LEO 80185 Gel (Calcipotriol Hydrate Plus Betamethasone Dipropionate) in Japanese Subjects With Psoriasis

• Sponsor: LEO Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02668692
• Collaborator: CMIC Co, Ltd. Japan (Industry)
• Enrollment: 213
• Location: 1
• Arms: 2
• Duration (Months): 4
• Patients Per Site Per Month: 53.6

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
Psoriasis Vulgaris	Drug: LEO 80185 gel; Drug: Dovobet ® ointment	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

• Study Type: Interventional
• Actual Enrollment: 213 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of LEO 80185 Gel (Calcipotriol Hydrate Plus Betamethasone Dipropionate) in Japanese Subjects With Psoriasis Vulgaris
• Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

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

1. 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

1. 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.

2. 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

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 1. Informed consent has been obtained.
• 1. Japanese subjects
• 1. Aged 20 years or above
• 1. Clinical diagnosis of psoriasis vulgaris amenable to topical treatment of less than or equal to 30% BSA
• 1. 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).
• 1. 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.
• 1. Able to communicate with the (sub)investigator and understand and comply with the requirements of the trial.

Exclusion Criteria:

• 1. Systemic use of biological treatments with a potential effect on psoriasis vulgaris
• 1. Systemic treatments with all therapies other than biological treatments with a potential effect on psoriasis vulgaris
• 1. PUVA therapy, UVB therapy or UVA therapy
• 1. Topical treatment of psoriasis on the areas to be treated with trial medication
• 1. Topical treatment of psoriasis on the face, genitals or skin folds with vitamin D analogues, potent or very potent corticosteroids or immunosuppressants
• 1. Topical treatment of conditions other than psoriasis with vitamin D analogues, potent or very potent corticosteroids or immunosuppressants
• 1. Planned initiation of, or changes in, concomitant medication that may affect psoriasis vulgaris
• 1. 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.
• 1. Other inflammatory skin diseases that may confound the evaluation of psoriasis vulgaris.
• 1. Erythrodermic, exfoliative or pustular psoriasis
• 1. Planned excessive exposure of areas to be treated with trial medication to either natural or artificial sunlight
• 1. Known or suspected disorders of calcium metabolism associated with hypercalcaemia, or albumin-corrected serum calcium above the reference range
• 1. Known or suspected severe renal insufficiency, severe hepatic disorders or severe heart disease.
• 1. Known or suspected hypersensitivity to any components of the investigational products.
• 1. Clinical signs or symptoms of Cushing's disease or Addison's disease
• 1. Treatment with any non-marketed drug substance
• 1. Current participation in any other interventional clinical trial
• 1. Previously randomised in this trial
• 1. 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.

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT02668692
• Other Study ID Numbers: LP0076-1128
• First Posted: Jan 29, 2016
• Last Update Posted: Jul 27, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by LEO Pharma: LEO 80185 gel, calcipotriol, betamethasone
• Additional relevant MeSH terms: Psoriasis

Study Results

Participant Flow

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

1. Primary Outcome

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.

2. Secondary Outcome

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.

3. Secondary Outcome

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).
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

[Not Specified]

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.