U0289-401: Eight Week, Split-face, Study to Determine and Compare the Efficacy and Tolerability of MAXCLARITY™ II to PROACTIV™

Study Overview
=================
Brief Summary
-----------------
One of the main success factors in acne therapy is user compliance with treatment, product cost, availability and ease of use. Poor compliance may translate into decreased efficacy (either not improving symptoms well enough or not improving symptoms fast enough), tolerability issues or adverse effects (eg, erythema, dryness, or peeling of the skin), a lack of understanding of the instructions for use, or product cost/availability. Whatever the reason, poor compliance translates to decreased efficacy and increased frustration on the part of the user. The current study will evaluate and compare the efficacy and tolerability of 2 over-the-counter, topical benzoyl peroxide (BPO) product lines in subjects with acne: MAXCLARITY II (2.5% BPO) Foam Cleanser and Foam Treatment and (0.5% Salicylic Acid) Toner Foam compared with PROACTIV (2.5% BPO) Renewing Cleanser and Repairing Lotion and Revitalizing Toner.

Detailed Description
-----------------
Acne vulgaris is an extremely common dermatological disease that is found typically in adolescence and young adulthood. Acne vulgaris manifests with open and closed comedones (blackheads and whiteheads), papules, pustules, nodules, and cysts on the face, neck, and trunk. Scarring can occur, particularly if the lesions are inflamed and deep, even in the absence of external manipulation (eg, picking and squeezing) of the skin. Acne vulgaris can be treated with a variety of agents that are selected to address the pathogenic factors assumed to be responsible for the type and degree of manifested acne lesions. Monotherapy and combination therapy regimens are both useful. Topical agents are generally used as first-line therapy and include retinoids, antibiotic preparations (eg, erythromycin and clindamycin), benzoyl peroxide (BPO), alpha and beta hydroxy acids (eg, glycolic and salicylic acid preparations), and azelaic acid. Systemic therapies are initiated in patients with moderate to severe inflammatory acne that does not respond to topical therapy. Benzoyl peroxide has antimicrobial and anti inflammatory properties and is often considered an important component of acne treatment. Benzoyl peroxide is frequently the first product that adolescents will use for acne because it can be purchased without a prescription in several different concentrations and formulations. One of the main success factors in acne therapy is user compliance with treatment, product cost, availability and ease of use. Poor compliance may translate into decreased efficacy (either not improving symptoms well enough or not improving symptoms fast enough), tolerability issues or adverse effects (eg, erythema, dryness, or peeling of the skin), a lack of understanding of the instructions for use, or product cost/availability. Whatever the reason, poor compliance translates to decreased efficacy and increased frustration on the part of the user. The current study will evaluate and compare the efficacy and tolerability of 2 common, over-the-counter, topical benzoyl peroxide (BPO) product lines in subjects with acne: MAXCLARITY II (2.5% BPO) Foam Cleanser and Foam Treatment and (0.5% Salicylic Acid) Toner Foam compared with PROACTIV(2.5% BPO) Renewing Cleanser and Repairing Lotion and Revitalizing Toner. This is a randomized, 2 center, evaluator-blinded, split-face efficacy and tolerability study of MAXCLARITYII and PROACTIV, 2 over-the-counter, topical benzoyl peroxide product lines, in subjects with acne. Approximately 40 subjects, aged from 16 to 29 years, inclusive, with mild facial acne vulgaris are expected to participate in the study. No more than 50% of the subjects at each site can be enrolled under the age of 20. An expert grader (blinded evaluator) will complete counts of inflamed lesions (papules/pustules) and noninflamed lesions (open/closed comedones), the Investigator's Static Global Assessment (ISGA), and an assessment of tolerability of each side of the face at each study visit. Subjects will assess tolerability on each side of the face at each study visit and will complete a product acceptability and preference questionnaire at the end of the study. The study duration will be 8 weeks (56 days) with visits at baseline (day 1), week 1m week 2, week 4 and week 8. Only the expert grader (evaluator) will be blinded to the study product assignments; subjects and study nurses/coordinator will not be blinded.

Official Title
-----------------
U0289-401: An Evaluator Blinded, 8 Week, Split-Face Study to Evaluate and Compare the Efficacy and Tolerability of MAXCLARITY II and PROACTIV in Subjects With Acne

Conditions
-----------------
Acne Vulgaris

Intervention / Treatment
-----------------
* Other: MAXCLARITY II (2.5% BPO) Foam Cleanser
* Other: MAXCLARITY II (2.5% BPO) Foam Treatment
* Other: MAXCLARITY II (0.5% Salicylic Acid) Toner Foam
* Other: PROACTIV (2.5% BPO) Renewing Cleanser
* Other: PROACTIV (2.5% BPO) Repairing Lotion
* Other: PROACTIV (2.5% BPO) Revitalizing Toner


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Capable of understanding and willing to provide signed and dated written voluntary informed consent (and any local or national authorization requirements) before any protocol specific procedures are performed. Male or female aged from 16 to 29 years, inclusive, at time of consent. No more than 50% of the subjects at each site can be enrolled under the age of 20. Mild facial acne vulgaris, characterized by at least 12 facial inflammatory lesions (papules and pustules) and/or noninflammatory lesions (open and closed comedones) on the face. Able to complete the study and to comply with study instructions. Sexually active females of childbearing potential participating in the study must agree to use a medically acceptable method of contraception while receiving protocol-assigned product. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant; including perimenopausal women who are less than 2 years from their last menses. Acceptable contraceptive methods include the following: Hormonal contraception, including oral, injectable, or implantable methods started at least 2 months prior to screening. If hormonal contraception was started less than 2 months prior to screening, then a form of nonhormonal contraception should be added until the third continuous month of hormonal contraception has been completed. Two forms of reliable nonhormonal contraception, to include the use of either an intrauterine device plus a reliable barrier method or 2 reliable barrier methods. Reliable barrier methods include condoms or diaphragms. A cervical cap is also a reliable barrier method, provided that the female subject has never given birth naturally. The combined use of a condom and spermicide constitute 2 forms of acceptable nonhormonal contraception, provided that they are both used properly. The use of spermicide alone and the improper use of condoms are inferior methods of contraception. Subjects with surgical sterilization, including tubal sterilization or partner's vasectomy, must use a form of nonhormonal contraception. A barrier method or sterilization plus spermatocide is acceptable. Women who are not currently sexually active must agree to use a medically accepted method of contraception should she become sexually active while participating in the study. Exclusion Criteria: Female who is pregnant, trying to become pregnant, or breast feeding. Has active or chronic skin allergies. Has a history of acute or chronic disease that might interfere with or increase the risk of study participation. Had skin cancer treatment in preceding 12 months. Has damaged skin on facial areas (eg, sunburn, tattoo, or scar) Had any medical procedure (eg, laser resurfacing, chemical peel, or plastic surgery) on facial areas in preceding 12 months. Had any cosmetic procedure (eg, microdermabrasion) on facial areas within 8 weeks of the baseline visit. Has any dermatological disorder that in the opinion of the investigator may interfere with the accurate evaluation of the subject's facial appearance. Received any investigational drug or procedure within 28 days of the baseline visit or is scheduled to receive an investigational drug (other than the study products) or procedure during the study. Currently using any medication that in the opinion of the investigator may affect the evaluation of the study products or place the subject at undue risk (including but not limited to asthma medications, oral steroids, rifampin, anticonvulsants, and St John's wart). Has a history of known or suspected intolerance to any of the ingredients of the study products (ie, benzoyl peroxide). Considered unable or unlikely to attend the necessary visits. Live in the same household as currently enrolled subjects. Employee of the investigator, a contract research organization, or Stiefel Laboratories who is involved in the study, or an immediate family member (partner, offspring, parents, siblings or sibling's offspring) of an employee involved in the study.

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 29 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MAXCLARITY II<br>MaxClarity II (2.5% BPO) Foam Cleanser and Foam Treatment and (0.5% Salicylic Acid) Toner Foam. Available over the counter. Each subject applies both arms (MaxClarity II and Proactiv) simultaneously for the entire duration of the study (8 weeks), each arm to be applied to one side of the face only (split-face study) according to randomization. | Other: MAXCLARITY II (2.5% BPO) Foam Cleanser<br>* Available over the counter.<br>Other: MAXCLARITY II (2.5% BPO) Foam Treatment<br>* Available over the counter.<br>Other: MAXCLARITY II (0.5% Salicylic Acid) Toner Foam<br>* Available over the counter.<br>|
| Active Comparator: PROACTIV<br>Proactiv (2.5% BPO) Renewing Cleanser and Repairing Lotion and Revitalizing Toner. Available over the counter. Each subject applies both arms (MaxClarity II and Proactiv) simultaneously for the entire duration of the study (8 weeks), each arm to be applied to one side of the face only (split-face study) according to randomization. | Other: PROACTIV (2.5% BPO) Renewing Cleanser<br>* Available over the counter.<br>Other: PROACTIV (2.5% BPO) Repairing Lotion<br>* Available over the counter.<br>Other: PROACTIV (2.5% BPO) Revitalizing Toner<br>* Available over the counter.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change in Inflammatory Lesion (IL), Non-inflammatory Lesion (NIL), and Total Lesion (TL) Counts From Baseline (BL) (Day 1) to Week (Wk) 8. | This was an efficacy variable. An expert grader evaluated each side of the face (included forehead, cheeks and chin), the left and the right side, for IL (presence of papules and pustules), NIL (presence of open and closed comedones) and the TLs. The mouth, nose, periocular area, nasogenian, and superior and inferior eyelids were excluded. The evaluator was also blinded. BL was defined as Day 1. The percent change was calculated as the value at Wk 8 minus the value at BL. | BL (Day 1) and Wk 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change in TL Count From BL (Day 1) to Wks 1, 2 and 4 | This was an efficacy variable. An expert grader (blinded) evaluated the left and the right side of the face extending from the hairline to the mandible (included forehead, cheeks and chin). The evaluator assessed the total lesions by the sum of both inflammatory and non-inflammatory lesions on each side (left side and right side). The mouth, nose, periocular area, nasogenian, and superior and inferior eyelids were excluded. BL was defined as Day 1. The percent change was calculated as the percent value (count of total lesions) at each individual visit (percent value at Wks 1, 2 and 4) minus the value at baseline respectively. | BL (Day 1) to Wks 1, 2 and 4 | 
| Mean Percent Change in IL Count From BL (Day 1) to Wks 1, 2 and 4 | This was an efficacy variable. An expert grader (blinded) evaluated the left and the right side of the face extending from the hairline to the mandible (included forehead, cheeks and chin). The evaluator assessed the IL by counting the number of papules and pustules. The mouth, nose, periocular area, nasogenian, and superior and inferior eyelids were excluded. BL was defined as Day 1. The percent change was calculated as the percent value (count of IL) at each individual visit (percent value at wk 1, 2 and 4) minus the value at BL respectively. | BL (Day1) to Wks 1, 2 and 4 | 
| Mean Percent Change in NIL Count From BL (Day 1) to Wks 1, 2 and 4 | This was an efficacy variable. An expert grader (blinded) evaluated the left and the right side of the face extending from the hairline to the mandible (included forehead, cheeks and chin). The evaluator assessed the NIL by the presence of open and closed comedones. The mouth, nose, periocular area, nasogenian, and superior and inferior eyelids were excluded. BL was defined as Day 1. The percent change was calculated as the percent value (count of NIL) at each individual visit (percent value at Wk 1, 2 and 4) minus the value at BL respectively. | BL (Day 1) to Wks 1, 2 and 4 | 
| Mean Change in Each of the Participant Assessments of Tolerability-Scaling | This was a tolerability variable, where the participants were instructed to individually assess the right and the left side of the face to indicate the severity that they had experienced during the time period from their last visit for scaling. The area on the face was assessed excluding nose, nasogenian, and superior and inferior eyelids. The assessment of the scaling was graded on 0 to 5 scale based on severity by the participant; 0=None, 1=Very minimal, 2=mild, 3= moderate, 4=severe, and 5= Very severe. Thus higher score indicated more severity. BL was defined as Day 1. The mean change was calculated as value at each individual visit (Wks 1,2,4 and 8) minus the value at BL respectively. | BL (Day 1) to Wks 1, 2, 4 and 8 | 
| Mean Change in Investigator's Static Global Assessment (ISGA) From BL (Day 1) to Wks 1, 2, 4 and 8. | The evaluator (blinded) evaluated the acne severity of the participants' face using the ISGA scale ranging from 0 to 5. The grading was 0= Clear, skin with no IL or NILs; 1= Almost clear, rare NILs with no more than one small IL ; 2= Mild, some NILs with no more than few ILs (papules/pustules only, no nodular lesions); 3= Moderate Upto many NILs and may have some ILs but no more than one small nodular lesion ; 4= Severe, Upto many NILs and ILs but no more than a few nodular lesions; 5= Very severe, many NILS and ILs more than a few nodular lesions, may have cystic lesions. Thus higher score indicated severity of the disease. BL was defined as Day 1. The mean change was calculated as value at each visit (Wks 1,2,4 and 8) minus the value at BL respectively. | BL (Day 1) to Wks 1, 2, 4 and 8 | 
| Mean Change in Each of the Evaluator Tolerability Assessments-Erythema | This was a tolerability variable. The expert grader (blinded evaluator) assessed each left and right side of the face individually at each study visit. The areas on the face excluding nose, nasogenian, and superior and inferior eyelids were evaluated. The evaluator conducting the assessment for the participant remained blinded for the treatment assigned. Erythema is condition characterized by redness or rash on the skin. The assessment of the erythema was graded on 0 to 5 scale based on severity by the evaluator. 0=None, 1=Very minimal, 2=mild, 3= moderate, 4=severe, and 5= Very severe. Thus higher score indicated severity of the disease. BL was defined as Day 1. The mean change was calculated as value at each individual visit (wk 1,2,4 and 8) minus the value at BL respectively. The change from BL was '0' for Wk 4 and Wk 8, and hence statistical analysis was not done. | BL (Day 1) to Wks 1, 2, 4 and 8 | 
| Mean Change in Each of the Evaluator Tolerability Assessments-Dryness | This was a tolerability variable. The expert grader (blinded evaluator) assessed each left and right side of the face individually at each study visit. The areas on the face excluding nose, nasogenian, and superior and inferior eyelids were evaluated. The evaluator conducting the assessment for the participant remained blinded for the treatment assigned. The assessment of the dryness was graded on 0 to 5 scale based on severity by the evaluator. 0=None, 1=Very minimal, 2=mild, 3= moderate, 4=severe, and 5= Very severe. Thus higher score indicated more severity. BL was defined as Day 1. The mean change was calculated as value at each individual visit (Wk 1,2,4 and 8) minus the value at baseline respectively. The change from BL was '0' for Wk 2, Wk 4, and Wk 8 and hence statistical analysis was not done. | BL (Day 1) to Wks 1, 2, 4 and 8 | 
| Mean Change in Each of the Evaluator Tolerability Assessments-Peeling | This was a tolerability variable. The expert grader (blinded evaluator) assessed each left and right side of the face individually at each study visit. The areas on the face excluding nose, nasogenian, and superior and inferior eyelids were evaluated. The evaluator conducting the assessment for the participant remained blinded for the treatment assigned. The assessment of the peeling was graded on 0 to 5 scale based on severity by the evaluator. 0=None, 1=Very minimal, 2=mild, 3= moderate, 4=severe, and 5= Very severe. Thus higher score indicated more severity. BL was defined as Day 1. The mean change was calculated as value at each individual visit (Wk 1,2,4 and 8) minus the value at BL respectively. The change from BL was '0' for Wk (1, 4 and 8) and hence statistical analysis was not done. | BL (Day 1) to Wks 1, 2, 4 and 8 | 
| Mean Change in Each of the Participant Tolerability Assessments-Redness | This was a tolerability variable, where the participants were instructed to individually assess the right and the left side of the face to indicate the severity that they had experienced during the time period from their last visit for redness. The area on the face was assessed excluding the excluding nose, nasogenian, and superior and inferior eyelids. The assessment of the redness was graded on 0 to 5 scale based on severity by the participant. 0=None, 1=Very minimal, 2=mild, 3= moderate, 4=severe, and 5= Very severe. Thus higher score indicated more severity. BL was defined as Day 1. The mean change was calculated as value at each individual visit (Wks 1,2,4 and 8) minus the value at BL respectively. | BL (Day 1) to Wks 1, 2, 4 and 8 | 
| Mean Change in Each of the Participant Assessments of Tolerability-Dryness | This was a tolerability variable, where the participants were instructed to individually assess the right and the left side of the face to indicate the severity that they had experienced during the time period from their last visit for dryness. The area on the face was assessed excluding the excluding nose, nasogenian, and superior and inferior eyelids. The assessment of the dryness was graded on 0 to 5 scale based on severity by the participant. 0=None, 1=Very minimal, 2=mild, 3= moderate, 4=severe, and 5= Very severe. Thus higher score indicated severity of the disease. BL was defined as Day 1. The mean change was calculated as value at each individual visit (Wks 1,2,4 and 8) minus the value at BL respectively. | BL (Day 1) to Wks 1, 2, 4 and 8 | 
| Mean Change in Each of the Participant Assessments of Tolerability-Burning | This was a tolerability variable, where the participants were instructed to individually assess the right and the left side of the face to indicate the severity that they had experienced during the time period from their last visit for burning. The area on the face was assessed excluding nose, nasogenian, and superior and inferior eyelids. The assessment of the burning was graded on 0 to 5 scale based on severity by the participant; 0=None, 1=Very minimal, 2=mild, 3= moderate, 4=severe, and 5= Very severe. Thus higher score indicated more severity. BL was defined as Day 1. The mean change was calculated as value at each individual visit (Wks 1, 2, 4 and 8) minus the value at BL respectively. | BL (Day 1) to Wks 1,2, 4 and 8 | 
| Mean Change in Each of the Participant Assessments of Tolerability-Itching | This was a tolerability variable, where the participants were instructed to individually assess the right and the left side of the face to indicate the severity that they had experienced during the time period from their last visit for itching. The area on the face was assessed excluding nose, nasogenian, and superior and inferior eyelids. The assessment of the itching was graded on 0 to 5 scale based on severity by the participant; 0=None, 1=Very minimal, 2=mild, 3= moderate, 4=severe, and 5= Very severe. Thus higher score indicated more severity. BL was defined as Day 1. The mean change was calculated as value at each individual visit (Wks 1,2,4 and 8) minus the value at BL respectively. | BL (Day 1) to Wks 1, 2, 4 and 8 |