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

Phase 2

Completed

Conditions: Keratosis, Actinic

Interventions: Drug: Aminolevulinic Acid (ALA)
Device: BLU-U

Registration Number: NCT02628236

Lead Sponsor: DUSA Pharmaceuticals, Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

Inclusion Criteria

At least 6 Grade 1/2 AKs on one upper extremity AND
At least 12 Grade 1/2 AKs on the OTHER upper extremity

Exclusion Criteria

Pregnancy
history of cutaneous photosensitization, porphyria, hypersensitivity to porphyrins or photodermatosis
lesions suspicious for skin cancer (skin cancer not ruled out by biopsy) or untreated skin cancers within the Treatment Area
Body Mass Index (BMI) > 32.0 kg/m2
skin pathology or condition which could interfere with the evaluation of the test product or requires the use of interfering topical or systemic therapy
significant blood loss within 60 days or donated blood/plasma within 72 hours prior to Visit 2 (Baseline)
tested positive at screening for human immunodeficiency virus (HIV) or was known to be seropositive for HIV
a history of lead poisoning or a history of a significant exposure to lead
tested positive at screening for hepatitis B surface antigen, hepatitis C antibody or had a history of a positive result
positive drug screen at Screening
Screening safety labs are clinically significant in the opinion of the investigator
major surgery within 30 days prior to Visit 2 (Baseline) or plans to have surgery during the study
Subject is immunosuppressed
currently enrolled in an investigational drug or device study
has received an investigational drug or been treated with an investigational device within 30 days prior to Visit 2 (Baseline)
known sensitivity to one or more of the vehicle components (ethyl alcohol, isopropyl alcohol, laureth 4, polyethylene glycol)
use of the following topical preparations on the extremities to be treated:
- Keratolytics including urea (greater than 5%), alpha hydroxyacids [e.g.glycolic acid, lactic acid, etc. greater than 5%], salicylic acid (greater than 2%) within 2 days of initiation of treatment
- Cryotherapy within 2 weeks of initiation of treatment
- Retinoids, including tazarotene, adapalene, tretinoin, retinol, within 4 weeks of initiation of treatment
- Microdermabrasion, laser ablative treatments, ALA-PDT, chemical peels, 5-FU, diclofenac, imiquimod or other topical treatments for AK within 8 weeks of initiation of treatment
use of systemic retinoid therapy within 6 months of initiation of treatment

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ALA	Aminolevulinic Acid (ALA)	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
ALA	BLU-U	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

Primary Outcome Measures

Name	Time	Method
AUCt	0, 15, 30 minutes, and 1, 2, 4, 8, 12, 16, 24 hours post-dose	AUCt is the area under the baseline corrected plasma concentration-time profile up to the last quantifiable/non-negative plasma concentration
The Terminal Exponential Half-life (T1/2,z) for ALA	2 days	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.
Time at Which Cmax is Attained (Tmax) for ALA	2 days	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.
Maximum Baseline Corrected Plasma Concentration (Cmax) for PpIX	2 days	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.
Maximum Baseline Corrected Plasma Concentration (Cmax) for ALA	2 days	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 at Which Cmax is Attained (Tmax) for PpIX	2 days	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.
AUCBL for PpIX	0, 15, 30 minutes, and 1, 2, 4, 8, 12, 16, 24, 36 and 48 hours post-dose	The area under the concentration time-curve assuming the baseline observed plasma concentration existed from time 0 to tlast.
AUCt for PpIX	0, 15, 30 minutes, and 1, 2, 4, 8, 12, 16, 24, 36 and 48 hours post-dose	The area under the observed plasma concentration time-curve from time 0 to the last quantifiable plasma concentration.
AUCt/AUCBL for PpIX	0, 15, 30 minutes, and 1, 2, 4, 8, 12, 16, 24, 36 and 48 hours post-dose	The ratio of AUCt to AUCBL for PpIX

Secondary Outcome Measures

Name	Time	Method
Edema	Week 4	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
OOZING/VESICULATION/CRUSTING	Week 4	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
Hyperpigmentation	Week 4	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	Week 4	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	Week 4	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
Scaling and Dryness	Week 4	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
Scaling and Dryness at Visit 4	24 hours after 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
Stinging/Burning	Week 4	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