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

• ClinicalTrials.gov Identifier: NCT02628236
• Recruitment Status: Completed
• First Posted: December 11, 2015
• Results First Posted: September 18, 2017
• Last Update Posted: September 18, 2017
• Sponsor: DUSA Pharmaceuticals, Inc.
• Information provided by (Responsible Party): DUSA Pharmaceuticals, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Keratosis, Actinic	Drug: Aminolevulinic Acid (ALA); Device: BLU-U	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Pharmacokinetic Study of Levulan Kerastick (Aminolevulinic Acid HCl) for Topical Solution, 20% Under Maximal Use Conditions
• Study Start Date: February 2016
• Actual Primary Completion Date: May 2016
• Actual Study Completion Date: July 2016

Arms and Interventions

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 Name: Levulan Kerastick; Device: BLU-U; 10 J/cm2 of 417 nm blue light delivered at 10 mW/cm2; Other Name: Blue Light Photodynamic Therapy (PDT)

Outcome Measures

Primary Outcome Measures :

1. Maximum Baseline Corrected Plasma Concentration (Cmax) for ALA [ Time Frame: 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.
2. Time at Which Cmax is Attained (Tmax) for ALA [ Time Frame: 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.
3. AUCt [ Time Frame: 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
4. The Terminal Exponential Half-life (T1/2,z) for ALA [ Time Frame: 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.
5. Maximum Baseline Corrected Plasma Concentration (Cmax) for PpIX [ Time Frame: 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.
6. Time at Which Cmax is Attained (Tmax) for PpIX [ Time Frame: 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.
7. AUCBL for PpIX [ Time Frame: 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.
8. AUCt for PpIX [ Time Frame: 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.
9. AUCt/AUCBL for PpIX [ Time Frame: 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 :

1. Hyperpigmentation [ Time Frame: Baseline ]
   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
2. Hyperpigmentation [ Time Frame: 24 hours after 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
3. Hyperpigmentation [ Time Frame: 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
4. Hypopigmentation [ Time Frame: Baseline ]
   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
5. Hypopigmentation [ Time Frame: 24 hours after 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
6. Hypopigmentation [ Time Frame: 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
7. Erythema [ Time Frame: Baseline ]
   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
8. Erythema [ Time Frame: 5 Minutes after PDT ]
   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
9. Erythema [ Time Frame: 24 hours after PDT ]
   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
10. Erythema [ Time Frame: 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
11. Edema [ Time Frame: Baseline ]
    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
12. Edema [ Time Frame: 5 Minutes after 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
13. Edema [ Time Frame: 24 hours after 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
14. Edema [ Time Frame: 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
15. Stinging/Burning [ Time Frame: Baseline ]
    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
16. Stinging/Burning [ Time Frame: Intraprocedure ]
    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
17. Stinging/Burning [ Time Frame: 5 Minutes after photodynamic therapy ]
    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
18. Stinging/Burning [ Time Frame: 24 hours after 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
19. Stinging/Burning [ Time Frame: 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
20. Scaling and Dryness [ Time Frame: Baseline ]
    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
21. Scaling and Dryness at Visit 4 [ Time Frame: 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
22. Scaling and Dryness [ Time Frame: 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
23. OOZING/VESICULATION/CRUSTING [ Time Frame: Baseline ]
    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. OOZING/VESICULATION/CRUSTING [ Time Frame: 24 hours after 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
25. OOZING/VESICULATION/CRUSTING [ Time Frame: 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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Texas

DermResearch, Inc.

Austin, Texas, United States, 78759

J&J Studies, Inc

College Station, Texas, United States, 77845

Sponsors and Collaborators

DUSA Pharmaceuticals, Inc.

Investigators

• Study Director: Stuart Marcus, MD, PhD; DUSA Pharmaceuticals, Inc.

More Information

• Responsible Party: DUSA Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02628236
• Other Study ID Numbers: CP0113
• First Posted: December 11, 2015
• Results First Posted: September 18, 2017
• Last Update Posted: September 18, 2017
• Last Verified: September 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by DUSA Pharmaceuticals, Inc.:

Actinic keratosis

Additional relevant MeSH terms:

Keratosis, Actinic; Keratosis; Skin Diseases; Precancerous Conditions; Neoplasms; Aminolevulinic Acid; Photosensitizing Agents; Dermatologic Agents