Maximal Use Systemic Exposure (MUSE) Study of Levulan Kerastick

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

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.

Study Overview

• Status: Completed
• Conditions: Keratosis, Actinic
• Intervention / Treatment: Drug: Aminolevulinic Acid (ALA); Device: BLU-U

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Therapeutics Clinical Research
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Shideler Clinical Research Center
  • Texas
    • Austin, Texas, United States, 78759
      • Dermresearch, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 or a screening lead level above 6μg/dl
• 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 Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Aminolevulinic Acid (ALA); 20% ALA applied to upper extremities for 3 hours prior to 10 J/cm2 blue light; Other Names: Levulan Kerastick; Device: BLU-U; 10 J/cm2 of 417 nm blue light delivered at 10 mW/cm2; Other Names: Blue Light Photodynamic Therapy (PDT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCt	AUCt is the area under the baseline corrected plasma concentration-time profile up to the last quantifiable/non-negative plasma concentration	0, 15, 30 minutes, and 1, 2, 4, 8, 12, 16, 24 hours post-dose
Maximum Baseline Corrected Plasma Concentration (Cmax) for ALA	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.	1 day
Time at Which Cmax is Attained (Tmax) for ALA	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.	1 day
The Terminal Exponential Half-life (T1/2,z)	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.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hyperpigmentation	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	Baseline
Erythema	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	Baseline
Edema	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
Stinging/Burning	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
Hypopigmentation	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	Baseline
Hyperpigmentation	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	24 hours after PDT
Hyperpigmentation	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	Week 4
Hypopigmentation	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	Week 4
Erythema	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	5 Minutes after PDT
Erythema	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	Week 4
Edema	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	5 Minutes after PDT
Edema	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	Week 4
Stinging/Burning	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	Week 4
Scaling and Dryness	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	Baseline
Scaling and Dryness	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	Week 4
OOZING/VESICULATION/CRUSTING	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	Baseline
OOZING/VESICULATION/CRUSTING	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	Week 4
Erythema	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	24 hours after PDT #1
Edema	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	24 hours after PDT #1
Hypopigmentation	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	24 hours post PDT#1
Stinging/Burning	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	During PDT
Stinging/Burning	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	5 Minutes after PDT
Stinging/Burning	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	24 hours after PDT #1
Scaling and Dryness	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	24 hours after PDT #1
OOZING/VESICULATION/CRUSTING	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	24 hours after PDT #1

Collaborators and Investigators

• Sponsor: DUSA Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: October 30, 2014
• First Submitted That Met QC Criteria: October 31, 2014
• First Posted (Estimate): November 2, 2014

Study Record Updates

• Last Update Posted (Estimate): January 13, 2017
• Last Update Submitted That Met QC Criteria: November 16, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Actinic keratosis
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid
• Other Study ID Numbers: CP0110