Oral Lichen Planus
Conditions
Keywords
oral lichen planus, pimecrolimus 1% cream
Brief summary
Study investigating the use of pimecrolimus 1% cream for oral lichen planus
Detailed description
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.
Interventions
pimecrolimus cream or matching placebo BID for 6 weeks
Sponsors
Novartis
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Efficacy Variable Was the Change in the Investigator's Global Assessment of the Overall Severity of Disease From Baseline to Week 6. | 0, 1, 2, 4, 6 weeks | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Secondary Efficacy Variables Was Changes Erythema and Assessment of Spontaneous Pain on a Visual Analog Scale (0-10). | 0, 1, 2, 4, 6 weeks | 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). |
| The Secondary Efficacy Variable Was Change in the Size of a Target Erosion in Millimeters. | 0, 1, 2, 4, 6 weeks | Secondary outcome variable was change in size of the target erosion in millimeters from baseline compared to week 6. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pimecrolimus 1% Cream 0.25 grams of pimecrolimus 1% cream applied to each of the two sides of the mouth twice daily with a 2x2 inch piece of gauze folded in half and placed directly on the lesion for 5 minutes | 10 |
| Vehicle Cream 0.25 grams of vehicle cream (identical in composition and appearance to pimecrolimus 1% cream without active product) applied to each of the two sides of the mouth twice daily with a 2x2 inch piece of gauze folded in half and placed directly on the lesion for 5 minutes | 11 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Pimecrolimus 1% Cream | Vehicle Cream | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 10 | 7 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 11 |
Outcome results
Primary
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).
Time frame: 0, 1, 2, 4, 6 weeks
Population: ITT using last observation carried forward for missing data
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pimecrolimus Cream | The Primary Efficacy Variable Was the Change in the Investigator's Global Assessment of the Overall Severity of Disease From Baseline to Week 6. | baseline | 2.4 units on a scale |
| Pimecrolimus Cream | The Primary Efficacy Variable Was the Change in the Investigator's Global Assessment of the Overall Severity of Disease From Baseline to Week 6. | week 6 | 1.6 units on a scale |
| Vehicle Cream | The Primary Efficacy Variable Was the Change in the Investigator's Global Assessment of the Overall Severity of Disease From Baseline to Week 6. | baseline | 2.45 units on a scale |
| Vehicle Cream | The Primary Efficacy Variable Was the Change in the Investigator's Global Assessment of the Overall Severity of Disease From Baseline to Week 6. | week 6 | 2.27 units on a scale |
Secondary
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).
Time frame: 0, 1, 2, 4, 6 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pimecrolimus Cream | The Secondary Efficacy Variables Was Changes Erythema and Assessment of Spontaneous Pain on a Visual Analog Scale (0-10). | mean erythema baseline | 2 units on a scale |
| Pimecrolimus Cream | The Secondary Efficacy Variables Was Changes Erythema and Assessment of Spontaneous Pain on a Visual Analog Scale (0-10). | mean erythema week 6 | 1 units on a scale |
| Pimecrolimus Cream | The Secondary Efficacy Variables Was Changes Erythema and Assessment of Spontaneous Pain on a Visual Analog Scale (0-10). | mean pain baseline | 3 units on a scale |
| Pimecrolimus Cream | The Secondary Efficacy Variables Was Changes Erythema and Assessment of Spontaneous Pain on a Visual Analog Scale (0-10). | mean pain week 6 | 2 units on a scale |
| Vehicle Cream | The Secondary Efficacy Variables Was Changes Erythema and Assessment of Spontaneous Pain on a Visual Analog Scale (0-10). | mean pain week 6 | 3 units on a scale |
| Vehicle Cream | The Secondary Efficacy Variables Was Changes Erythema and Assessment of Spontaneous Pain on a Visual Analog Scale (0-10). | mean erythema baseline | 2 units on a scale |
| Vehicle Cream | The Secondary Efficacy Variables Was Changes Erythema and Assessment of Spontaneous Pain on a Visual Analog Scale (0-10). | mean pain baseline | 4 units on a scale |
| Vehicle Cream | The Secondary Efficacy Variables Was Changes Erythema and Assessment of Spontaneous Pain on a Visual Analog Scale (0-10). | mean erythema week 6 | 1 units on a scale |
Secondary
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.
Time frame: 0, 1, 2, 4, 6 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pimecrolimus Cream | The Secondary Efficacy Variable Was Change in the Size of a Target Erosion in Millimeters. | mean erosion baseline | 11 mm |
| Pimecrolimus Cream | The Secondary Efficacy Variable Was Change in the Size of a Target Erosion in Millimeters. | mean erosion week 6 | 4 mm |
| Vehicle Cream | The Secondary Efficacy Variable Was Change in the Size of a Target Erosion in Millimeters. | mean erosion baseline | 33 mm |
| Vehicle Cream | The Secondary Efficacy Variable Was Change in the Size of a Target Erosion in Millimeters. | mean erosion week 6 | 21 mm |