Method | Fisher Exact | |
Comments | ||
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 0.22 | |
Confidence Interval |
(2-Sided) 95% 0.08 to 0.63 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Odds of 'overall improvement' in LEO 80185 gel group relative to Dovobet® ointment group. |
Title | The Change in the Sum of the Scores (Total Sign Score) for the Severity of the 3 Clinical Signs:Thickness, Scaliness, Redness From Baseline to End of Week 4 (Visit 1-4) for Each Target Lesion. |
---|---|
Description | Severity was recorded for each of the 3 clinical signs according to the 9-point scales* below. *intermediate intervals (0.5, 1.5, 2.5, 3.5) serve as mid points between the defined grades. Redness 0=none (no erythema) slight (faint erythema, pink to very light red) mild (definite light red erythema) moderate (dark red erythema) severe (very dark red erythema) Thickness 0=none (no plaque elevation) slight (slight, barely perceptible elevation) mild (definite elevation but not thick) moderate (definite elevation, thick plaque with sharp edge) severe (very thick plaque with sharp edge) Scaliness 0=none (no scaling) slight (sparse, fine scale, lesions only partially covered) mild (coarser scales, most of lesions covered) moderate (entire lesion covered with coarse scales) severe (very thick coarse scales, possibly fissured) Negative change denotes a decrease in the score and therefore a decrease in disease severity. |
Time Frame | From Baseline to end of Week 4 (Visit 1-4) |
Outcome Measure Data
Analysis Population Description |
---|
The per protocol analysis set (PPAS) was defined by excluding subjects from the full analysis set (FAS) based on a review of protocol deviations. PPAS includes 94 subjects in the LEO 80185 group and 100 in the Dovobet® group. |
Arm/Group Title | LEO 80185 Gel | Dovobet® Ointment |
---|---|---|
Arm/Group Description | LEO 80185 gel: calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions | Dovobet® ointment: calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions |
Measure Participants | 94 | 100 |
Scalp (PPAS) |
-6.43
(1.91)
|
-6.79
(1.90)
|
Non-scalp (PPAS) |
-5.31
(2.44)
|
-6.46
(2.05)
|
Adverse Events
Time Frame | From signing of Informed Consent Form up to 14 days after last visit (Week 4). | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | LEO 80185 Gel | Dovobet® Ointment | ||
Arm/Group Description | LEO 80185 gel: calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions | Dovobet® ointment: calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g, applied once daily to psoriasis lesions | ||
All Cause Mortality |
||||
LEO 80185 Gel | Dovobet® Ointment | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/101 (0%) | 0/105 (0%) | ||
Serious Adverse Events |
||||
LEO 80185 Gel | Dovobet® Ointment | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/101 (1%) | 0/105 (0%) | ||
Infections and infestations | ||||
Meningitis | 1/101 (1%) | 1 | 0/105 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
LEO 80185 Gel | Dovobet® Ointment | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 13/101 (12.9%) | 9/105 (8.6%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 1/101 (1%) | 1 | 1/105 (1%) | 1 |
Leukocytosis | 1/101 (1%) | 1 | 0/105 (0%) | 0 |
Eye disorders | ||||
Glaucoma | 1/101 (1%) | 1 | 0/105 (0%) | 0 |
Gastrointestinal disorders | ||||
Chelitis | 0/101 (0%) | 0 | 1/105 (1%) | 1 |
Stomatitis | 0/101 (0%) | 0 | 1/105 (1%) | 1 |
General disorders | ||||
Oedema peripheral | 1/101 (1%) | 1 | 0/105 (0%) | 0 |
Infections and infestations | ||||
Folliculitis | 2/101 (2%) | 2 | 1/105 (1%) | 1 |
Herpes zoster | 1/101 (1%) | 1 | 0/105 (0%) | 0 |
Influenza | 0/101 (0%) | 0 | 1/105 (1%) | 1 |
Kaposi's varicelliform eruption | 1/101 (1%) | 1 | 0/105 (0%) | 0 |
Nasopharyngitis | 3/101 (3%) | 3 | 2/105 (1.9%) | 2 |
Ophthalmic herpes simplex | 1/101 (1%) | 1 | 0/105 (0%) | 0 |
Tinea pedis | 1/101 (1%) | 1 | 0/105 (0%) | 0 |
Injury, poisoning and procedural complications | ||||
Overdose | 0/101 (0%) | 0 | 1/105 (1%) | 1 |
Investigations | ||||
Blood bilirubin increased | 0/101 (0%) | 0 | 1/105 (1%) | 1 |
Glucose urine present | 2/101 (2%) | 2 | 0/105 (0%) | 0 |
Platelet count decreased | 0/101 (0%) | 0 | 1/105 (1%) | 1 |
White blood cell count increased | 0/101 (0%) | 0 | 1/105 (1%) | 1 |
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 1/101 (1%) | 1 | 0/105 (0%) | 0 |
Arthritis | 1/101 (1%) | 1 | 0/105 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||
Alopecia areata | 1/101 (1%) | 1 | 0/105 (0%) | 0 |
Seborrhoeic dermatitis | 1/101 (1%) | 1 | 0/105 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title | Clinical Trial Disclosure Manager |
---|---|
Organization | LEO Pharma A/S |
Phone | |
disclosure@leo-pharma.com |
- LP0076-1128