Light Dose Ranging Study of Photodynamic Therapy (PDT) With Levulan + Blue Light Versus Vehicle + Blue Light in Severe Facial Acne

Acne Vulgaris Clinical Trial

Official title:

A Randomized, Evaluator-blinded, Parallel Group Light Dose Ranging Study of Photodynamic Therapy With Levulan Topical Solution + Blue Light Versus Levulan Topical Solution Vehicle + Blue Light on Moderate to Severe Facial Acne Vulgaris

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00706433
• Other study ID #: DUSA-CP0103
• Status: Completed
• Phase: Phase 2
• First received: June 24, 2008
• Last updated: October 20, 2011
• Start date: March 2007
• Est. completion date: July 2008

Study information

• Verified date: October 2011
• Source: DUSA Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine and compare the safety and efficacy of multiple broad area photodynamic therapy treatments with aminolevulinic acid (ALA-PDT) and vehicle (VEH-PDT) in subjects with moderate to severe facial acne vulgaris.

Description:

This is a Phase II multicenter, randomized, evaluator-blinded, vehicle-controlled, parallel group light dose ranging study of photodynamic therapy in subjects with moderate to severe facial acne vulgaris.

Subjects will be randomized to one of the following four treatment groups (1:1:1:1) to receive topical Levulan® Kerastick® containing 20% aminolevulinic acid HCL (ALA, active study drug) or the Kerastick® containing vehicle ingredients only (VEH).

• Group 1 will have ALA applied to the entire facial area 45 minutes ± 15 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds)

• Group 2 will have ALA applied to the entire facial area 45 minutes ± 15 minutes prior to BLUE light treatment for 500 seconds (8 minutes 20 seconds)

• Group 3 will have VEH applied to the entire facial area 45 minutes ± 15 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds)

• Group 4 will have VEH applied to the entire facial area 45 minutes ± 15 minutes prior to BLUE light treatment for 500 seconds (8 minutes 20 seconds)

Each subject may receive up to four treatments at three week (± 2 days) intervals. The power density (dose rate) and the total fluence (light dose) used at each treatment is intended to remain constant throughout each subject's participation. If a subject meets or exceeds the criteria restricting retreatment (CRR) prior to retreatment (Section 5.6), he/she will not receive additional PDT treatment at that visit and will be asked to return for the next scheduled PDT visit 3 weeks later, if applicable.

Post-treatment follow-up visits will be scheduled to occur at 3 and 6 weeks after the subject's final PDT.

Grading of the subject's facial acne will be conducted by a blinded evaluator who will remain blinded with respect to the subject's treatment assignment. Tolerability of treatment will be assessed by evaluations of the local skin response (erythema, edema, etc.) and will be conducted by an unblinded evaluator.

Safety will be evaluated by adverse events and local skin responses reported during the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 266
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Subject is male or non-pregnant female 12 years of age or older.

• Females must be post-menopausal, surgically sterile or using a medically acceptable form of birth control, with a negative urine pregnancy test at the Baseline visit.

• Subject has provided written and verbal informed consent. A subject under 18 years of age must be accompanied by the parent or legal guardian at the time of assent/consent signing. The parent or legal guardian must also provide informed consent for the subject.

• Subject has moderate to severe facial acne vulgaris (including the nose), with at least 20 inflammatory lesions (papules, pustules, nodules).

• Subject has moderate to severe acne as defined by an Investigator Global Assessment of 3 or 4 [0 (clear) to 4 (severe) scale].

• Subject has a history of recurrent herpes simplex labialis infection in the treatment area AND has had an outbreak within the last 12 months must be placed on antiviral prophylaxis as specified in the protocol.

• Subject is willing to comply with study instructions and return to the clinic for required visits.

• Subject must have used the same type and brand of make-up, other facial products and hair products (e.g. shampoo, gel, hair spray, mousse, etc.) for at least 1 month prior to the Baseline Visit (General Skin & Hair Care). Upon enrollment, all subjects must a) use exclusively an Investigator approved facial cleanser and b) agree to continue their other General Skin & Hair Care for the entire study.

Exclusion Criteria:

• Subject is pregnant, lactating, or is planning to become pregnant during the study.

• Subject has a history of cutaneous photosensitization, porphyria, hypersensitivity to porphyrins or photodermatosis.

• Subject has any skin pathology or condition that could interfere with the evaluation of the test product or requires the use of interfering topical or systemic therapy.

• Subject has greater than 4 facial nodules (nodule = lesion greater than or equal 0.5 cm in diameter)

• Subject has an uncorrected coagulation defect or concurrently uses anticoagulants (except aspirin).

• Subject has any condition which, in the investigator's opinion, would make it unsafe for the subject to participate in this research study.

• Subject is currently enrolled in an investigational drug or device study.

• Subject has received an investigational drug or been treated with an investigational device within 30 days prior to the initiation of treatment (baseline).

• Subject has facial hair that could interfere with the study assessments in the opinion of the investigator.

• Subject is unable to communicate or cooperate with the investigator due to language problems, poor mental development, or impaired cerebral function.

• Subject may be unreliable for the study including subjects who engage in excessive alcohol intake or drug abuse, or subjects who are unable to return for scheduled follow-up visits.

• Subject has a known sensitivity to one or more of the vehicle components (ethyl alcohol, isopropyl alcohol, laureth 4, polyethylene glycol).

• Subject has used photosensitizing drugs, e.g. declomycin, tetracycline, sulfa antibiotics, phenothiazines, etc. within a timeframe where photosensitization from these drugs may still be present.

• Subject has used OTC acne medicated cleansers or soaps within 2 weeks of the initiation of treatment.

• Subject has the need or plans to be exposed to artificial tanning devices or excessive sunlight during the trial.

• Subject has used any of the following topical anti-acne preparations on the face: a.) Topical anti-acne treatments including benzoyl peroxide, antibiotics, azelaic acid, corticosteroids and salicylic acid within 2 weeks of the initiation of treatment b.) Retinoids, including tazarotene, adapalene, tretinoin within 4 weeks of the initiation of treatment. c.) Light treatments, microdermabrasion or chemical peels within 8 weeks of the initiation of treatment.

• Subject has used any of the following systemic anti-acne medications: a.) Corticosteroids (including intramuscular and intralesional injections) within 4 weeks of the initiation of treatment. Inhaled corticosteroids are allowed if use is stable (stable use is defined as dose and frequency unchanged for at least 2 weeks prior to the initiation of treatment). b.) Antibiotics within 4 weeks of the initiation of treatment. c.) Nicotinamide containing products within 4 weeks of the initiation of treatment. d.) Spironolactone within 8 weeks of the initiation of treatment. d.) Retinoid therapy within 6 months of the initiation of treatment.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acne Vulgaris

Intervention

Drug:
• aminolevulinic acid HCL (ALA)
Levulan Kerastick containing 20% aminolevulinic acid HCL (ALA). Up to 4 treatments will be given at 3 week intervals.

Other:
• Vehicle (VEH)
Levulan Kerastick containing vehicle ingredients only (VEH). Up to 4 treatments will be given at 3 week intervals.

Locations

Country	Name	City	State
United States	Derm Research Inc	Austin	Texas
United States	Downstate Med Ctr	Brooklyn	New York
United States	Laser and Skin Surger Center of Indiana	Carmel	Indiana
United States	Baylor Research Institute	Dallas	Texas
United States	Cherry Creek Research, Inc.	Denver	Colorado
United States	Minnesota Clinical Study Center	Fridley	Minnesota
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Burke Pharmaceutical Research	Hot Springs	Arkansas
United States	Derm Research PLLC	Louisville	Kentucky
United States	Tennessee Clinical Research Center	Nashville	Tennessee
United States	Dermatology Research Center, Inc.	Salt Lake City	Utah
United States	Therapeutics Clinical Research	San Diego	California
United States	Gwinnett Clinical Research Center, Inc.	Snellville	Georgia
United States	Kenneth R. Beer, M.D. P.A.	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
DUSA Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Inflammatory Lesion Counts Relative to Baseline		Baseline and 3 weeks after final treatment	No
Primary	Investigator Global Assessment of Acne Severity Successes	Scale consists of Grade 0 (clear skin) to Grade 4 (severe: up to many non-inflammatory and inflammatory lesions, but no more than a few nodular lesions) This assessment uses a dichotomized success/failure assessment - with success defined as a 2 point or more improvement on the IGA scale since baseline.	Baseline and 3 weeks after final treatment	No
Secondary	Percent Change in Inflammatory Lesion Counts Relative to Baseline		Baseline and 3 weeks after final treatment	No
Secondary	Percent Change in Inflammatory Lesion Counts Relative to Baseline		Baseline and 6 weeks after final treatment	No
Secondary	Subject Satisfaction Score	Subject satisfaction score; = Excellent (very satisfied); = Good (moderately satisfied); = Fair (slightly satisfied); = Poor (not satisfied at all)	6 weeks after final treatment	No
Secondary	Change in Inflammatory Lesion Counts Relative to Baseline	change in lesion counts compared to baseline	Baseline and 6 weeks after final treatment	No
Secondary	Investigator Global Assessment of Acne Severity Successes	Assessment uses a dichotomized success/failure assessment with success defined as a 2 point or more improvement since baseline.; ?0 Clear skin with no inflam or non-inflam lesions; Almost clear; rare non-inflam lesions with no more than a few small inflam lesions; Mild; > Grade 1; some non-inflam lesions with some inflam lesions (papules/pustules only; no nodules); Moderate; > Grade 2; up to many non-inflam lesions and a moderate number of inflam lesions but no more than one small nodule; Severe; > Grade 3; up to many non-inflam and inflam lesions, but no more than a few nodules	Baesline and 6 weeks after final treatment	No
Secondary	Hyperpigmentation 48 Hours After PDT #1	? HYPERPIGMENTATION SCALE Grade 0 = No hyperpigmentation Grade 1 = Light hyperpigmentation involving small areas Grade 2 = Moderate hyperpigmentation involving small areas; light hyperpigmentation involving moderate areas Grade 3 = Moderate hyperpigmentation involving moderate sized areas; light hyperpigmentation involving large areas; small areas of marked hyperpigmentation Grade 4 = Marked hyperpigmentation involving moderate or large sized areas	48 hours after PDT #1	Yes
Secondary	Hyperpigmentation at Visit 3 (Week 3)	? HYPERPIGMENTATION SCALE Grade 0 = No hyperpigmentation Grade 1 = Light hyperpigmentation involving small areas Grade 2 = Moderate hyperpigmentation involving small areas; light hyperpigmentation involving moderate areas Grade 3 = Moderate hyperpigmentation involving moderate sized areas; light hyperpigmentation involving large areas; small areas of marked hyperpigmentation Grade 4 = Marked hyperpigmentation involving moderate or large sized areas	Visit 3 (Week 3)	Yes
Secondary	Hyperpigmentation at Visit 5 (Week 6)	? HYPERPIGMENTATION SCALE Grade 0 = No hyperpigmentation Grade 1 = Light hyperpigmentation involving small areas Grade 2 = Moderate hyperpigmentation involving small areas; light hyperpigmentation involving moderate areas Grade 3 = Moderate hyperpigmentation involving moderate sized areas; light hyperpigmentation involving large areas; small areas of marked hyperpigmentation Grade 4 = Marked hyperpigmentation involving moderate or large sized areas	Visit 5 (Week 6)	Yes
Secondary	Hyperpigmentation at Visit 7 (Week 9)	? HYPERPIGMENTATION SCALE Grade 0 = No hyperpigmentation Grade 1 = Light hyperpigmentation involving small areas Grade 2 = Moderate hyperpigmentation involving small areas; light hyperpigmentation involving moderate areas Grade 3 = Moderate hyperpigmentation involving moderate sized areas; light hyperpigmentation involving large areas; small areas of marked hyperpigmentation Grade 4 = Marked hyperpigmentation involving moderate or large sized areas	Visit 7 (Week 9)	Yes
Secondary	Hyperpigmentation at Visit 9 (3 Weeks After Final PDT)	? HYPERPIGMENTATION SCALE Grade 0 = No hyperpigmentation Grade 1 = Light hyperpigmentation involving small areas Grade 2 = Moderate hyperpigmentation involving small areas; light hyperpigmentation involving moderate areas Grade 3 = Moderate hyperpigmentation involving moderate sized areas; light hyperpigmentation involving large areas; small areas of marked hyperpigmentation Grade 4 = Marked hyperpigmentation involving moderate or large sized areas	Visit 9 (3 weeks after final PDT)	Yes
Secondary	Hyperpigmentation at Visit 10 (6 Weeks After Final PDT)	? HYPERPIGMENTATION SCALE Grade 0 = No hyperpigmentation Grade 1 = Light hyperpigmentation involving small areas Grade 2 = Moderate hyperpigmentation involving small areas; light hyperpigmentation involving moderate areas Grade 3 = Moderate hyperpigmentation involving moderate sized areas; light hyperpigmentation involving large areas; small areas of marked hyperpigmentation Grade 4 = Marked hyperpigmentation involving moderate or large sized areas	Visit 10 (6 weeks after final PDT)	Yes
Secondary	Hypopigmentation 48 Hours Post PDT #1	? HYPOPIGMENTATION SCALE Grade 0 = No hypopigmentation Grade 1 = Light hypopigmentation involving small areas Grade 2 = Moderate hypopigmentation involving small areas; light hypopigmentation involving moderate areas Grade 3 = Moderate hypopigmentation involving moderate sized areas; light hypopigmentation involving large areas; small areas of marked hypopigmentation Grade 4 = Marked hypopigmentation involving moderate or large sized areas	48 hours post PDT #1	Yes
Secondary	Hypopigmentation at Visit 3 (Week 3)	? HYPOPIGMENTATION SCALE Grade 0 = No hypopigmentation Grade 1 = Light hypopigmentation involving small areas Grade 2 = Moderate hypopigmentation involving small areas; light hypopigmentation involving moderate areas Grade 3 = Moderate hypopigmentation involving moderate sized areas; light hypopigmentation involving large areas; small areas of marked hypopigmentation Grade 4 = Marked hypopigmentation involving moderate or large sized areas	Visit 3 (Week 3)	Yes
Secondary	Hypopigmentation at Visit 5 (Week 6)	? HYPOPIGMENTATION SCALE Grade 0 = No hypopigmentation Grade 1 = Light hypopigmentation involving small areas Grade 2 = Moderate hypopigmentation involving small areas; light hypopigmentation involving moderate areas Grade 3 = Moderate hypopigmentation involving moderate sized areas; light hypopigmentation involving large areas; small areas of marked hypopigmentation Grade 4 = Marked hypopigmentation involving moderate or large sized areas	Visit 5 (Week 6)	Yes
Secondary	Hypopigmentation at Visit 7 (Week 9)	? HYPOPIGMENTATION SCALE Grade 0 = No hypopigmentation Grade 1 = Light hypopigmentation involving small areas Grade 2 = Moderate hypopigmentation involving small areas; light hypopigmentation involving moderate areas Grade 3 = Moderate hypopigmentation involving moderate sized areas; light hypopigmentation involving large areas; small areas of marked hypopigmentation Grade 4 = Marked hypopigmentation involving moderate or large sized areas	Visit 7 (Week 9)	Yes
Secondary	Hypopigmentation at Visit 9 (3 Weeks After Final PDT)	? HYPOPIGMENTATION SCALE Grade 0 = No hypopigmentation Grade 1 = Light hypopigmentation involving small areas Grade 2 = Moderate hypopigmentation involving small areas; light hypopigmentation involving moderate areas Grade 3 = Moderate hypopigmentation involving moderate sized areas; light hypopigmentation involving large areas; small areas of marked hypopigmentation Grade 4 = Marked hypopigmentation involving moderate or large sized areas	Visit 9 (3 weeks after final PDT)	Yes
Secondary	Hypopigmentation at Visit 10 (6 Weeks After Final PDT)	? HYPOPIGMENTATION SCALE Grade 0 = No hypopigmentation Grade 1 = Light hypopigmentation involving small areas Grade 2 = Moderate hypopigmentation involving small areas; light hypopigmentation involving moderate areas Grade 3 = Moderate hypopigmentation involving moderate sized areas; light hypopigmentation involving large areas; small areas of marked hypopigmentation Grade 4 = Marked hypopigmentation involving moderate or large sized areas	Visit 10 (6 weeks after final PDT)	Yes
Secondary	Erythema at Baseline (Pre-light)	After solution application, prior to light treatment; ? Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	Baseline (pre-light)	Yes
Secondary	Erythema at Baseline - Post Light Treatment	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	Baseline - post light treatment	Yes
Secondary	Erythema 48 Hours After PDT #1	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	48 hours after PDT #1	Yes
Secondary	Erythema at Visit 3 (Week 3 - Pre Study Drug Application)	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	Visit 3 (Week 3 - pre study drug application)	Yes
Secondary	Erythema at Visit 3 (Week 3 - Pre-light)	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	Visit 3 (Week 3 - pre-light)	Yes
Secondary	Erythema at Visit 3 (Week 3 - Post Light Treatment)	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	Visit 3 (Week 3 - post light treatment)	Yes
Secondary	Erythema at Visit 5 (Week 6 - Prior to Study Drug Application)	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	Visit 5 (Week 6 - prior to study drug application)	Yes
Secondary	Erythema at Visit 5 (Weeks 6 - Pre-light Treatment)	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	Visit 5 (Weeks 6 - pre-light treatment)	Yes
Secondary	Erythema at Visit 5 (Week 6 - Post Light Treatment)	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	Visit 5 (Week 6 - post light treatment)	Yes
Secondary	Erythema at Visit 7 (Week 9 - Prior to Study Drug Application)	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	Visit 7 (Week 9 - prior to study drug application)	Yes
Secondary	Erythema at Visit 7 (Week 9 - Pre Light Treatment)	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	Visit 7 (Week 9 - pre light treatment)	Yes
Secondary	Erythema at Visit 7 (Week 9 - Post Light Treatment)	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	Visit 7 (Week 9 - post light treatment)	Yes
Secondary	Erythema 3 Weeks After Final PDT	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	3 Weeks after Final PDT	Yes
Secondary	Erythema 6 Weeks After Final PDT	Grade 0 = None Grade 1 = Minimal - barely perceptible erythema Grade 2 = Mild - predominantly minimal erythema (pink) in the treated area with or without a few isolated areas of more intense erythema Grade 3 = Moderate - predominantly moderate erythema (red) in the treated area with or without a few isolated areas of intense erythema (bright red) Grade 4 = Severe - predominantly intense erythema (bright red) in the treated area with or without a few isolated areas of very intense (fiery red) erythema	6 Weeks after Final PDT	Yes
Secondary	Edema at Baseline - Pre Light Treatment	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	Baseline - pre light treatment	Yes
Secondary	Edema at Baseline - Post Light Treatment	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	Baseline - Post Light Treatment	Yes
Secondary	Edema 48 Hours After PDT #1	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	48 hours after PDT #1	Yes
Secondary	Edema at Visit 3 (Week 3 - Before Study Drug Application)	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	Visit 3 (Week 3 - before study drug application)	Yes
Secondary	Edema at Visit 3 (Week 3 - Before Light Treatment)	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	Visit 3 (Week 3 - before light treatment)	Yes
Secondary	Edema at Visit 3 (Week 3 - Post Light Treatment)	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	Visit 3 (Week 3 - post light treatment)	Yes
Secondary	Edema at Visit 5 (Week 6 - Before Study Drug Application)	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	Visit 5 (Week 6 - before study drug application)	Yes
Secondary	Edema at Visit 5 (Week 6 - Pre Light Treatment)	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	Visit 5 (Week 6 - pre light treatment)	Yes
Secondary	Edema at Visit 5 (Week 6 - Post Light Treatment)	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	Visit 5 (Week 6 - post light treatment)	Yes
Secondary	Edema at Visit 7 (Week 9 - Before Study Drug Application)	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	Visit 7 (Week 9 - before study drug application)	Yes
Secondary	Edema at Visit 7 (Week 9 - Prior to Light Treatment)	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	Visit 7 (Week 9 - prior to light treatment)	Yes
Secondary	Edema at Visit 7 (Week 9 - Post Light Treatment)	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	Visit 7 (Week 9 - post light treatment)	Yes
Secondary	Edema 3 Weeks After Final PDT	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	3 weeks after final PDT	Yes
Secondary	Edema 6 Weeks After Final PDT	?EDEMA SCALE Grade 0 = None Grade 1 = Minimal - scant, rare edema Grade 2 = Mild - easily seen edema, minimally palpable, involving up to 1/3 of the treatment area Grade 3 = Moderate - easily seen edema and typically palpable, involving between 1/3 to 2/3 of the treatment area Grade 4 = Severe - easily seen edema, indurated in some areas, involving over 2/3 of the treatment area	6 weeks after final PDT	Yes
Secondary	Stinging/Burning at Baseline - Before Light Treatment	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Baseline - before light treatment	Yes
Secondary	Stinging/Burning at Baseline - During Light	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Baseline - during light	Yes
Secondary	Stinging/Burning at Baseline - Post Light Treatment	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Baseline - post light treatment	Yes
Secondary	Stinging/Burning 48 Hours Post PDT #1	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	48 hours post PDT #1	Yes
Secondary	Stinging/Burning at Visit 3 (Week 3 - Before Study Drug Application)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 3 (Week 3 - before study drug application)	Yes
Secondary	Stinging/Burning at Visit 3 (Week 3 - Before Light Treatment)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 3 (Week 3 - before light treatment)	Yes
Secondary	Stinging/Burning at Visit 3 (Week 3 - During Light Treatment)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 3 (Week 3 - during light treatment)	Yes
Secondary	Stinging/Burning at Visit 3 (Week 3 - Post Light Treatment)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 3 (Week 3 - post light treatment)	Yes
Secondary	Stinging/Burning at Visit 5 (Week 6 - Before Study Drug Application)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 5 (Week 6 - before study drug application)	Yes
Secondary	Stinging/Burning at Visit 5 (Week 6 - Prior to Light Treatment)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 5 (Week 6 - prior to light treatment)	Yes
Secondary	Stinging/Burning at Visit 5 (Week 6 - During Light Treatment)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 5 (Week 6 - during light treatment)	Yes
Secondary	Stinging/Burning at Visit 5 (Week 6 - Post Light Treatment)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 5 (Week 6 - post light treatment)	Yes
Secondary	Stinging/Burning at Visit 7 (Week 9 - Before Study Drug Application)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 7 (Week 9 - before study drug application)	Yes
Secondary	Stinging/Burning at Visit 7 (Week 9 - Prior to Light Treatment)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 7 (Week 9 - prior to light treatment)	Yes
Secondary	Stinging/Burning at Visit 7 (Week 9 - During Light Treatment)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 7 (Week 9 - during light treatment)	Yes
Secondary	Stinging/Burning at Visit 7 (Week 9 - Post Light Treatment)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 7 (Week 9 - post light treatment)	Yes
Secondary	Stinging/Burning at Visit 9 (3 Weeks After Final PDT)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 9 (3 Weeks after Final PDT)	Yes
Secondary	Stinging/Burning at Visit 10 (6 Weeks After Final PDT)	?STINGING AND BURNING SCALE Grade 0 = None Grade 1 = Minimal, barely perceptible -tolerable and little discomfort Grade 2 = Moderate - tolerable, but causes some discomfort Grade 3 = Severe - very uncomfortable or intolerable	Visit 10 (6 Weeks after Final PDT)	Yes
Secondary	Scaling and Dryness 48 Hours After PDT #1	?SCALING AND DRYNESS SCALE Grade 0 = None Grade 1 = Minimal - barely perceptible desquamation Grade 2 = Mild - limited areas of fine desquamation in up to 1/3 of the treatment area Grade 3 = Moderate - fine desquamation involving 1/3 to 2/3 of the treatment area or limited areas of coarser scaling Grade 4 = Severe - coarser scaling involving more than 2/3 of the treatment area or limited areas of very coarse scaling	48 hours after PDT #1	Yes
Secondary	Scaling and Dryness at Visit 3 (Week 3)	?SCALING AND DRYNESS SCALE Grade 0 = None Grade 1 = Minimal - barely perceptible desquamation Grade 2 = Mild - limited areas of fine desquamation in up to 1/3 of the treatment area Grade 3 = Moderate - fine desquamation involving 1/3 to 2/3 of the treatment area or limited areas of coarser scaling Grade 4 = Severe - coarser scaling involving more than 2/3 of the treatment area or limited areas of very coarse scaling	Visit 3 (Week 3)	Yes
Secondary	Scaling and Dryness at Visit 5 (Week 6)	?SCALING AND DRYNESS SCALE Grade 0 = None Grade 1 = Minimal - barely perceptible desquamation Grade 2 = Mild - limited areas of fine desquamation in up to 1/3 of the treatment area Grade 3 = Moderate - fine desquamation involving 1/3 to 2/3 of the treatment area or limited areas of coarser scaling Grade 4 = Severe - coarser scaling involving more than 2/3 of the treatment area or limited areas of very coarse scaling	Visit 5 (Week 6)	Yes
Secondary	Scaling and Dryness at Visit 7 (Week 9)	?SCALING AND DRYNESS SCALE Grade 0 = None Grade 1 = Minimal - barely perceptible desquamation Grade 2 = Mild - limited areas of fine desquamation in up to 1/3 of the treatment area Grade 3 = Moderate - fine desquamation involving 1/3 to 2/3 of the treatment area or limited areas of coarser scaling Grade 4 = Severe - coarser scaling involving more than 2/3 of the treatment area or limited areas of very coarse scaling	Visit 7 (Week 9)	Yes
Secondary	Scaling and Dryness at Visit 9 (3 Weeks After Final PDT)	?SCALING AND DRYNESS SCALE Grade 0 = None Grade 1 = Minimal - barely perceptible desquamation Grade 2 = Mild - limited areas of fine desquamation in up to 1/3 of the treatment area Grade 3 = Moderate - fine desquamation involving 1/3 to 2/3 of the treatment area or limited areas of coarser scaling Grade 4 = Severe - coarser scaling involving more than 2/3 of the treatment area or limited areas of very coarse scaling	Visit 9 (3 Weeks after Final PDT)	Yes
Secondary	Scaling and Dryness at Visit 10 (6 Weeks After Final PDT)	?SCALING AND DRYNESS SCALE Grade 0 = None Grade 1 = Minimal - barely perceptible desquamation Grade 2 = Mild - limited areas of fine desquamation in up to 1/3 of the treatment area Grade 3 = Moderate - fine desquamation involving 1/3 to 2/3 of the treatment area or limited areas of coarser scaling Grade 4 = Severe - coarser scaling involving more than 2/3 of the treatment area or limited areas of very coarse scaling	Visit 10 (6 Weeks after Final PDT)	Yes
Secondary	Oozing/Vesiculation/Crusting 48 Hours After PDT #1	OOZING/VESICULATION/CRUSTING Grade 0 = None Grade 1 = Minimal - a single area of oozing, vesiculation or crusting 3 mm diameter or less in size Grade 2 = Mild - two to four areas of oozing, vesiculation or crusting 3 mm diameter or less in size OR a single area larger than 3 mm diameter in size Grade 3 = Moderate - more than a single area of oozing, vesiculation or crusting larger than 3 mm diameter in size or more than four areas of 3 mm diameter or less in size Grade 4 = Severe - any degree of oozing, vesiculation or crusting greater than (3) above	48 hours after PDT #1	Yes
Secondary	Oozing/Vesiculation/Crusting at Visit 3 (Week 3)	OOZING/VESICULATION/CRUSTING Grade 0 = None Grade 1 = Minimal - a single area of oozing, vesiculation or crusting 3 mm diameter or less in size Grade 2 = Mild - two to four areas of oozing, vesiculation or crusting 3 mm diameter or less in size OR a single area larger than 3 mm diameter in size Grade 3 = Moderate - more than a single area of oozing, vesiculation or crusting larger than 3 mm diameter in size or more than four areas of 3 mm diameter or less in size Grade 4 = Severe - any degree of oozing, vesiculation or crusting greater than (3) above	Visit 3 (Week 3)	Yes
Secondary	Oozing/Vesiculation/Crusting at Visit 5 (Week 6)	OOZING/VESICULATION/CRUSTING Grade 0 = None Grade 1 = Minimal - a single area of oozing, vesiculation or crusting 3 mm diameter or less in size Grade 2 = Mild - two to four areas of oozing, vesiculation or crusting 3 mm diameter or less in size OR a single area larger than 3 mm diameter in size Grade 3 = Moderate - more than a single area of oozing, vesiculation or crusting larger than 3 mm diameter in size or more than four areas of 3 mm diameter or less in size Grade 4 = Severe - any degree of oozing, vesiculation or crusting greater than (3) above	Visit 5 (Week 6)	Yes
Secondary	Oozing/Vesiculation/Crusting at Visit 7 (Week 9)	OOZING/VESICULATION/CRUSTING Grade 0 = None Grade 1 = Minimal - a single area of oozing, vesiculation or crusting 3 mm diameter or less in size Grade 2 = Mild - two to four areas of oozing, vesiculation or crusting 3 mm diameter or less in size OR a single area larger than 3 mm diameter in size Grade 3 = Moderate - more than a single area of oozing, vesiculation or crusting larger than 3 mm diameter in size or more than four areas of 3 mm diameter or less in size Grade 4 = Severe - any degree of oozing, vesiculation or crusting greater than (3) above	Visit 7 (Week 9)	Yes
Secondary	Oozing/Vesiculation/Crusting at Visit 9 (3 Weeks After Final PDT)	?OOZING/VESICULATION/CRUSTING Grade 0 = None Grade 1 = Minimal - a single area of oozing, vesiculation or crusting 3 mm diameter or less in size Grade 2 = Mild - two to four areas of oozing, vesiculation or crusting 3 mm diameter or less in size OR a single area larger than 3 mm diameter in size Grade 3 = Moderate - more than a single area of oozing, vesiculation or crusting larger than 3 mm diameter in size or more than four areas of 3 mm diameter or less in size Grade 4 = Severe - any degree of oozing, vesiculation or crusting greater than (3) above	Visit 9 (3 Weeks after Final PDT)	Yes
Secondary	Oozing/Vesiculation/Crusting at Visit 10 (6 Weeks After Final PDT)	?OOZING/VESICULATION/CRUSTING Grade 0 = None Grade 1 = Minimal - a single area of oozing, vesiculation or crusting 3 mm diameter or less in size Grade 2 = Mild - two to four areas of oozing, vesiculation or crusting 3 mm diameter or less in size OR a single area larger than 3 mm diameter in size Grade 3 = Moderate - more than a single area of oozing, vesiculation or crusting larger than 3 mm diameter in size or more than four areas of 3 mm diameter or less in size Grade 4 = Severe - any degree of oozing, vesiculation or crusting greater than (3) above	Visit 10 (6 Weeks after Final PDT)	Yes