Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Facies

Keratosis, Actinic

Keratosis

Skin Diseases

Precancerous Conditions

Dermatologic Agents

All Drugs and Chemicals

Aminolevulinic Acid

Photosensitizing Agents

Treatment 1 will include microneedling performed prior to ALA application to their right face and ALA application only to the left face 60 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds).

Treatment 2 will include microneedling performed prior to ALA application to their left face and ALA application only to the right side of their face 60 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds).

Treatment 3 will include microneedling performed prior to ALA application to their right face and ALA application only to the left side of their face 30 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds).

Treatment 4 will include microneedling performed prior to ALA application to their left face and ALA application only to the right side of their face 30 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds).

Aminolevulinic Acid (ALA)

Environ Cosmetic Roller

BLU-U IIlluminator

This is an investigator initiated, two center, randomized, evaluator-blinded, bilateral (right vs. left) study of photodynamic therapy in subjects with facial actinic keratoses.

Subject's face will be randomized to receive one of four treatments: Treatment 1, Treatment 2, Treatment 3 or Treatment 4. Treatment 1 will include microneedling performed prior to ALA application to their right face and ALA application only to the left face 60 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds). Treatment 2 will include microneedling performed prior to ALA application to their left face and ALA application only to the right side of their face 60 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds). Treatment 3 will include microneedling performed prior to ALA application to their right face and ALA application only to the left side of their face 30 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds). Treatment 4 will include microneedling performed prior to ALA application to their left face and ALA application only to the right side of their face 30 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds). The face is defined as the surface of the skin encompassing the forehead to the hair line and tops of the eyebrows, the entire nasal dorsum, the cheeks (bounded by the orbital rim, the anterior border of the ear, the jawline, the nose and the chin), the upper lip (not including the vermilion border) and the chin (bounded by the lower edge of the vermilion border, the cheek junction and the jawline). The treatment areas will be not be occluded. A line will be drawn with a marker that intersects the nose, forehead, upper lip and chin in the midline. The left face is defined as the face to the left of this line and the right face is defined as the face to the right of this line. Posttreatment follow-up visits will be scheduled to occur 48 hours after the treatment and at 1, 3 and 6 months after the treatment. A blinded evaluator who will remain blinded with respect to the randomization will conduct grading of the subject's actinic keratoses and photodamage. 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

Bilateral Comparison of Treatment of Facial Actinic Keratoses Using Microneedling and Photodynamic Therapy With Aminolevulinic Acid and Blue Light Versus Photodynamic Therapy With Aminolevulinic Acid and Blue Light Using Two Incubation Times

A Randomized, Evaluator-blinded, Bilateral Comparison of the Treatment of Facial Actinic Keratoses Using Combination Microneedling and Photodynamic Therapy With Aminolevulinic Acid and Blue Light Versus Photodynamic Therapy With Aminolevulinic Acid and Blue Light Using Two Different Incubation Times

Dermatology, Laser & Vein Specialists of the Carolinas

Pharmaceutical Solutions

20% ALA applied to upper extremities for 3 hours prior to 10 J/cm2 blue light

Levulan Kerastick containing vehicle ingredients only. Vehicle solution applied to upper extremities 3 hours prior to 10 J/cm2 blue light

Topical Solution Vehicle

10 J/cm2 blue light delivered at 10mW/cm2

Blue Light Photodynamic Therapy Illuminator (BLU-U)

Stuart Marcus, MD, PhD

The purpose of this study is to determine if Levulan Photodynamic Therapy (PDT) is safe and effective in the treatment of actinic keratoses on the upper arms and hands

Safety and Efficacy Study of Photodynamic Therapy With Levulan Kerastick + Blue Light for Actinic Keratoses on the Upper Extremities

A Phase 3 Study of Photodynamic Therapy With Levulan Kerastick Topical Solution + Blue Light Versus Topical Solution Vehicle + Blue Light for the Treatment of Actinic Keratoses on the Upper Extremities

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

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

Erythema Scale - 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

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

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

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

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

proportion of subjects in each treatment group with a count of zero lesions in the Treatment Area

{1 - \[(number of AK lesions at follow-up)/(number of AK lesions at Baseline)\]} x 100

Subject satisfaction score

1. = Excellent (very satisfied)
2. = Good (moderately satisfied)
3. = Fair (slightly satisfied)
4. = Poor (not satisfied at all)

DUSA Pharmaceuticals, Inc.

Aminolevulinic Acid (ALA): 20% ALA applied to upper extremities for 3 hours prior to 10 J/cm2 blue light

BLU-U Blue Light Photodynamic Therapy Illuminator: 10 J/cm2 blue light delivered at 10mW/cm2

ALA-PDT

Topical Solution Vehicle: Levulan Kerastick containing vehicle ingredients only. Vehicle solution applied to upper extremities 3 hours prior to 10 J/cm2 blue light

BLU-U Blue Light Photodynamic Therapy Illuminator: 10 J/cm2 blue light delivered at 10mW/cm2

Vehicle

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Type I

Type II

Type III

Type IV

Type V

Type VI

Fitzpatrick Skin Type I - Always burns easily; never tans (sensitive) II - Always burns easily; tans minimally (sensitive) III - Burns moderately; tans gradually (light brown) (normal) IV - Burns minimally, always tans well (moderate brown) (normal) V - Rarely burns; tans profusely (dark brown) (insensitive) VI - Never burns; deeply pigmented (insensitive)

Skin Type

Total Number AK Lesions (Grade 1/2)

Anna Houlihan

A hierarchical procedure was used to control the level of significance. If the primary analysis was sig (p≤0.05), then AKCR at Week 12 were to be compared. If this analysis was significant, then the AKCR at Week 8 were to be compared. If this analysis was significant, then the CCR at Week 8 was to be compared.

Complete Clearance Rate

AK Clearance Rate

Very Satisfied

Moderately Satisfied

Slightly Satisfied

Not Satisfied

Subject Satisfaction Score

Grade 0 (none)

Grade 1 (light)

Grade 2 (moderate - small)

Grade 3 (moderate - moderate)

Grade 4 (marked)

Hyperpigmentation

Hypopigmentation

Grade 1 (minimal)

Grade 2 (mild)

Grade 3 (moderate)

Grade 4 (severe)

Erythema

Edema

Grade 1 (mild)

Grade 2 (moderate)

Grade 3 (severe)

Stinging/Burning

Scaling & Dryness

Oozing/Vesiculation/Crusting

Overall Study

Vasodilator Agents

Platelet Aggregation Inhibitors

Urological Agents

Alprostadil

20% aminolevulinic acid applied via Kerastick to individual AK lesions on the upper extremities and covered with occlusive dressing for 3 hours prior to BLU-U treatment

10 J/cm2 of 417 nm blue light delivered at 10 mW/cm2

BLU-U

The purpose of this study is to evaluate the potential for systemic exposure of aminolevulinic acid (ALA) and protoporphyrin IX (PpIX) when applied topically under occlusion, in a maximal use setting in patients with multiple actinic keratoses (AK) involving the upper extremities.

Maximal Use Systemic Exposure Study of Levulan Kerastick (MUSE 2)

A Pharmacokinetic Study of Levulan Kerastick (Aminolevulinic Acid HCl) for Topical Solution, 20% Under Maximal Use Conditions

Maximum baseline corrected plasma concentration (Cmax) for ALA over the 24 hour sampling time period. Blood samples were taken before ALA application and at 15 and 30 minutes, 1, 2, 4, 8, 12, 16, 24, 36 and 48 hours following study medication application.

Time of the maximum baseline corrected plasma concentration for ALA measured at at 15 and 30 minutes, 1, 2, 4, 8, 12, 16, 24, 36 and 48 hours following study medication application.If a maximum value occurred at more than one timepoint Tmax is defined as the first timepoint with this value.

AUCt is the area under the baseline corrected plasma concentration-time profile up to the last quantifiable/non-negative plasma concentration

The terminal slope was calculated by linear least squares regression of the log plasma concentration-time data. The terminal exponential half-life (T1/2,z) will be calculated as 0.693 divided by the absolute value of slope.

Maximum baseline corrected plasma concentration (Cmax) for PpIX over the 48 hour sampling time period. Blood samples were taken before ALA application and at 15 and 30 minutes, 1, 2, 4, 8, 12, 16, 24, 36 and 48 hours following study medication application.

Time of the maximum baseline corrected plasma concentration for PpIX measured at at 15 and 30 minutes, 1, 2, 4, 8, 12, 16, 24, 36 and 48 hours following study medication application.If a maximum value occurred at more than one timepoint Tmax is defined as the first timepoint with this value.

The area under the concentration time-curve assuming the baseline observed plasma concentration existed from time 0 to tlast.

The area under the observed plasma concentration time-curve from time 0 to the last quantifiable plasma concentration.

20% aminolevulinic acid applied via Kerastick to individual AK lesions on the upper extremities and covered with occlusive dressing for 3 hours prior to BLU-U treatment

Aminolevulinic Acid (ALA): 20% ALA applied to upper extremities for 3 hours prior to 10 J/cm2 blue light

BLU-U: 10 J/cm2 of 417 nm blue light delivered at 10 mW/cm2

United States

Region of Enrollment

Maximum Baseline Corrected Plasma Concentration (Cmax) for ALA

Time at Which Cmax is Attained (Tmax) for ALA

AUCt

T1/2,z could not be determined in 11 subjects

The Terminal Exponential Half-life (T1/2,z) for ALA

For 50% of the subjects, more than 50% of the PpIX plasma concentrations following topical application of ALA HCI were less than the predose plasma concentration. Therefore, negative values were set to 0 to evaluate median baseline corrected plasma concentration.

Maximum Baseline Corrected Plasma Concentration (Cmax) for PpIX

One subject had tmax that could not be determined.

Time at Which Cmax is Attained (Tmax) for PpIX

AUCBL for PpIX

AUCt for PpIX

AUCt/AUCBL for PpIX

Scaling and Dryness

Scaling and Dryness at Visit 4

OOZING/VESICULATION/CRUSTING

BLU-U Blue Light Photodynamic Therapy Illuminator

The purpose of this study is to determine the long-term safety and efficacy of Levulan PDT in subjects with multiple actinic keratosis of the upper extremities who received treatment as part of the DUSA CP0108 study.

Twelve Month Follow-Up of CP0108

Twelve Month Follow-Up Evaluation of Subjects Participating in DUSA-CP0108 (A Phase 3 Study of Photodynamic Therapy With Levulan Kerastick Topical Solution + Blue Light Versus Topical Solution Vehicle + Blue Light for the Treatment of Actinic Keratoses on the Upper Extremities)

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

percentage of subjects who had achieved 100% clearance at Visit 6 (Week 12) in CP0108, that have one or more previously treated (as part of CP0108) AK lesion(s) present in the Treatment Area at any visit during CP0108A follow-up

the time from Week 12 (in the DUSA-CP0108 study) to the visit at which a previously treated and cleared lesion recurs. If a subject begins or receives treatment for previously cleared AK lesions in the Treatment Area between scheduled visits, the date the treatment started will be the end of treatment response, or, if the start date is unknown, the visit prior to starting the new treatment will be the end of treatment response.

the proportion of lesions that were CR at Week 12 in CP0108 that are visible or palpable at Visit 10, will be determined for all ALA-PDT treated subjects who have at least one AK designated as "clear" at Week 12 in the DUSA-CP0108 study.

the time from Week 12 (in the DUSA-CP0108 study) to the visit at which the AK lesion recurs for all ALA-PDT treated subjects who have at least one AK designated as "clear" at Week 12 in the DUSA-CP0108 study. If a previously cleared lesion receives treatment between scheduled visits, the date the treatment started will be the end of treatment response for that lesion, or, if the start date is unknown, the visit prior to starting the new treatment will be the end of treatment response.

The purpose of this study is to evaluate the potential for systemic exposure of aminolevulinic acid (ALA) when applied topically under occlusion, in a maximal use setting in patients with multiple actinic keratoses (AK) involving the upper extremities.

Maximal Use Systemic Exposure (MUSE) Study of Levulan Kerastick

Maximum baseline corrected plasma concentration (Cmax) for ALA over the 24 hour sampling time period. Blood samples wiere taken before ALA application and at 15 and 30 minutes, 1, 2, 4, 8, 12, 16 and 24 hours following study medication application.

Time of the maximum baseline corrected plasma concentration for ALA measured at at 15 and 30 minutes, 1, 2, 4, 8, 12, 16 and 24 hours following study medication application.If a maximum value occurred at more than one timepoint Tmax is defined as the first timepoint with this value.

The terminal slope will be calculated by linear least squares regression of the log plasma concentration-time data. The terminal exponential half-life (T1/2,z) will be calculated as 0.693 divided by the absolute value of slope.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bilateral Comparison of Treatment of Facial Actinic Keratoses Using Microneedling and Photodynamic Therapy With Aminolevulinic Acid and Blue Light Versus Photodynamic Therapy With Aminolevulinic Acid and Blue Light Using Two Incubation Times	NCT02622594	Actinic Keratos...	Aminolevulinic ... Environ Cosmeti... BLU-U IIllumina...	18 Years -	Dermatology, Laser & Vein Specialists of the Carolinas
Safety and Efficacy Study of Photodynamic Therapy With Levulan Kerastick + Blue Light for Actinic Keratoses on the Upper Extremities	NCT02137785	Actinic Keratos...	Aminolevulinic ... Topical Solutio... Blue Light Phot...	18 Years -	DUSA Pharmaceuticals, Inc.
Maximal Use Systemic Exposure Study of Levulan Kerastick (MUSE 2)	NCT02628236	Keratosis, Acti...	Aminolevulinic ... BLU-U	18 Years -	DUSA Pharmaceuticals, Inc.
Twelve Month Follow-Up of CP0108	NCT02209012	Actinic Keratos...	Aminolevulinic ... Topical Solutio... BLU-U Blue Ligh...	18 Years -	DUSA Pharmaceuticals, Inc.
Maximal Use Systemic Exposure (MUSE) Study of Levulan Kerastick	NCT02281136	Keratosis, Acti...	Aminolevulinic ... BLU-U	18 Years -	DUSA Pharmaceuticals, Inc.
Maximal Use Systemic Exposure (MUSE) Study of Levulan Kerastick	NCT02281136	Keratosis, Acti...	Aminolevulinic ... BLU-U	18 Years -	DUSA Pharmaceuticals, Inc.
Maximal Use Systemic Exposure Study of Levulan Kerastick (MUSE 2)	NCT02628236	Keratosis, Acti...	Aminolevulinic ... BLU-U	18 Years -	DUSA Pharmaceuticals, Inc.
Bilateral Comparison of Treatment of Facial Actinic Keratoses Using Microneedling and Photodynamic Therapy With Aminolevulinic Acid and Blue Light Versus Photodynamic Therapy With Aminolevulinic Acid and Blue Light Using Two Incubation Times	NCT02622594	Actinic Keratos...	Aminolevulinic ... Environ Cosmeti... BLU-U IIllumina...	18 Years -	Dermatology, Laser & Vein Specialists of the Carolinas

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