Pimecrolimus Cream for Oral Lichen Planus

Study Overview
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Brief Summary
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Study investigating the use of pimecrolimus 1% cream for oral lichen planus

Detailed Description
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Lichen planus (LP) is an idiopathic inflammatory dermatosis of the skin and mucous membranes. Cutaneous lesions present as pink polygonal papules on the flexor wrists, trunk, thighs, shin and the dorsal hands. Oral lichen planus (OLP) represents a unique subset of LP and is often the sole manifestation of this disease. Clinically, the lesions can be reticulate, erythematous, atrophic or erosive, with the erosive form being the most common. Lesions can be found anywhere in the oral mucosa and are associated with burning pain which is worsened while eating. The risk of development of squamous cell carcinoma has been estimated to be as high as 5%. Treatments for oral lichen planus involve high potency topical steroid, systemic steroids, oral/topical retinoids and immunosuppressants. However, the long term side effects of steroids (e.g. striae, skin atrophy, telangiectasias, tachyphylaxis, secondary candidiasis and perioral dermatitis) prevent more extensive utilization except in the most severe cases. Given the debilitating nature of OLP, risk of malignant transformation, and long term side effects associated with current therapies, a safe intervention is needed for this disorder. Tacrolimus and pimecrolimus may have fewer side affects than topical steroids. Recently, in an open label trial of 19 patients with recalcitrant erosive lichen planus, tacrolimus decreased the area of ulceration by 73% after an eight week course. Local irritation was the most common side effect. However, tacrolimus comes in an ointment base, a poorly tolerated vehicle for oral lesions. Topical treatment of oral lesions has also been compromised by problems with maintaining sufficient contact time between poorly adherent cream and ointment preparations and moist mucous membrane surfaces. This study is designed to evaluate the topical application of pimecrolimus 1% cream when applied twice daily with occlusion in the treatment of oral lichen planus.

Official Title
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A 6-week Randomized, Double-blind, Vehicle-controlled Pilot Study With a 6-week Open Label Extension to Assess the Efficacy and Safety of Pimecrolimus 1% Cream in the Treatment of Oral Lichen Planus

Conditions
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Oral Lichen Planus

Intervention / Treatment
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* Drug: Pimecrolimus 1% cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Of any gender, 18 years or older. With a diagnosis of oral lichen planus previously proven on biopsy. With at least one erosion at baseline (baseline IGA of 2 or greater). Signed written informed consent. Willingness and ability to comply with the study requirements. Negative blood pregnancy tests must be documented for all females of childbearing potential prior to enrollment. Exclusion Criteria: Who have received systemic immunosuppressants (e.g. corticosteroids), or oral retinoids, or any other systemic therapies known or suspected to have an effect on oral lichen planus within 4 weeks prior to participation in the study. Who have been treated with topical therapy (e.g., topical corticosteroids, pimecrolimus, tacrolimus, or topical retinoids, etc) or any other topical therapies known or suspected to have an effect on oral lichen planus within two weeks prior to participation in the study. Who are immunocompromised (e.g., lymphoma, AIDS, Wiskott-Aldrich Syndrome) or have an evidence of malignant disease. Who have systemic or generalized infections (bacterial, viral or fungal). Who have a clinically relevant liver disorder (transaminase enzymes >3 x ULN) or renal disorder (serum creatinine > 10% above upper normal limit). Who have unstable or uncontrolled diabetes or hypertension. Who are currently receiving or are intended to be treated with any potent inhibitor of the enzyme CYP450 3A4. Treatment with substrates or moderately potent inhibitors of CYP450 3A4 is permitted during the study, under close monitoring for adverse events during that period. Menstruating females of childbearing potential who are not using a medically accepted method of contraception during the study. Medically approved contraception may, at the discretion of the investigator, include abstinence. Women who are breastfeeding. Who had received an investigational drug within four weeks prior to the study or who intended to use other investigational drugs during the course of this study. Who are hypersensitive to pimecrolimus or any of the components of the cream. Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study. Who have a history of substance abuse or any factor, which limits the subject's ability to cooperate with the study procedures. Who are uncooperative, known to miss appointments (according to subjects' records) and are unlikely to follow medical instructions or are not willing to attend regular visits. History of Netherton's syndrome Patients with lymphadenopathy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>During the 6-week double-blind phase, all patients will be randomly assigned to receive either pimecrolimus 1% cream or its vehicle twice daily with occlusion on the affected areas. Topical application of pimecrolimus1% cream for oral erosive lichen planus for a duration of 6 weeks; ¼ gram of cream will be applied to each of the 2 sides of the mouth BID with a 2x2 gauze. | Drug: Pimecrolimus 1% cream<br>* pimecrolimus cream or matching placebo BID for 6 weeks<br>* Other names: elidel cream;|
| Placebo Comparator: 2<br>During the 6-week double-blind phase, all patients will be randomly assigned to receive either pimecrolimus 1% cream or its vehicle twice daily with occlusion on the affected areas. Topical application of pimecrolimus1% cream for oral erosive lichen planus for a duration of 6 weeks; ¼ gram of cream will be applied to each of the 2 sides of the mouth BID with a 2x2 gauze. | Drug: Pimecrolimus 1% cream<br>* pimecrolimus cream or matching placebo BID for 6 weeks<br>* Other names: elidel cream;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Efficacy Variable Was the Change in the Investigator's Global Assessment of the Overall Severity of Disease From Baseline to Week 6. | The primary efficacy variable was the change in the Investigator's Global Assessment of the overall severity of disease from baseline to week 6. Scale is 0-4. 0 is no disease. 4 is worst disease. Minimum score is 0. Maximum score is 4. Measurments were completed day 0, week 1, week 2, week 4, and week 6. Scores are listed at baseline (day 0) and end of study (week 6). | 0, 1, 2, 4, 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Secondary Efficacy Variables Was Changes Erythema and Assessment of Spontaneous Pain on a Visual Analog Scale (0-10). | The secondary efficacy variables were change in the size of the target erosion, erythema and assessment of spontaneous pain on a visual analog scale (0-10). The scale used to measure erythema is 0-3. 0 is no erythema, 1 is mild erythema, 2 is moderate erythema, and 3 is severe erythema. Minimum score is 0. Maximum score is 3. Spontaneous pain was scored on a scale of 0-10 (0 no pain, 10 severe pain). Measurments were completed day 0, week 1, week 2, week 4, and week 6. Scores are listed at baseline (day 0) and end of study (week 6). | 0, 1, 2, 4, 6 weeks | 
| The Secondary Efficacy Variable Was Change in the Size of a Target Erosion in Millimeters. | Secondary outcome variable was change in size of the target erosion in millimeters from baseline compared to week 6. | 0, 1, 2, 4, 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oral lichen planus, pimecrolimus 1% cream