MUSE Study of Levulan Kerastick

Keratosis, Actinic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02281136
• Other study ID #: CP0110
• Status: Completed
• Phase: Phase 2
• First received: October 30, 2014
• Last updated: December 14, 2015
• Start date: December 2014
• Est. completion date: April 2015

Study information

• Verified date: December 2015
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Keratosis
• Keratosis, Actinic

Intervention

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

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

Locations

Country	Name	City	State
United States	DermResearch, Inc.	Austin	Texas
United States	Shideler Clinical Research Center	Carmel	Indiana
United States	Therapeutics Clinical Research	San Diego	California

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	Maximum observed plasma concentration (Cmax) for ALA	Maximum observed plasma concentration (Cmax) for ALA over the 24 hour sampling time period based on actual values measured. Blood samples will 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	No
Primary	Time at which Cmax is attained (Tmax) for ALA	Time at which Cmax is attained (Tmax) 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	No
Primary	Area under the plasma concentration versus time curve from time zero to time tlast (time of last observed quantifiable concentration; AUC0-tlast) and AUC0-8 (if T1/2,z can be estimated) for ALA.	The area under the plasma concentration-time curve (AUC0-tlast) from time zero to the time of the last observed quantifiable plasma sample (tlast) will be calculated by the linear trapezoidal rule. The AUC from tlast to time infinity (AUCtlast-inf) will be calculated as the observed plasma concentration at tlast divided by the absolute value of slope (if t1/2,z can be determined). The total AUC from time zero to infinity (AUC0-inf) will be calculated as the sum of AUC0-tlast and AUCtlast-inf	1 day	No
Primary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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 after PDT	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	Scaling and Dryness at Visit 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	24 hours after PDT	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes