Clinical trial NCT03168321
Conditions: Acne Vulgaris
Sponsor: Bausch Health Americas, Inc.
Start date: 2017-06-29; Completion date: 2018-06-07
Enrollment: 813 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a multicenter, randomized, double-blind, vehicle-controlled, 12-week study designed to assess the safety, efficacy, and tolerability of IDP-123 Lotion in comparison with IDP-123 Vehicle Lotion.

Detailed description:
This is a multi-center, randomized, double-blind, vehicle-controlled, 12-week study designed to assess the safety, efficacy, and tolerability of IDP-123 Lotion and IDP-123 Vehicle Lotion. To be eligible for the study subjects must be at least 9 years of age and have a clinical diagnosis of moderate to severe acne.

Arms: arm 1: Tazarotene 0.045% Lotion arm 2: Vehicle Lotion
Interventions: intervention 1: IDP-123 Lotion intervention 2: IDP-123 Vehicle Lotion
Intervention descriptions: intervention 1: Tazarotene 0.045% Lotion intervention 2: Vehicle Lotion

Protocol documents:
Prot_SAP_000.pdf: 
CLINICAL STUDY PROTOCOL 
 
IDP-123 
 
Protocol V01-123A-301 
 
A Phase 3, Multi-Center, Randomized, Double-Blind, Vehicle-
Controlled, 2 Arm, Parallel Group Study Comparing the Safety and 
Efficacy of IDP-123 Lotion and IDP-123 Vehicle Lotion in the 
Treatment of Acne Vulgaris 
 
 
Development Phase:  
3 
 
Study Design: 
Multi-center, randomized, double-blind, vehicle-controlled 
efficacy and safety study 
 
Date: 
24 August 2017 (Amendment 1) 
27 April 2017 (Original) 
 
Sponsor:  
Dow Pharmaceutical Sciences, a Division of Valeant 
Pharmaceuticals North America, LLC 
 
 
 
 
 
 
 
1330 Redwood Way, Suite C 
 
 
 
 
 
 
 
Petaluma, CA 94954 
 
 
 
 
 
 
 
707-793-2600 
 
 
 
CONFIDENTIAL 
Nothing herein is to be disclosed without prior approval of the Sponsor. 
 




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Personnel Responsible for Conducting the Study 
 
A Phase 3, Multi-Center, Randomized, Double-Blind, Vehicle-Controlled, 2 Arm, 
Parallel Group Study Comparing the Safety and Efficacy of IDP-123 Lotion and IDP-
123 Vehicle Lotion in the Treatment of Acne Vulgaris 
 
Contract Research Organization / Medical Monitor  
Cu-Tech, LLC 
333 US Highway 46W 
Mountain Lakes, NJ 
07046 
 
 
 
Cu-Tech Office Phone: (973) 331-1620 
 
 
 


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Principal Investigator Protocol Agreement Page 
I agree: 
• To assume responsibility for the proper conduct of this clinical study at this site and to 
conduct the study in compliance with this protocol, any future amendments, and with 
any other study conduct procedures provided by the sponsor. 
• That I am aware of, and will comply with, the internationally recognized code of Good 
Clinical Practices (GCP) and all other applicable regulatory requirements to obtain 
written and dated approval from the Institutional Review Board (IRB) or Independent 
Ethics Committee (IEC) for the study protocol, written informed consent, consent form 
updates, subject-recruitment procedures (e.g., advertisements), and any other written 
information to be provided to the subjects, before initiating this clinical study. 
• Not to implement any changes to, or deviations from the protocol without prior 
agreement from the sponsor and review and documented approval from the IRB/IEC, 
except to eliminate an immediate hazard to the study subjects, or when change(s) 
involves only logistical or administrative aspects of the clinical study. 
• To permit direct monitoring and auditing by the sponsor or sponsor’s representatives 
and inspection by the appropriate regulatory authority(ies). 
• That I am thoroughly familiar with the appropriate use of the investigational 
products(s), as described in this protocol, and any other information provided by the 
sponsor or designee, including, but not limited to, the current Investigator Brochure or 
equivalent document and approved product label (if applicable). 
• To provide sufficient time, and adequate numbers of qualified staff and facilities for the 
foreseen duration of the clinical study to conduct the study properly, ethically, and 
safely. 
• To ensure that all persons assisting in this study are adequately informed about the 
protocol, investigational product(s), and their clinical study-related duties and 
functions. 
 
 
 
 
Principal Investigator (print name) 
 
 
 
 
Principal Investigator (signature) 
 
Date 
 


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2 Synopsis 
Name of Sponsor/Company: Dow Pharmaceutical Sciences, a division of Valeant Pharmaceuticals North 
America, LLC 
Name of Investigational Product: IDP-123 Lotion 
Name of Active Ingredients: tazarotene 0.045% lotion 
Title of Study: A Phase 3, Multi-Center, Randomized, Double-Blind, Vehicle-Controlled, 2 Arm, Parallel 
Group Study Comparing the Safety and Efficacy of IDP-123 Lotion and IDP-123 Vehicle Lotion in the 
Treatment of Acne Vulgaris 
Number of clinical centers: Multicenter, approximately [32-50 ] investigational centers in North 
America  
Objective:  
The primary objective of this study is to compare the safety, efficacy, and tolerability of IDP-123 Lotion 
and IDP-123 Vehicle Lotion, in the treatment of subjects with moderate to severe acne vulgaris. 
Methodology:  
This is a multi-center, randomized, double-blind, vehicle-controlled, 12-week study designed to assess the 
safety, efficacy, and tolerability of IDP-123 Lotion and IDP-123Vehicle Lotion at Weeks 2, 4, 8, and 12. 
To be eligible for the study subjects must be at least 9 years of age and have a clinical diagnosis of 
moderate to severe acne (defined as an EGSS score of 3 or 4), presenting with 20-50 inflammatory facial 
lesions (papules, pustules, and nodules), 25-100 non-inflammatory facial lesions (open and closed 
comedones), and < 2 facial nodules. 
Approximately 800 subjects will be randomized to the following treatment groups: 
• 
400 Subjects to IDP-123 Lotion, once-daily application 
• 
400 Subjects to IDP-123 Vehicle Lotion, once-daily application 
All subjects will receive once daily, topically-applied treatment to the face for 12 weeks. Subject visits 
include Screening, Baseline, Week 2, Week 4, Week 8, and Week 12, at which safety and efficacy 
assessments will be conducted. Study drug will be dispensed to the Subjects at Baseline, Week 4 and 
Week 8. Subjects will be evaluated for drug usage compliance at each post-baseline study visit (Weeks 2, 
4, 8, and 12). Subjects will apply their treatments at home, once daily in the evening, as instructed by the 
study coordinator or designee at each investigational center (with the exception of study visit days, where 
study drug will be applied by the subject on-site during study visit).  
The investigator will assess the subject’s face at each study visit. Information on reported and observed 
AEs will be obtained at each visit. An abbreviated physical exam and vital signs measurement will be 
performed at Baseline and Week 12 (Final Visit) visits for all subjects. Blood samples will be collected 
from subjects at Baseline and Week 12, for CBC/Diff, serum chemistry, and serum pregnancy (for 
females of childbearing potential). For all pre-menses females and female subjects of childbearing 
potential (FOCBP), urine pregnancy testing will be performed at Screening, Baseline prior to 
randomization, and at Weeks 2, 4, 8, and 12. All subjects will be asked to complete the Acne-Specific 
Quality of Life (Acne-QoL) at Baseline and Week 12. In addition, at selected sites, standardized 
photography of the face will be performed at Baseline and Weeks 2, 4, 8, and 12. 
Number of subjects planned:  
Approximately 800 subjects with moderate to severe acne vulgaris will be enrolled and randomized in the 
study. Subjects will be randomized to the following treatment groups: 
• 
400 Subjects to IDP-123 Lotion, once-daily application 
• 
400 Subjects to IDP-123 Vehicle Lotion, once-daily application 
 


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Inclusion criteria:  
1. Male or female at least 9 years of age and older;  
2. Written and verbal informed consent must be obtained. Subjects less than age of consent must sign an 
assent for the study and a parent or a legal guardian must sign the informed consent (if subject reaches 
age of consent during the study they should be re-consented at the next study visit); 
3. Subject must have a score of 3 (moderate) or 4 (severe) on the Evaluator’s Global Severity assessment 
at the baseline visit; 
4. Subjects with facial acne inflammatory lesion (papules, pustules, and nodules) count no less than 20 
but no more than 50; 
5. Subjects with facial acne non-inflammatory lesion (open and closed comedones) count no less than 25 
but no more than 100; 
6. Subjects with two or fewer facial nodules;  
7. Women of childbearing potential and females who are pre-menses must be willing to practice 
effective contraception for the duration of the study. (Effective contraception is defined as stabilized 
on oral contraceptive for at least 3 months, IUD, condom with spermicidal, diaphragm with 
spermicidal, implant, Nuvaring, injection, transdermal patch or abstinence.). Females on birth control 
pills must have taken the same type pill for at least three months prior to entering the study and must 
not change type during the study. Those who have used birth control pills in the past must have 
discontinued usage at least three months prior to the start of the study. Women who use birth control 
for acne control only should be excluded. 
8. Pre-menses females and women of childbearing potential must have a negative urine pregnancy test at 
the screening and baseline visits; 
9. Subjects must be willing to comply with study instructions and return to the clinic for required visits. 
Subjects under the age of consent must be accompanied by the parent or legal guardian at the time of 
assent/consent signing; 
10. If a cleanser, moisturizer or sunscreen is needed during the study, Subjects must be willing to use only 
allowed cleansers, moisturizers, sunscreens, or moisturizer/sunscreen combination products (see 
Appendix 17.2). The subject must agree to use non-comedogenic products (including makeup and 
shaving products).  
Exclusion Criteria: 
1. Use of an investigational drug or device within 30 days of enrollment or participation in a research 
study concurrent with this study; 
2. Any dermatological conditions on the face that could interfere with clinical evaluations such as acne 
conglobata, acne fulminans, secondary acne, perioral dermatitis, clinically significant rosacea, gram-
negative folliculitis, dermatitis, eczema; 
3. Any underlying disease(s) or some other dermatological condition of the face that requires the use of 
interfering topical or systemic therapy or makes evaluations and lesion count inconclusive; 
4. Subjects with a facial beard or mustache that could interfere with the study assessments; 
5. Subjects with more than two (2) facial nodules; 
6. Evidence or history of cosmetic-related acne; 
7. Subject has a history of experiencing significant burning or stinging when applying any facial 
treatment (e.g., make-up, soap, masks, washes, sunscreens, etc) to their face; 
8. Female subjects who are pregnant, nursing mothers, planning a pregnancy during the course of the 
trial, or become pregnant during the study; 
9. Use of estrogens (e.g., Depogen, Depo-Testadiol, Gynogen, Valergen, etc.) for less than 12 weeks 
immediately preceding study entry; Subjects treated with estrogens 12 or more consecutive weeks 
immediately prior to study entry need not be excluded unless the Subject expects to change dose, drug 
or discontinue estrogen use during the study; 
10. If female, subject has a history of hirsutism, polycystic ovarian disease or clinically significant 
menstrual irregularities; 


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11. Treatment of any type of cancer within the last 6 months, with the exception of complete surgical 
excision of skin cancer outside the treatment area; 
12. Subject uses medications and/or vitamins during the study which are reported to exacerbate acne 
(azathioprine, haloperidol, Vitamin D, Vitamin B12, halogens such as iodides or bromides, lithium, 
systemic or mid-to super-high potency corticosteroids, phenytoin and phenobarbital); Multivitamins, 
including Vitamin A, at recommended daily doses, and Vitamin D at stable doses,  are acceptable; 
13. History of hypersensitivity or allergic reactions to any of the study preparations as described in the 
Investigator’s Brochure, including known sensitivities to any dosage form of tazarotene; 
14. Subjects taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, 
phenothiazines, sulfonamides). 
15. Concomitant use of potentially irritating over-the-counter products that contain ingredients such as 
benzoyl peroxide, alpha-hydroxy acid, salicylic acid, retinol or glycolic acids; 
16. Subjects that have not undergone the specified washout period(s) for the following topical 
preparations or physical treatments used on the face or subjects who require the concurrent use of any 
of the following in the treatment area: 
 
 
 
 
 
 
 
 
 
If the subject requires topical treatment for acne on areas other than the face (e.g., chest and/or back), 
the investigator may prescribe a product that does not contain tazarotene and must be noted in source 
documents and eCRF. 
17. Subjects that have not undergone the specified washout period(s) for the following systemic 
medications or subjects who require the concurrent use of any of the following systemic medications: 
- 
Corticosteroids (including intramuscular injections)  
       (inhaled corticosteroids allowed)                                                      4 weeks 
- 
Antibiotics                                                                                         4 weeks 
- 
Other systemic acne treatments  
    4 weeks 
- 
Systemic retinoids 
    6 months 
18. Subject intends to use a tanning booth or sunbathe during the study. 
19. Subjects who are unable to communicate or cooperate with the Investigator due to language problems, 
poor mental development, or impaired cerebral function. 
20. Subjects with any underlying disease that the Investigator deems uncontrolled, and poses a concern 
for the subject’s safety while participating in the study. 
- 
Topical astringents and abrasives (including comedone 
removal strips) on the face 
1 week 
- 
Non-allowed moisturizers or sunscreens on the face 
1 week 
- 
Antibiotics on the face 
2 weeks 
- 
Other topical anti-acne drugs on the face  
2 weeks 
- 
Soaps containing antimicrobials on the face  
2 weeks 
- 
Anti-inflammatory agents and corticosteroids on the face 
4 weeks 
- 
Retinoids, including retinol on the face  
4 weeks 
- 
Facial procedures, including chemical peel, 
microdermabrasion, light (PDT, LED) and laser therapy, and 
acne surgery  
4 weeks 
Investigational product, dosage and mode of administration:  
Investigational Product: IDP-123 (tazarotene 0.045%) Lotion, applied topically to the face, once daily for 
12 weeks.  
Comparator Product: 
IDP-123 Vehicle Lotion, applied topically to the face, once daily for 12 weeks. 
Duration of treatment:  
12 weeks for all subjects. 
Reference therapy, dosage and mode of administration:  
See comparator product above. 


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Criteria for evaluation: 
Co-Primary Efficacy: 
IDP-123 Lotion will be compared to IDP-123 Vehicle Lotion. 
Co-primary endpoints are:  
(1) Superiority in absolute change from Baseline to Week 12 in mean inflammatory lesion counts 
(2) Superiority in absolute change from Baseline to Week 12 in mean non-inflammatory lesion counts, 
and,  
(3) Percent of subjects who achieve at least a two-grade reduction from baseline and are Clear or Almost 
Clear at Week 12 in the Evaluator’s Global Severity Score. 
Secondary Efficacy: 
• 
Percent change in inflammatory lesion count from Baseline to Week 12  
• 
Percent change in non-inflammatory lesion count from Baseline to Week 12  
• 
Proportion of subjects who have at least a 2 grade reduction at Week 12 from Baseline in the 
Evaluator’s Global Severity Score 
• 
Percent change in inflammatory lesion count from Baseline to Week 8 
• 
Percent change in non-inflammatory lesion count from Baseline to Week 8 
• 
Percent change in inflammatory lesion count from Baseline to Week 4 
• 
Percent change in non-inflammatory lesion count from Baseline to Week 4 
 
Supportive Efficacy: 
• 
Percent change in inflammatory lesion count from Baseline to Week 2 
• 
Percent change in non-inflammatory lesion count from Baseline to Week 2 
• 
Proportion of subjects who have at least a 2 grade reduction at Week 8 from Baseline in the 
Evaluator’s Global Severity Score 
• 
Proportion of subjects who have at least a 2 grade reduction at Week 4 from Baseline in the 
Evaluator’s Global Severity Score 
• 
Proportion of subjects who have at least a 2 grade reduction at Week 2 from Baseline in the 
Evaluator’s Global Severity Score 


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Efficacy Measurements: 
Lesion Counts 
At each visit the Evaluator will count the total number of inflammatory lesions (papules, pustules, and 
nodules) on the subject’s face. Nodules will be counted separately but will be included in the total 
inflammatory lesion count. At baseline, eligible subjects may have no more than two nodules. Nodules 
will be included in the statistical analysis of inflammatory lesion counts. All inflammatory lesions will be 
counted at the same time rather than counting papules and pustules separately. The Evaluator will also 
count the total number of non-inflammatory lesions (open and closed comedones).  The same blinded 
evaluator should perform the lesion counts and EGSS evaluations at all visits from baseline to Week 12 
for the same subject. 
Inflammatory lesions are defined as follows: 
Papule – a small, solid elevation less than 5 mm in diameter. Most of the lesion is above the surface of the 
skin.  
Pustule – a small, circumscribed elevation less than 5 mm in diameter that contains yellow-white exudate. 
Nodule – a subcutaneous lesion greater than or equal to 5 mm in diameter 
Non-inflammatory lesions are defined as follows: 
Open comedones (black head) - a lesion in which the follicle opening is widely dilated with the contents 
protruding out onto the surface of the skin. 
Closed comedones (white head)– a lesion in which the follicle opening is closed, but the sebaceous gland 
is enlarged by the pressure of the sebum build up, which in turn causes the skin around the follicle to thin 
and become elevated with a white appearance.  
Evaluator’s Global Severity Score (EGSS) 
At each visit the severity will be determined based on evaluator-blinded evaluations of the signs and 
symptoms of acne vulgaris. Evaluations will be scored on a scale of 0-4, with 0 being clear and 4 being 
severe.  Please see the table below for complete definitions. 
Score 
Grade 
Description 
0 
Clear 
Normal, clear skin with no evidence of acne vulgaris 
1 
 
Almost clear 
Rare non-inflammatory lesions present, with rare non-inflamed papules (papules must 
be resolving and may be hyperpigmented, though not pink-red) 
2 
 
Mild 
Some non-inflammatory lesions are present, with few inflammatory lesions 
(papules/pustules only; no nodulo-cystic lesions) 
3 
 
Moderate 
Non-inflammatory lesions predominate, with multiple inflammatory lesions evident: 
several to many comedones and papules/pustules, and there may or may not be one 
nodulo-cystic lesion 
4 
 
Severe 
Inflammatory lesions are more apparent, many comedones and papules/pustules, there 
may or may not be up to 2 nodulo-cystic lesions 
Safety Assessments: 
Cutaneous safety and tolerability will be evaluated by tabulations of adverse events and Cutaneous Safety 
and Tolerability Evaluation scores (scaling, erythema, hypo/hyperpigmentation, itching, burning, and 
stinging) to be assessed at each study visit. Itching, burning and stinging (Cutaneous tolerability) will be 
reviewed with the subject at each study visit as an average over the period since the previous visit. 
Scaling, erythema and hypo/hyper-pigmentation (Cutaneous Safety) will be assessed by the evaluator at 
each visit. Cutaneous tolerability signs and symptoms that result in the subject requiring a concomitant 
therapy, interruption of treatment, or discontinuation from the study will be reported as an AE.  
 
At selected sites, standardized photography of the face will be performed. 


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Statistical methods: 
All statistical processing will be performed using SAS® version 9.3 or later unless otherwise stated.  
Statistical significance will be based on two-tailed tests of the null hypothesis resulting in p-values of 0.05 
or less. Tests of lesion count superiority will be based on an ANCOVA with factors of treatment and 
analysis center and the respective Baseline lesion count as a covariate or on ranked data submitted to an 
ANCOVA with factors of treatment and analysis center and the respective Baseline lesion count as a 
covariate. The co-primary analysis of the dichotomized EGSS will be based on logistic regression with 
factors of treatment group and analysis center. The primary method of handling missing efficacy data will 
be based on estimation using the method of Markov Chain Monte Carlo (MCMC) imputation.  
Additionally, a model-based multiple imputation process will be used as a sensitivity analysis to the 
MCMC imputation. Finally, the absolute change in lesion count will be analyzed using a repeated 
measures ANCOVA for lesion count data or a repeated measures logistic regression model (generalized 
estimating equations) for the dichotomized EGSS.     
Inflammatory and non-inflammatory lesion counts will be recorded for each Subject at Baseline and at 
Weeks 2, 4, 8, and 12. The absolute and percent change from Baseline in inflammatory and non-
inflammatory lesions will be derived for each Subject at Weeks 2, 4, 8, and 12.  
The EGSS will be recorded for each Subject. The EGSS will be dichotomized into “success” and “failure” 
with a Subject considered a success if the Evaluator’s Global Severity Score at Week 2, 4, 8, and 12 is at 
least 2 grades less than baseline and Clear or Almost Clear.  
Populations Analyzed: 
An intent-to-treat (ITT) analysis will be conducted on all study subjects. The ITT population will consist 
of all randomized subjects who were dispensed study medication. 
The safety population will be comprised of all randomized subjects who are presumed to have used the 
study medication at least once and who provide at least one post-baseline safety evaluation. A per-
protocol (PP) analysis will also be conducted. Subjects will be eligible for the PP analysis if they complete 
the 12-week evaluation without noteworthy study protocol violations (i.e., any Subject or investigator 
activity that could have possibly interfered with the therapeutic administration of the treatment or the 
precise evaluation of treatment efficacy). The PP population will include subjects in the safety population 
who do not meet any of the following criteria: 
• Failed any of the inclusion/exclusion criteria; 
• Have taken any interfering concomitant medications; 
• Did not attend the Week 12 visit; 
• Missed more than 1 post baseline study visit prior to Week 12  
• Have not been compliant with the dosing regimen (i.e., Subjects may not miss more than 
five consecutive days of dosing and must take 80-120% of expected doses. The number of 
expected doses will be determined for each subject based on the length of their 
participation in the study); 
• Out of visit window at the 12-week visit. 
Subjects that discontinue from the study due to an adverse event related to study treatment or documented 
lack of treatment effect will be included in the PP population. Prior to breaking the blind, other additional 
criteria may be added to the list to accommodate for unforeseen events that occurred during the conduct of 
the trial that result in noteworthy study protocol violations. 
Approximately 800 subjects with moderate or severe acne will be enrolled and randomized to the 
following treatment groups: 
• 
400 subjects to receive IDP-123 Lotion, once-daily application 
• 
400 subjects to receive IDP-123 Vehicle Lotion, once-daily application 
Subject demographic and baseline characteristics will be summarized by treatment group using descriptive 
statistics for the ITT, PP, and safety analysis sets. 


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Efficacy Evaluation: 
Primary efficacy analyses will be conducted on the ITT (primary) and PP (supportive) populations.   
Secondary and supportive analyses will be conducted on the ITT population.  
Primary: 
Co-primary efficacy analyses include the absolute change from baseline in inflammatory and in non-
inflammatory lesions, and the dichotomized Evaluator’s Global Severity Score.  The pre-specified time 
point will be Week 12. All of the testing relating to the analysis of inflammatory and non-inflammatory 
lesions will use the methods introduced in Section 12. 
Secondary:  
Secondary efficacy endpoints include percent change in inflammatory and non-inflammatory lesion 
counts from baseline to Weeks 12, 8 and 4 and also proportion of subjects with at least a two grade 
improvement in the Evaluator’s Global Severity Score from baseline to Week 12.  
Supportive: 
Additional supportive efficacy endpoints include percent change in inflammatory and non-inflammatory 
lesions counts from baseline at Week 2, as well as proportion of subjects with at least a two grade 
improvement in the Evaluator’s Global Severity Score from baseline at Weeks 2, 4, and 8. 
Safety Evaluation: 
All subjects who receive medication and provide at least one post-baseline safety evaluation will 
constitute the safety population. Safety will be evaluated by tabulations of adverse events (AEs), 
Cutaneous Tolerability Evaluations, vital signs/abbreviated physical exams, and safety labs.  
Cutaneous Safety Evaluation scores (erythema, scaling, and hypo/hyper-pigmentation) and Tolerability 
(itching, burning, and stinging) will be presented with descriptive statistics at Baseline and at Weeks 2, 4, 
8, and 12 for each treatment group. Frequencies and percentages for each outcome category will be 
included in these statistics. Mean values will be presented graphically by week and treatment group. 
Vital signs and an abbreviated physical exam, and safety labs will be conducted on all subjects at specified 
visits. For pre-menses females and females of child-bearing potential (FOCBP), urine pregnancy testing 
and serum pregnancy testing will occur at specified visits. Changes from baseline in safety laboratory 
values and vital sign measurements will be summarized with descriptive statistics for each treatment 
group at all applicable study visits. Shift tables will be presented for changes in safety laboratory values to 
summaries laboratory test results collected at Baseline and Week 12 Visits. Normal ranges established by 
the central laboratory will be used to determine the shifts. A listing of all out-of-range laboratory test 
results at any assessment time point will also be provided.  
Determination of clinical significance for all out-of-range laboratory values will be made by each 
investigator and included in the listing. In addition, a listing of all clinical significant laboratory test 
results will be provided.  
All previous concomitant medications will be classified based on terminology from the WHO Drug 
Dictionary. Previous therapies and concomitant medications data will be presented in the data listings. 
All adverse events occurring during the study will be recorded and classified on the basis of MedDRA 
terminology. Descriptions of AEs will include the date of onset, the date the AE ended, the severity of the 
AE, the relationship to study medication, the action taken regarding study medication usage, the action 
taken regarding to treat the AE, and the outcome. Adverse events will be summarized by treatment group 
and severity.  Each subject will be counted only once within a system organ class or a preferred term by 
using the adverse events with the highest severity within each category. 
Adverse events will be summarized by treatment group and relationship to study medication.  Each 
subject will be counted only once within a system organ class or a preferred term by using the adverse 
events with the greatest relationship within each category. 


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Comparisons among treatment groups will be made by tabulating the frequency of subjects with one or 
more AEs (classified into MedDRA terms) during the study.  The Fisher’s Exact test will be used to 
compare the proportion of subjects in each treatment group who report any adverse event at a significance 
level of 0.05.  The specific system organ classes and preferred terms analyzed will be those that are 
reported by at least one percent of the subjects in any treatment group. 
All information pertaining to AEs noted during the study will be listed by subject, detailing verbatim 
given by the investigator, preferred term, system organ class, start date, stop date, severity, actions taken, 
and drug relatedness. The AE onset will also be shown relative (in number of days) to the day of initial 
dose of the randomized study medication. 
Serious adverse events (SAEs) will be tabulated by subject within treatment groups. 
In addition, a list of subjects who discontinued from the study and a list of subjects who experienced 
SAEs will also be provided. 
Subject Self-Assessment 
Subjects will be asked to complete the Acne-Specific Quality of Life Questionnaire during the study.    
Inferential statistical analysis will not be performed on the questionnaire; the subjective responses will be 
compared between treatment groups for trends. 
 
 
 
This study will be performed in compliance with GCP including the archiving of essential study 
documents. This protocol follows guidelines outlined by the International Conference on Harmonization 
(ICH). All data furnished to the investigator and his/her staff, and all data obtained through this study, will 
be regarded as confidential and proprietary in nature and will not be disclosed to any third party, except 
for the United States Food and Drug Administration or other regulatory body, without written consent 
from the sponsor. 


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3 Table of Contents 
1 
TITLE PAGE ...........................................................................................................1 
2 
SYNOPSIS ...............................................................................................................5 
3 
TABLE OF CONTENTS .......................................................................................13 
4 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................17 
5 
INTRODUCTION .................................................................................................18 
6 
STUDY OBJECTIVES AND PURPOSE .............................................................19 
7 
INVESTIGATIONAL PLAN ................................................................................19 
7.1 
Overall Study Design and Plan: Description .............................................19 
8 
SELECTION AND WITHDRAWAL OF SUBJECTS .........................................22 
8.1 
Subject Inclusion Criteria ..........................................................................22 
8.2 
Subject Exclusion Criteria .........................................................................23 
8.3 
Subject Withdrawal Criteria ......................................................................24 
9 
TREATMENT PLAN ............................................................................................26 
9.1 
Methods of Assigning Subjects to Treatment Groups ...............................26 
9.2 
Randomization and Blinding .....................................................................26 
9.3 
Unblinding .................................................................................................27 
9.4 
Prior and Prohibited Concomitant Medication or Therapy........................27 
9.5 
Treatment Compliance ...............................................................................28 
9.6 
Protocol Deviations and Violations ...........................................................29 
10 
STUDY DRUG MATERIALS AND MANAGEMENT ......................................29 
10.1 
IDP-123 Lotion, and IDP-123 Vehicle Lotion ..........................................29 
10.1.1 Packaging and Labeling .................................................................30 
10.1.2 Storage, Handling, and Disposal of Study Drug ............................31 
10.1.3 Administration ...............................................................................31 
10.2 
Study Drug Accountability ........................................................................32 
11 
STUDY PROCEDURES AND EVALUATIONS ................................................33 
11.1 
Schedule of Evaluations and Procedures ...................................................33 
11.1.1 Visit 1: Screening Visit (Day -35 to Day 0) ..................................33 
11.1.2 Visit 2: Baseline Visit (Day 0) .......................................................34 
11.1.3 Visit 3: Week 2 (Day 14 ± 3 Days) Visit .......................................35 
11.1.4 Visit 4: Week 4 (Day 28 ± 3 Days) Visit .......................................36 
11.1.5 Visit 5: Week 8 (Day 56 ± 3 Days) Visit .......................................37 
11.1.6 Visit 6: Week 12 (Day 84 -3/+5 Days) Visit – End of 
Treatment/Study Visit ....................................................................38 
11.2 
Evaluation of Efficacy ...............................................................................39 


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11.2.1 Evaluator’s Global Severity Score (EGSS) ...................................39 
11.2.2 Lesion Counts ................................................................................39 
11.2.3 Other Assessments .........................................................................40 
11.3 
Evaluation of Safety ...................................................................................40 
11.3.1 Cutaneous Safety Evaluations ........................................................40 
11.3.2 Tolerability Evaluations .................................................................41 
11.3.3 Medical History and Abbreviated Physical Examination ..............42 
11.3.4 Laboratory Tests ............................................................................42 
11.3.5 Pregnancy Tests .............................................................................42 
11.4 
Adverse Events ..........................................................................................42 
11.4.1 Definition of Adverse Event ..........................................................42 
11.4.2 Documenting Adverse Experiences ...............................................43 
11.4.3 Serious Adverse Events .................................................................43 
11.4.4 Assessment of Severity ..................................................................44 
11.4.5 Assessment of Causality ................................................................44 
11.4.6 Reporting of Serious Adverse Events ............................................45 
11.4.7 Expedited Serious Adverse Event Reports ....................................46 
11.4.8 Pregnancy .......................................................................................46 
12 
STATISTICS .........................................................................................................47 
12.1 
Assessment of Efficacy ..............................................................................48 
12.1.1 Primary Efficacy ............................................................................48 
12.1.2 Secondary Efficacy ........................................................................48 
12.1.3 Supportive Efficacy .......................................................................48 
12.1.4 Test of Superiority for Lesion Count Variables .............................49 
12.1.5 Test of Superiority for EGSS .........................................................49 
12.1.6 Statistical Hypothesis Testing and Control of Multiplicity ...........49 
12.1.7 Descriptive Statistics ......................................................................51 
12.1.8 Pooling Analysis ............................................................................51 
12.1.9 Missing Efficacy Data Imputations ...............................................53 
12.1.10 Sensitivity Efficacy Analyses .......................................................55 
12.1.11 Subgroup Analyses .......................................................................56 
12.1.12 Subject Self-Assessments .............................................................56 
12.2 
Assessment of Safety .................................................................................56 
12.2.1 Adverse Events ..............................................................................56 
12.2.2 Safety Laboratory Tests .................................................................57 
12.2.3 Vital Sign Measurements ...............................................................57 
12.2.4 Concomitant Medications ..............................................................58 
12.3 
Subject Disposition ....................................................................................58 
12.4 
Demographics and Baseline Characteristics ..............................................58 


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12.5 
Protocol Deviations ....................................................................................58 
12.6 
Compliance ................................................................................................58 
12.7 
Interim Analyses ........................................................................................58 
12.8 
Additional Statistical Considerations .........................................................58 
12.8.1 Analysis Populations ......................................................................58 
12.8.2 Sample Size Determination............................................................59 
12.8.3 Handling of Missing Data ..............................................................60 
12.8.4 Multicenter Issues ..........................................................................60 
12.8.5 Multiplicity Issues ..........................................................................60 
12.8.6 Windowing Rules...........................................................................60 
13 
QUALITY CONTROL AND QUALITY ASSURANCE .....................................60 
13.1 
Study Monitoring .......................................................................................60 
13.2 
Audits and Inspections ...............................................................................61 
13.3 
Data Quality Assurance .............................................................................61 
14 
ETHICS AND ADMINISTRATIVE ISSUES ......................................................61 
14.1 
Ethical Conduct of the Study .....................................................................61 
14.2 
Ethics Review ............................................................................................62 
14.3 
Written Informed Consent .........................................................................62 
14.4 
Subject Data Protection..............................................................................63 
14.5 
Data Monitoring Committee ......................................................................63 
14.6 
Financial Disclosure...................................................................................63 
14.7 
Investigator Obligations .............................................................................63 
14.8 
Changes to the Protocol .............................................................................63 
14.9 
Confidentiality/Publication of the Study ...................................................63 
15 
DATA HANDLING AND RECORD KEEPING .................................................64 
15.1 
Inspection of Records ................................................................................64 
15.2 
Retention of Records..................................................................................65 
16 
REFERENCES ......................................................................................................66 
17 
APPENDICES .......................................................................................................67 
17.1 
Subject Instruction Sheet ...........................................................................67 
17.2 
Cleansers, Moisturizers and Sunscreen Use Guidelines ............................69 
17.3 
Acne-Specific Quality of Life Questionnaire (Acne-QoL) .......................70 
 
LIST OF TABLES 
Table 1. 
Study Design and Schedule of Assessments ..................................................21 


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Table 2. 
Drug Substances Identification……………………………………………..29 
Table 3. 
Test Product Identification………………………………………………….29 
Table 4. 
Evaluator’s Global Severity Score………………………………………….39 
 


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4 List of Abbreviations and Definitions of Terms 
Abbreviation or Specialist Term 
Definition or Explanation 
AE 
Adverse event 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
cGCP 
Current Good Clinical Practice 
eCRF 
Electronic Case Report Form 
EGSS 
Evaluator’s Global Severity Score 
ET 
Early termination 
FDA 
United States Food and Drug Administration 
FOCBP 
Female of Childbearing Potential 
g 
Gram 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat  
IWRS 
Interactive Web Response System 
LED 
Light Emitting Diode 
LOCF 
Last observation carried forward 
MedDRA 
Medical Dictionary for Regulatory Affairs 
mL 
Milliliter 
OTC 
Over-the-counter 
PDT 
Photodynamic Therapy 
PP 
Per protocol 
QoL 
Quality of Life 
SAE 
Serious adverse event 
UPT 
Urine Pregnancy Test 
WHO 
World Health Organization 
 
In this protocol, “sponsor duties” refer to responsibilities that will be performed by the 
sponsor, the sponsor’s designee, or the sponsor’s designated contract research organization. 
In this protocol, “investigator” refers to the principal investigator or his/her designee, who is 
responsible for performing the study procedures and assessments. 


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5 Introduction 
Acne is a very common disorder of sebaceous follicles that usually begins at the time of the 
sharp increase in androgen production occurring in adolescence [1]. The disease is most 
prevalent amongst teenagers, but it does occur later in life, particularly in the third and fourth 
decade. The pathogenesis is complex and involves an androgen-stimulated increase in sebum 
production, associated with follicular hyperkeratinization and obstruction of the sebaceous 
follicles. This results in abnormal desquamation of the follicular epithelium, and is associated 
with bacterial proliferation (especially Propionibacterium acnes (P. acnes)) and chronic 
inflammation associated with acne. These changes in acne subjects result in enlarged 
sebaceous glands; obstruction of the follicular canal with associated sebum retention and 
distention of the follicle by tightly packed horny cells that lead to the formation clinical 
inflammatory lesions including superficial pustules such as comedones (popularly known as 
“blackheads” or “whiteheads”); and more deeply located papules, nodules and cysts [1]. The 
areas most affected by the disease include the pilosebaceous follicles of the head and upper 
trunk, where the sebaceous glands are particularly active [2]. 
Currently, therapeutic treatment of acne is directed against 3 principal pathogenic factors of 
the disease, including the bacterial colonization of follicles, the hypersecretion of the 
sebaceous gland, and intrafollicular hypercornification that induces follicular obstruction. 
Effective treatment directed against the colonization of bacteria (P. acnes) in follicles has 
made use of anti-infectives such as topical benzoyl peroxide (2.5%-10%), clindamycin, and 
erythromycin and systemic tetracyclines; however, known disadvantages to this treatment 
modality include irritation and limited use due to pathogen resistance [2-5]. Effective 
treatment directed towards inhibiting sebaceous gland activity has included oral 
corticosteroids, spironolactone, and isotretinoin in addition to anti-androgens 
(eg, cyproterone acetate). Known disadvantages to this treatment modality include being 
limited to use in females (anti-androgens), and limited to short term use for safety (oral 
corticosteroids). Finally, effective treatment directed against intrafollicular 
hypercornification has made use of retinoids such as oral isotretinoin and topical tretinoin or 
isotretinoin to regulate the intrafollicular keratinization process, inhibiting follicular 
hyperkeratinization and follicular obstruction [6]. In general, the known usefulness of oral 
retinoids (ie, oral isotretinoin) is limited by their side effects, which range from relatively 
minor effects (e.g., dryness of mucosa and skin, skin irritation, and skin scaling) to major 
toxicity syndromes (reversible hair loss, bone toxicity and teratogenicity) and may include 
varying degrees of symptoms associated with hypervitaminosis A syndrome [2, 7, 8]. 
Likewise, the efficacy of topical retinoids such as tretinoin or isotretinoin may be limited by 
the known side effects, which include significant erythema, dryness, peeling, scaling, and 
irritation [9].  
 


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Tazarotene is a retinoid prodrug that activates 3 members of the retinoid acid receptor (RAR) 
nuclear receptors (RARα, RARβ, and RARγ), which act to modify gene expression, subsequent 
protein synthesis, and epithelial cell growth and differentiation. Tazarotene shows a relative 
selectivity for RARβ, and RARγ. It has not been established, however, whether the clinical 
effects of tazarotene are mediated through activation of RARs, other mechanisms, or both. 
Although the mechanism of action for tazarotene in the treatment of acne is unknown, the drug’s 
antihyperproliferative, normalizing-of-differentiation, and anti-inflammatory effects may be 
related to the observed efficacy.  
IDP-123 is a lotion containing 0.045% tazarotene for the topical treatment of acne. This 
proposed product is the first lotion formulation developed for tazarotene and will be 
evaluated for safety and effectiveness in treating acne vulgaris. 
6 Study Objectives and Purpose  
The primary objective of this study is to evaluate the safety, efficacy, and tolerability of a 
once-daily topical application of IDP-123 Lotion compared to the IDP-123 Vehicle Lotion in 
subjects with moderate to severe acne vulgaris (a score of 3 or 4 [moderate to severe] on the 
Evaluator’s Global Severity Score (EGSS) scale). 
7 Investigational plan 
7.1 
Overall Study Design and Plan: Description 
This is a multicenter, randomized, double-blind, vehicle-controlled study designed to assess 
the safety, efficacy, and tolerability of IDP-123 Lotion in comparison with IDP-123 Vehicle 
Lotion. To be eligible for the study, subjects must be at least 9 years of age and older and 
have a clinical diagnosis of moderate to severe acne vulgaris (a score of 3 or 4 [moderate to 
severe] on the EGSS scale). 
Approximately 800 subjects will be enrolled into this study and randomized into one (1) of 
two (2) treatment groups: 
• 400 subjects in the IDP-123 Lotion, once-daily application group 
• 400 subjects in the IDP-123 Vehicle Lotion, once-daily application group 
Subjects will be enrolled at approximately 32-50 independent study centers. The duration of 
treatment will be 12 weeks. Subjects will be evaluated at Screening, Baseline and at 
subsequent follow-up visits (Weeks 2, 4, 8, and 12). 
An interactive web based response system (IWRS) will be employed to facilitate 
randomization of study subjects. Treatment assignments and study drug kit numbers will be 
generated centrally by the IWRS. At each clinical site, subject numbers will be assigned 
consecutively at the screening visit starting with 001. 


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The assigned study drug will be applied topically to the face once daily at home, in the 
evening, for 12 weeks (up to the evening prior to Week 12 visit) with the exception of study 
visit days (Baseline, Weeks 2, 4 and 8) where study drug will be applied (also by the subject) 
after the study visit is completed at the investigational center. The initial application will be 
applied at the investigational center as per instruction from the study coordinator or designee. 
The subjects will be instructed to avoid exposure to direct sunlight to prevent sunburn and 
should be instructed to use sunscreens of at least SPF 15 and wear protective clothing (e.g., 
hat). During post-baseline study visits (Weeks 2, 4, 8, and 12) the subjects will be asked to 
return their used tubes of study drug and will be dispensed new tubes of study drug (only at 
Weeks 4 and 8; Week 2 will have no new study drug dispensed, and Week 12 will be final 
visit). During the study, each subject will only be permitted to use approved non-medicated 
cleansers, moisturizers and sunscreens. 
Subjects will be asked to complete the Acne-Specific Quality of Life Questionnaire (Acne-
QoL, Appendix 17.3).  The Acne-QoL will be completed at baseline and Week 12.  
Inferential statistical analysis will not be performed on the questionnaire; the subjective 
responses will be compared between treatment groups for trends. 
The EGSS should be completed prior to the lesion counts. 
Information on reported and observed adverse events (AEs) will be obtained at each visit. An 
abbreviated physical examination and vital sign measurements will be performed at Baseline 
and Week 12 Visits (final visit) for all subjects. 
For all pre-menses females and female subjects of childbearing potential, urine pregnancy 
testing will be performed at Screening and confirmed at Baseline prior to randomization, and 
at Weeks 2, 4, 8 and 12. Serum pregnancy tests will also be conducted at Baseline and Week 
12 / early termination. 
Safety laboratory testing will be conducted at Baseline and Week 12 / early termination. 
Subjects who terminate study participation early will be asked to complete all Week 12 
assessments, as appropriate. Subjects who discontinue from the study during the treatment 
period will not be replaced. 
A “Re-screened” subject (e.g., subject that is rescreened beyond the allowed screening period 
window) will be considered a new subject and will need to be re-consented, receive a new 
screening number, and be entered in IWRS as a new subject. All screening assessments for 
re-screened subjects will need to be completed.


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Table 1. 
Study Design and Schedule of Assessments 
PROCEDURES 
VISIT 11 
Screening Visit 
Day -35 to 0 
VISIT 2 
Baseline 
Day 0 
VISIT 3 
Week 2 
(Day 14 ±3 days) 
VISIT 4 
Week 4 
(Day 28 ±3 days) 
VISIT 5 
Week 8 
(Day 56 ± 3 days) 
VISIT 65 
Week 12  
(Day 84 -3/+5 days) 
Informed consent/Assent 
X 
 
 
 
 
 
Obtain Subject Number from IWRS 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical history2 
X 
X 
 
 
 
 
Inclusion/Exclusion criteria2 
X 
X 
 
 
 
 
Previous therapies2 
X 
X 
 
 
 
 
Acne-QoL 
 
X 
 
 
 
X 
Pregnancy Test (FOCBP)4 
X 
X 
X 
X 
X 
X 
Abbreviated physical examination3 
 
X 
 
 
 
X 
Vital sign measurements  
 
X 
 
 
 
X 
Safety labs (CBC/diff, serum chemistry) 
 
X 
 
 
 
X 
EGSS 
X 
X 
X 
X 
X 
X 
Lesion Counts 
X 
X 
X 
X 
X 
X 
Photographs (select sites only) 
 
X 
X 
X 
X 
X 
Cutaneous Safety Evaluation 
 
X 
X 
X 
X 
X 
Tolerability Evaluation 
 
X 
X 
X 
X 
X 
Randomization in IWRS (obtain kit #) 
 
X 
 
X 
X 
 
Administer Subject Instructions (Appendix 17.1) 
 
X 
 
 
 
 
Dispense Study Drug (one tube from IWRS-assigned 
kit) 
 
X 
 
X 
X 
 
Weigh Study Drug to the nearest 0.1gram 
 
X 
X 
X 
X 
X 
Study Drug applied at investigational center 
 
X 
X 
X 
X 
 
Study Drug Collected 
 
 
 
X 
X 
X 
Subject Diary Calendar dispensed 
 
X 
X 
X 
X 
 
Subject Compliance Reviewed / Diary 
 
 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
Concomitant and Prohibited Therapy/Medication 
Review  
X 
X 
X 
X 
X 
X 
End of Study 
 
 
 
 
 
X 
1 If no washout is needed, Visits 1 and 2 may occur on the same day. If a washout is needed, Visit 2 must occur after the appropriate washout period. 
2 Update at baseline visit prior to randomization.  
3 Height will be measured at baseline only; weight measurements and examinations of other abbreviated physical parameters will be performed at Baseline and Week 12. 
4 For pre-menses females and FOCBP, the urine pregnancy test must be completed at all scheduled visits, as per schedule. Serum pregnancy testing will be completed at 
Baseline and Week 12 only. Subjects with a positive pregnancy test at any time during the study will be discontinued. 
5 All Week 12 procedures should be completed for all subjects who terminate early.


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8 Selection and Withdrawal of Subjects 
8.1 
Subject Inclusion Criteria 
Subjects meeting all of the following criteria will be eligible for study entry: 
1. Male or female at least 9 years of age and older;  
2. Written and verbal informed consent must be obtained. Subjects less than age of 
consent must sign an assent for the study and a parent or a legal guardian must sign 
the informed consent (if subject reaches age of consent during the study they should 
be re-consented at the next study visit); 
3. Subject must have a score of 3 (moderate) or 4 (severe) on the Evaluator’s Global 
Severity Score (EGSS) assessment at the baseline visit; 
4. Subjects with facial acne inflammatory lesion (papules, pustules, and nodules) count 
no less than 20 but no more than 50; 
5. Subjects with facial acne non-inflammatory lesion (open and closed comedones) 
count no less than 25 but no more than 100; 
6. Subjects with two or fewer facial nodules;  
7. Females of childbearing potential1 and females who are pre-menses must be willing 
to practice effective contraception for the duration of the study. (Effective 
contraception is defined as stabilized on oral contraceptive for at least 3 months, IUD, 
condom with spermicidal, diaphragm with spermicidal, implant, Nuvaring, injection, 
transdermal patch or abstinence.). Females on birth control pills must have taken the 
same type pill for at least three months prior to entering the study and must not 
change type during the study. Those who have used birth control pills in the past must 
have discontinued usage at least three months prior to the start of the study. Women 
who use birth control for acne control only should be excluded. 
8. Pre-menses females and females of childbearing potential must have a negative urine 
pregnancy test2 at the screening and baseline visits; 
9. Subjects must be willing to comply with study instructions and return to the clinic for 
required visits. Subjects under the age of consent must be accompanied by the parent 
or legal guardian at the time of assent/consent signing; 
10. If a cleanser, moisturizer or sunscreen is needed during the study, Subjects must be 
willing to use only allowed cleansers, moisturizers, sunscreens, or 
                                                 
1 Pre-menses females and Females of Child Bearing Potential (FOCBP) include any female who has not undergone 
successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not 
postmenopausal [defined as amenorrhea >12 consecutive months; or women on hormone replacement therapy 
(HRT) with documented plasma follicle-stimulating hormone (FSH) level >35mLU/mL]. Even women who are 
using oral, implanted or, injectable contraceptive hormones, an intrauterine device (IUD), barrier methods 
(diaphragm, condoms, spermicidal) to prevent pregnancy, practicing abstinence or where partner is sterile (e.g., 
vasectomy), should be considered to be of child bearing potential.            
2   Urine pregnancy tests must have a minimum sensitivity of 25mIU -HCG/mL of urine and must be performed 
within 72 hours prior to the start of study medication. Kits will be provided by the CRO. 


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moisturizer/sunscreen combination products (see Appendix 17.2). The subject must 
agree to use non-comedogenic products (including makeup and shaving products).  
8.2 
Subject Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from the study: 
1. Use of an investigational drug or device within 30 days of enrollment or participation 
in a research study concurrent with this study; 
2. Any dermatological conditions on the face that could interfere with clinical 
evaluations such as acne conglobata, acne fulminans, secondary acne, perioral 
dermatitis, clinically significant rosacea, gram-negative folliculitis, dermatitis, 
eczema; 
3. Any underlying disease(s) or some other dermatological condition of the face that 
requires the use of interfering topical or systemic therapy or makes evaluations and 
lesion count inconclusive; 
4. Subjects with a facial beard or mustache that could interfere with the study 
assessments; 
5. Subjects with more than two (2) facial nodules; 
6. Evidence or history of cosmetic-related acne; 
7. Subject has a history of experiencing significant burning or stinging when applying 
any facial treatment (e.g., make-up, soap, masks, washes, sunscreens, etc.) to their 
face; 
8. Female subjects who are pregnant, nursing mothers, planning a pregnancy during the 
course of the trial, or become pregnant during the study; 
9. Use of estrogens (e.g., Depogen, Depo-Testadiol, Gynogen, Valergen, etc.) for less 
than 12 weeks immediately preceding study entry; Subjects treated with estrogens 12 
or more consecutive weeks immediately prior to study entry need not be excluded 
unless the Subject expects to change dose, drug or discontinue estrogen use during the 
study; 
10. If female, subject has a history of hirsutism, polycystic ovarian disease or clinically 
significant menstrual irregularities;  
11. Treatment of any type of cancer within the last 6 months, with the exception of 
complete surgical excision of skin cancer outside the treatment area; 
12. Subject uses medications and/or vitamins during the study which are reported to 
exacerbate acne (azathioprine, haloperidol, Vitamin D, Vitamin B12, halogens such 
as iodides or bromides, lithium, systemic or mid-to super-high potency 
corticosteroids, phenytoin and phenobarbital); Multivitamins, including Vitamin A, at 
recommended daily doses, and Vitamin D at stable doses, are acceptable; 
13. History of hypersensitivity or allergic reactions to any of the study preparations as 
described in the Investigator’s Brochure, including known sensitivities to any dosage 
form of tazarotene; 


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14. Subjects taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, 
fluoroquinolones, phenothiazines, sulfonamides); 
15. Concomitant use of potentially irritating over-the-counter products that contain 
ingredients such as benzoyl peroxide, alpha-hydroxy acid, salicylic acid, retinol or 
glycolic acids; 
16. Subjects that have not undergone the specified washout period(s) for the following 
topical preparations or physical treatments used on the face or subjects who require 
the concurrent use of any of the following in the treatment area: 
 
     
 
 
 
 
 
 
 
 
 
 
 
If the subject requires topical treatment for acne on areas other than the face (e.g., 
chest and/or back), the investigator may prescribe a product that does not contain 
tazarotene and must be noted in source documents and eCRF. 
 
17. Subjects that have not undergone the specified washout period(s) for the following 
systemic medications or subjects who require the concurrent use of any of the 
following systemic medications: 
 
Corticosteroids (including intramuscular injections)  
(inhaled corticosteroids are allowed)  
4 weeks 
Antibiotics  
4 weeks 
Other systemic acne treatments 
4 weeks 
Systemic retinoids  
6 months 
 
18. Subject intends to use a tanning booth or sunbathe during the study; 
19. Subjects who are unable to communicate or cooperate with the Investigator due to 
language problems, poor mental development, or impaired cerebral function; 
20. Subjects with any underlying disease that the Investigator deems uncontrolled, and 
poses a concern for the subjects safety while participating in the study. 
8.3 
Subject Withdrawal Criteria 
Reasons for withdrawal may include, but are not limited to, the following: 
Topical astringents and abrasives (including comedone 
removal strips) on the face 
1 week 
Non-allowed moisturizers or sunscreens on the face 
1 week 
Antibiotics on the face 
2 weeks 
Other topical anti-acne drugs on the face  
2 weeks 
Soaps containing antimicrobials on the face  
2 weeks 
Anti-inflammatory agents and corticosteroids on the face 
4 weeks 
Retinoids, including retinol on the face  
4 weeks 
Facial procedures, including chemical peel, 
microdermabrasion, light (LED, PDT) and laser therapy, and 
acne surgery 
4 weeks 


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• Acne flare, as determined by the investigator, which requires treatment with a 
disallowed therapy. 
• Either at the investigator's request, for tolerability reasons (e.g., severe adverse 
reactions), or at the subject’s request. 
• When the requirements of the protocol are not followed. 
• When a concomitant therapy likely to interfere with the results of the study is 
reported, or required by the subject (the investigators will report all such information 
on the source documents/electronic case report forms (eCRFs) and decide, in 
accordance with the sponsor, whether the subject is to be withdrawn). 
• When a subject is lost to follow-up. The investigators will try at least twice to reach 
the subject by telephone, email and/or text message and will send a follow-up letter 
by certified mail before considering that the subject is lost to follow-up. These actions 
will be reported on the End of Study source documents and the final eCRF and a copy 
of the follow-up letter maintained in the investigator's file. 
All premature discontinuations and their reasons must be carefully documented by the 
investigator on source documents and the final eCRF, and, if need be, on the AE form. In any 
case, no subject who has been included and has a study number assigned can be replaced by 
another if they discontinue prematurely for whatever reason. All data gathered on the subject 
prior to termination will be made available to the sponsor. 
Reasons for study completion/discontinuation as listed on the final report form are defined as 
follows: 
Normal Study Completion – Subject completes the study as planned in the protocol. 
Adverse Event – Complete AE form. 
Death – Complete SAE form. 
Subject Request – Consent withdrawal, subject moved, schedule conflicts. 
Protocol Violation – Contact the Sponsor or designee before making decision. 
Lost to Follow-Up – Document with at least 2 phone calls, emails and/or text messages and 
a certified letter. 
Pregnancy – Subject will discontinue study drug immediately, but will be followed to term. 
Complete pregnancy and SAE forms if applicable and report to the same contacts using the 
same reporting procedure for an SAE under Section 11.4.6. 
Worsening Condition – Subject requires alternate treatment for acne before the end of the 
study and the investigator determines it is not due to lack of efficacy. 


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Lack of Efficacy – Subject requires alternate treatment for acne after at least 2 weeks of 
study drug treatment and the risk of continuing the subject in the study outweighs the benefit 
as determined by the investigator. 
Withdrawal by Parent/Guardian – An indication that the study participant has been 
removed from the study by the parent or legal guardian. Consent withdrawal, subject moved, 
schedule conflicts. 
Study Terminated by Sponsor – An indication that a clinical study was stopped by its 
Sponsor. 
Other – Specify in comments section of final eCRF. 
Subjects who terminate treatment early will be asked to complete all Week 12 assessments and 
procedures prior to commencement of any alternative therapy for acne (if possible). Subjects 
who discontinue from the study during the treatment period will not be replaced. 
All subjects are free to withdraw from participating in this study at any time and for whatever 
reason, specified or unspecified, and without prejudice. No constraints will be placed on ordinary 
subject management, and subjects, when appropriate, will be placed on other conventional 
therapy upon request or whenever clinically necessary as determined by their physician. 
9 Treatment Plan 
9.1 
Methods of Assigning Subjects to Treatment Groups 
This is a double-blinded study, in which the identity of the study drug will be unknown to 
investigator/evaluator and subjects, as well as all individuals closely associated with the study. 
Subjects will be randomized to 1 of the 2 treatment groups in a ratio of 1:1 (IDP-123 [tazarotene 
0.045%] Lotion: IDP-123 Vehicle Lotion). Each screened subject will be assigned a unique 6-
digit study subject number assigned by the investigational center, which will consist of the 3-
digit investigational center/site number (pre-assigned by sponsor/designee) and the 3 digit 
chronological screening order number, starting with 001 (e.g., 101001, 101002). The study drug 
kit will be assigned to subjects based on a randomization code and kit will be dispensed to the 
subjects by the IWRS at Baseline, Week 4 and Week 8 visits. A study drug log will document 
the inventory and dispensing of study drug at each investigational center. 
9.2 
Randomization and Blinding 
The study drugs will be packaged and labeled identically, and the study drug kits will be 
numbered sequentially and dispensed randomly via IWRS to the subjects entering the study 
within each investigational center. Study drug supplies will be distributed to the investigational 
centers to maintain the randomization ratio within each investigational center. 
As a double-blinded study, the investigators, the site staff, the sponsor, and the clinical monitors 
will not be aware of the treatment assigned to the individual study subjects. Delegated staff 


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members at each investigational center will dispense the study drugs and will collect all used and 
unused study drug tubes as scheduled. 
9.3 
Unblinding  
The treatment assignments for all enrolled subjects will be unblinded only after the conclusion of 
the study. Specifically, the blind will be broken only after all data are verified, entered into the 
database, and validated; subject evaluability assessments are performed and entered into the 
database; and the database is locked. 
In the case of a medical emergency, the investigator can break the blind for the subject involved 
preferably by first discussing the situation with the medical monitor and the sponsor (or 
designee) immediately. After confirmation, the investigator will be contacted with unblinding 
information by a sponsor representative or via IWRS. The investigator will record the code break 
in the subject’s source documents. 
9.4 
Prior and Prohibited Concomitant Medication or Therapy 
Any concomitant medication or therapy stopped for washout as indicated below is to be 
recorded. As noted in the exclusion criteria, there are mandatory washout periods and restrictions 
during the study for the following topical or physical treatments on the face that have a known 
beneficial effect for acne vulgaris: 
 
 
 
 
 
 
 
 
If the subject requires topical treatment for acne on areas other than the face (e.g., chest or back), 
the investigator may prescribe a product that does not contain tazarotene and note in source 
documents and eCRF. 
In addition there is a mandatory wash out period and restrictions during the study for the 
following systemic drugs: 
Topical astringents and abrasives (including comedone removal strips) on 
the face 
1 week 
Non-allowed moisturizers or sunscreens on the face 
1 week 
Antibiotics on the face  
2 weeks 
Other topical anti-acne drugs on the face  
2 weeks 
Soaps containing antimicrobials on the face  
2 weeks 
Anti-inflammatory agents and corticosteroids on the face 
4 weeks 
Retinoids, including retinol on the face  
4 weeks 
Facial procedures, including chemical peel, microdermabrasion, light 
(PDT, LED) and laser therapy, and acne surgery 
4 weeks 


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Corticosteroids (including intramuscular injections) 
(inhaled corticosteroids are allowed)  
4 weeks 
Antibiotics  
4 weeks 
Other systemic acne treatments 
4 weeks 
Systemic retinoids  
6 months 
 
Subjects using concomitant medications or therapies during the course of the study that could 
interfere with the interpretation of the study results (including but not limited to those listed 
above) should not be withdrawn, but the use of the concomitant product should be discontinued. 
No other topical and/or physical treatment (except as noted above) other than the study drug will 
be permitted for acne. 
Information on concomitant medications or therapies will be recorded in the Prior and 
Concomitant Medication or Therapy source document and eCRF. Any therapy used by the 
subject will be considered concomitant therapy (e.g., facial procedures, surgical procedures, 
investigations and operations), and any medication, both over the counter (OTC) or prescription, 
used by the subject will be considered concomitant medication (e.g., aspirin, Tylenol, birth 
control pills, vitamins). Every attempt should be made to keep concomitant medication and 
therapy dosing constant during the study. Any change to concomitant medication or therapy 
should be noted on the Concomitant Therapy or Medication source document and eCRF. 
All cleansers, moisturizers, sunscreens and other topical products used on the treatment area that 
are non-medicated will be captured on the Concomitant Therapy source document and eCRF. 
Subjects must use Investigator approved cleansers, moisturizers, and sunscreens. 
Subjects should avoid excessive UV exposure by such activities as sun bathing or tanning 
booths. Subjects should be instructed to use sunscreens of at least SPF 15 and wear protective 
clothing during the day (e.g., hat). In addition, subjects should be instructed to not use study 
medication on skin that may have become eczematous (on the face) during the course of the 
study. 
9.5 
Treatment Compliance 
Each subject will be instructed on the importance of returning his or her study drug at each 
applicable study visit. If a subject does not return his or her study drug, he or she will be 
instructed to return it as soon as possible. The subjects will bring the tubes dispensed at each 
treatment visit to the next subsequent study visit. Each tube will be weighed on a calibrated scale 
(with the cap on) to the nearest 0.1 gram by a study coordinator or designee prior to dispensation 
and after collection. The subject will also be asked to complete a diary calendar and questioned 
regarding the study drug use since the previous visit in order to judge the subject’s compliance 
with applying the study drug. A subject who deviates significantly from the prescribed 
application amount will be counseled. Any missed applications of study drug will be noted by 


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the subject on the diary, which will be collected and placed in the appropriate source document. 
Missed applications will be documented in the eCRF.  
9.6 
Protocol Deviations and Violations 
The investigators must read the protocol thoroughly and must follow the instructions exactly. 
A deviation from the protocol is an unintended and/or unanticipated departure from the 
procedures and/or processes approved by the sponsor and the IRB/IEC and agreed to by the 
investigator. Deviations usually have an impact on individual subjects or a small group of 
subjects and do not involve inclusion/exclusion or primary endpoint criteria. 
A protocol violation occurs when there is non-adherence to the protocol that results in a 
significant, additional risk to the subject, when the subject or investigator has failed to adhere to 
significant protocol requirements (inclusion/exclusion criteria) and the subject was enrolled 
without prior sponsor approval, or when there is non-adherence to FDA regulations and/or ICH 
GCP guidelines. 
The investigator or designee must document and explain in the subjects’ source documentation 
any deviation from the approved protocol. The investigator may implement a deviation from, or 
a change of, the protocol to eliminate an immediate hazard to study subjects without prior 
IRB/IEC approval. As soon as possible after such an occurrence, the implemented deviation or 
change, the reasons for it, and any proposed protocol amendment(s) should be submitted to the 
IRB/IEC for review and approval, to the sponsor for agreement, and to the regulatory authorities, 
if required. 
10 Study Drug Materials and Management 
The study drug will be dispensed by an appropriately qualified member of the study staff 
assigned by the investigator to this task. 
10.1 IDP-123 Lotion, and IDP-123 Vehicle Lotion  
Chemical structure and formula for the active ingredients in IDP-123 Lotion and IDP-123 
Vehicle Lotion are listed in the tables below:  
Table 2. Drug Substances Identification 
Active Ingredient  
Tazarotene 0.045% 
Chemical Name 
6-[(3,4-Dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl)ethynyl]-3-
pyridinecarboxylic acid ethyl ester 
Chemical Class 
Retinoid 
Molecular Formula 
C21H21NO2S 
CAS Registry Number 
118292-40-3 
 


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Table 3. Test Product Identification  
 
Investigational Product 
Vehicle 
IDP-123 Lotion 
IDP-123 Vehicle Lotion 
Name of Active Ingredient 
Tazarotene 
N/A 
Drug Name / Formulation/ 
Concentration 
IDP-123 Lotion (tazarotene 0.045%) 
IDP-123 Vehicle Lotion 
Manufacturer 
  
  
Valeant Pharmaceuticals International, Inc. 
2150 St. Elzear Blvd West 
Laval (Quebec), Canada H7L 4A8 
Packaging 
45 g tube 
Storage Requirements 
Store at 20°C to 25°C  
(68°F to 77°F) 
Appearance 
White to off-white lotion 
Dosing Schedule 
Once daily x 12 weeks 
Route of Administration 
Topical Application 
10.1.1 Packaging and Labeling 
IDP-123 Lotion and the IDP-123 Vehicle Lotion will be supplied in subject kits. Instructions will 
be provided to the study drug technician responsible at the clinical sites. When a subject is 
randomized into the study, the IWRS specific kit number will be assigned to be used for that 
randomized subject by the IWR system. Each subject kit will contain one tube, which has 45 
grams of study material. A new subject kit will be assigned to a subject at the following visits: 
Baseline, Week 4, and Week 8. The subjects will be dispensed one kit at Baseline as assigned in 
the IWRS. The tube will be weighed on a calibrated scale (with the cap on) to the nearest 0.1 
gram prior to dispensing. The subject will bring the tube to the next study visit (Week 2), where 
it will be collected and weighed to the nearest 0.1 gram (with the cap on) – a new tube will not 
be dispensed at this visit, and the original tube will be returned to the subject. The subject will 
then bring the same tube to the subsequent study visit (Week 4), where it will be collected and 
weighed (with the cap on) to the nearest 0.1 gram; one new tube will be dispensed again by the 
IWRS at Week 4, weighed (with the cap on) to the nearest 0.1 gram and provided to the subject. 
The same will occur at the Week 8 visit. If the subject loses a tube (lost or damaged tube), 
another kit will be dispensed via IWRS. Each tube dispensing will be documented on the drug 
accountability log.   
Each subject kit (and tube) will have a double panel label. Labels will contain, at a minimum, the 
following information: 
• Protocol Number 
• Kit Number 
• Contents 
• Space for entry of the subject initials and subject number 


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• Space for entry of date dispensed 
• The sponsor name, Dow Pharmaceutical Sciences, a division of Valeant 
Pharmaceuticals N.A., LLC 
• The quantity of product (45 grams) 
• A statement reading, “For external use only. Avoid contact with eyes and lips” 
• A statement reading, “Store at controlled room temperature 20°C to 25°C (68°F to 
77°F) with excursions permitted between 15°C to 30°C (59°F to 86°F).” 
• A statement reading, “Caution: New Drug Limited by Federal Law to Investigational 
Use” 
• A statement reading, “Return this product to your investigational site at your next 
visit.” 
10.1.2 Storage, Handling, and Disposal of Study Drug 
The study drug should be stored at controlled room temperature 20°C to 25°C (68°F to 77°F) with 
excursions permitted between 15°C to 30°C (59°F to 86°F), and should not be refrigerated. All 
unused study drug will be sent back to the Sponsor or Sponsor designee upon study completion 
for documented disposal. 
10.1.3 Administration 
The assigned study drug will be applied topically to the face once a day at home, in the evening, 
for 12 weeks (up to the evening prior to Week 12 visit) with the exception of study visit days 
(Baseline, Weeks 2, 4, and 8) where study drug will be applied by the subject after the study visit 
is completed at the investigational center. Study drug will be applied as a thin layer (a dab the 
size of a large pea) that is gently rubbed in to the skin. Study drug use will be limited to the face. 
The Investigator and/or trained investigational center staff member will instruct the subject on 
the proper application procedure of the study drug to the treatment area at the Baseline visit (see 
Appendix 17.1). All subjects will be instructed to apply study drug at approximately the same 
time every day in the evening for 12 weeks (up to the evening of Week 12 visit) after cleansing. 
On study visit days (Baseline, Weeks 2, 4, and 8) subjects should be instructed to wait until after 
their study visit is completed to apply study medication at the investigational site (note, this will 
affect evening application times on study visit days, which is acceptable. Subjects should not 
apply another dose of study drug in the evening on the study visit days). No time interval 
between dosing and meals or any other activity is specified.  
Subjects will be instructed to gently wash their face with a Sponsor/Investigator approved, non-
medicated cleanser and warm (not hot) water. After washing, the subjects will be asked to 
thoroughly rinse and gently pat their face dry. The subjects should use the tube to dispense a pea-
sized amount of study drug to their fingertip and spread a thin layer of the study drug over the 


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entire face. This dose should be dotted on to 6 areas (chin, left cheek, right cheek, nose, left 
forehead, right forehead) on the face. After distributing the dose in this manner the subject 
should gently rub the lotion into the skin. This amount of drug should be sufficient to cover the 
entire face excluding the mouth, eyes, inside the nose, and lips. It is important for the subject to 
treat their entire face (excluding the mouth, eyes and lips) and they should be instructed NOT to 
treat only specific lesions. They should gently smooth the study drug over the face evenly. The 
study drug should become invisible almost immediately following application with gentle 
rubbing. If this does not happen, the Investigator should instruct the subject on the use of a 
smaller dosage. The subject should wash his/her hands after applying the investigational product 
to the face. 
The subjects will be instructed to continue using the same Sponsor/Investigator approved non-
medicated facial cleanser, moisturizer and sunscreen and not to change products during the 
study. At each visit, subjects are to be asked if they have changed their cleansing routine. Facial 
makeup may be applied according to the subject’s normal daily routine; however, subjects 
should be instructed not to wear make-up during study visits as it may interfere with the 
evaluator’s assessments. Subjects must also agree to use non-comedogenic makeup during the 
study if they use makeup. No other products should be used on the face. Subjects should be 
instructed to minimize sun exposure and to use Sponsor/Investigator-approved, non-medicated 
sunscreens of at least SPF 15 and to wear protective clothing during the day (e.g., hat). Subjects 
should also be instructed to not use study treatment on skin that may have become eczematous 
(on the face) during the course of the study.  
Subjects should be instructed to store the study drug at room temperature. If a subject loses or 
misplaces the tube cap at any point during the study, subject should contact the study site to 
return the exposed tube and receive a replacement tube.   
10.2 Study Drug Accountability 
Upon receipt of the study drug, the Investigator is responsible for ensuring that the designated 
investigational center staff member will conduct a complete inventory of study materials and 
assume responsibility for their storage and dispensing. In accordance with federal regulations, 
the investigators must agree to keep all study materials in a secure location with restricted access. 
The Investigator will keep a record of the inventory and dispensing of all study drug. This record 
will be made available to the sponsor’s monitor for the purpose of accounting for all clinical 
supplies. Any significant discrepancy and/or deficiency must be recorded with an explanation. 
All supplies sent to the Investigators will be accounted for and, in no case, used in any 
unauthorized situation. Tubes will be weighed on a calibrated scale to the nearest 0.1 gram (with 
the cap on) before dispensing to and upon return by the subjects, and weights will be recorded on 
the pharmacy log and appropriate eCRF. All used and unused supplies will be returned to 
sponsor/designee for destruction at the conclusion of the study as per sponsor’s direction. 


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11 Study Procedures and Evaluations 
All subject information and data obtained during the study visits will be recorded in the source 
documents, applicable study logs, and eCRFs. 
Evaluators must have appropriate, documented experience and training, or obtain approval from 
the sponsor based on experience (or through additional training organized by the sponsor). 
At each study visit, every attempt should be made to ensure that the same investigator / evaluator 
assesses the same subject.  
11.1 Schedule of Evaluations and Procedures 
11.1.1 Visit 1: Screening Visit (Day -35 to Day 0) 
The following procedures will be conducted at this visit: 
1. Obtain written informed consent prior to performing any study procedures. Subjects less 
than the age of consent must sign an assent form, and the parent or legal guardian must 
sign the informed consent form. 
2. Assign the subject a 6-digit subject number by accessing IWRS, which will consist of the 
3-digit site number (pre-assigned to your site) and the 3-digit chronological order 
screening number, assigned by the IWRS and starting with 101 (e.g., 101001, 101002, 
etc.; in this example site number is 101). 
3. Record the subject’s demographic information. 
4. Record the subject’s medical history. 
5. Record all previous medications (including acne medications) for the past 4 weeks (past 6 
months for systemic retinoids). Record any therapies that will be used concomitantly 
during the study.  
6. Perform Evaluator’s Global Severity Score (EGSS) Assessment followed by 
inflammatory lesion count and non-inflammatory lesion count. 
7. Perform a Urine Pregnancy Test for all females who are pre-menses and females of 
childbearing potential. The urine pregnancy tests will be supplied by the CRO. Verify 
that the subject meets the applicable inclusion/exclusion criteria as outlined in Sections 
8.1 and 8.2. 
8. Discuss allowed cleansers, moisturizers and sunscreens and record any cleanser, 
moisturizer and sunscreen use. (Appendix 17.2). 
9. If subject wears makeup, remind the subject not to wear make-up during any future visits. 
10. If the subject requires a washout, schedule the Baseline visit to occur after the washout is 
complete. If no washout is required, the Screening and Baseline visits may occur on the 
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A urine pregnancy test must be completed at the Screening and Baseline visits prior to 
randomization, and at all scheduled study visits. The decision may be made by the investigator 
to do additional pregnancy tests during the course of the study. 
11.1.2 Visit 2: Baseline Visit (Day 0)  
If a washout is not needed, this visit may occur on the same day as the Screening Visit (Visit 1). 
If a washout is needed, Baseline Visit (Visit 2) must occur after the appropriate washout period 
based on the criteria provided in Section 8.2.  
The following procedures will be conducted at this visit: 
1. The baseline Acne-Specific Quality of Life Questionnaire (Acne-QoL) will be completed 
by the subject and collected prior to any other study-related procedures.   
2. Record any changes in medical history since screening. 
3. Record changes in any concomitant medications or therapies since the previous visit 
under Prior and Concomitant Medications or Therapies. Check for prior and concomitant 
medications / therapies as per Section 9.4. 
4. Perform a Urine Pregnancy Test for all females who are pre-menses and females of 
childbearing potential. The urine pregnancy tests will be supplied by the CRO or CRO 
vendor. 
5. Perform an abbreviated physical examination, including height and weight, and vital 
signs (blood pressure, heart rate, respiration rate and oral temperature). Note: height will 
only be measured at baseline, and not at subsequent visits. Any abnormal physical exam 
findings will be recorded. 
6. Verify that the subject continues to meet the applicable inclusion/exclusion criteria as 
outlined in Sections 8.1 and 8.2. 
7. The Evaluator will perform Baseline efficacy evaluations including the Evaluator’s 
Global Severity Score (EGSS), inflammatory lesion counts, and non-inflammatory lesion 
counts. The EGSS is performed prior to the lesion counting. Every effort should be made 
for the same qualified, validated Evaluator to perform the efficacy evaluations at all visits 
from Baseline to Week 12 for the same subject. 
8. The Evaluator will perform Cutaneous Safety and Tolerability Evaluations. 
9. Collect blood samples for routine laboratory analysis (CBC/Diff, serum chemistry, and 
serum pregnancy for females of childbearing potential). 
10. Select Sites Only – Obtain representative photographs of the face. 
11. Assign the subject the presented kit number (this number will be generated from the 
Interactive Web Response System, [IWRS]).  
12. The study coordinator or designee will weigh the tube (with the cap on) to the nearest 0.1 
gram on a calibrated scale and dispense to the subject. A study diary calendar will also be 
dispensed, and the subject will be instructed to bring it in for his/her subsequent visits. 


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13. The study coordinator or designee will instruct the subject on the proper application 
procedure for the study drug per Section 10.1.3 and will provide written subject use 
instructions to the subject (Appendix 17.1). For the first application, the subject will 
apply the study drug at the investigational center under the direction of the study 
coordinator or designee. The study drug should be applied after all clinical assessments. 
The study coordinator or designee will instruct the subjects to apply the study drug once 
daily at home in the evening up to evening prior to Week 12 visit (study drug will not be 
applied in the evening after this study visit).  
14. The study coordinator will instruct the subject to use a Sponsor/Investigator-approved, 
non-medicated sunscreen of at least SPF 15, and to wear protective clothing during the 
day (e.g., hat). Remind subject not to use study treatment on skin that may become 
eczematous during the study.  
15. Record any AEs or changes in AEs since the screening visit and/or reported 
spontaneously by the subject. 
16. Schedule the next study visit at Week 2 (Day 14 ± 3 days). Remind the subject to not 
apply study drug on day of next study visit, prior to the clinic visit. 
NOTE: At the Baseline and Week 12 visits, serum pregnancy testing is mandatory for 
all females of childbearing potential.  
11.1.3 Visit 3: Week 2 (Day 14 ± 3 Days) Visit 
The following procedures will be conducted at this visit (if a subject terminates early, all final 
visit (Week 12/Final Visit) procedures must be performed): 
1. The Evaluator will perform the efficacy evaluations including the Evaluator’s Global 
Severity Score (EGSS), inflammatory lesion counts, and non-inflammatory lesion counts. 
The EGSS is performed prior to the lesion counting. Every effort should be made for the 
same qualified and validated evaluator to perform the efficacy evaluations at all visits 
from Baseline to Week 12 visit for the same subject. 
2. The Evaluator will perform Cutaneous Safety and Tolerability Evaluations. 
3. Record changes in any concomitant medications since the previous visit under Prior and 
Concomitant Medications or Therapies. Check for prior and concomitant medications / 
therapies as per Section 9.4. 
4. Record any new AEs reported spontaneously by the subject or changes in any ongoing 
AEs. 
5. Perform a Urine Pregnancy Test for all females who are pre-menses and females of 
childbearing potential.  
6. The study drug technician will retrieve and weigh the used study drug with the cap on to 
the nearest 0.1 gram.  Note: a new tube will NOT be dispensed at this visit. The original 
tube will be re-dispensed back to the subject. 
7. The study diary calendar will be collected and reviewed for compliance. Any missed 
doses or deviations should be reported. A new study diary calendar will be dispensed. 


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8. Select Sites Only – Obtain representative photographs of the face. 
9. The study coordinator or designee will remind the subject of the proper technique for 
application of study drug (section 10.1.3). At this visit, the subject will apply the study 
drug at the investigational center under the direction of the study coordinator or designee 
to confirm proper technique. Any necessary retraining can be completed. The study drug 
should be applied after all clinical assessments. The study coordinator or designee will 
remind the subjects to apply the study drug once daily at home in the evening up to 
evening prior to Week 12 visit (study drug will not be applied in the evening after this 
study visit). 
10. The study coordinator will instruct the subject to use a Sponsor/Investigator-approved, 
non-medicated sunscreen of at least SPF 15, and to wear protective clothing during the 
day (e.g., hat). Remind subject not to use study treatment on skin that may have become 
eczematous during the study. 
11. Schedule the next study visit at Week 4 (Day 28 ± 3 days). Remind the subject to not 
apply study drug on day of next study visit, prior to the clinic visit. 
11.1.4 Visit 4: Week 4 (Day 28 ± 3 Days) Visit 
The following procedures will be conducted at this visit (if a subject terminates early, all final 
visit (Week 12 Visit/Final Visit) procedures must be performed): 
1. The Evaluator will perform the efficacy evaluations including the Evaluator’s Global 
Severity Score (EGSS), inflammatory lesion counts, and non-inflammatory lesion counts. 
The EGSS is performed prior to the lesion counting. Every effort should be made for the 
same qualified and validated evaluator to perform the efficacy evaluations at all visits 
from Baseline to Week 12 for the same subject. 
2. The Evaluator will perform Cutaneous Safety and Tolerability Evaluations. 
3. Record changes in any concomitant medications / therapies since the previous visit under 
Prior and Concomitant Medications or Therapies. Check for prior and concomitant 
medications/ therapies as per Section 9.4. 
4. Record any new AEs reported spontaneously by the subject or changes in any ongoing 
AEs. 
5. Perform a Urine Pregnancy Test for all females who are pre-menses and females of 
childbearing potential.  
6. The study drug technician will retrieve and weigh the used study drug tube with the cap 
on to the nearest 0.1 gram. Assign the subject another kit number (this number will be 
generated from the IWRS and dispense a new subject kit of study drug. The new tube 
will be weighed on a calibrated scale with the cap on to the nearest 0.1 gram.  
7. The study diary calendar will be collected and reviewed for compliance. Any missed 
doses or deviations must be reported. A new study diary calendar will be dispensed. 
8. Select Sites Only – Obtain representative photographs of the face.  


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9. The study coordinator or designee will remind the subject of the proper technique for 
application of the study drug (section 10.1.3). At this visit, the subject will apply the 
study drug at the investigational center under the direction of the study coordinator or 
designee to confirm proper technique. Any necessary retraining can be completed. The 
study drug should be applied after all clinical assessments. The study coordinator or 
designee will remind the subjects to apply the study drug once daily at home in the 
evening up to evening prior to Week 12 visit (study drug will not be applied in the 
evening after this study visit). 
10. The study coordinator will instruct the subject to use a Sponsor/Investigator-approved, 
non-medicated sunscreen of at least SPF 15, and to wear protective clothing during the 
day (e.g., hat). Remind subject not to use study treatment on skin that may have become 
eczematous during the study. 
11. Schedule the next study visit at Week 8 (Day 56 ± 3 days). Remind the subject to not 
apply study drug on day of next study visit, prior to the clinic visit. 
11.1.5 Visit 5: Week 8 (Day 56 ± 3 Days) Visit 
The following procedures will be conducted at this visit (if a subject terminates early, all final 
visit (Week 12/Final Visit) procedures must be performed): 
1. The Evaluator will perform the efficacy evaluations including the Evaluator’s Global 
Severity Score (EGSS), inflammatory lesion counts, and non-inflammatory lesion counts. 
The EGSS is performed prior to the lesion counting. Every effort should be made for the 
same qualified and validated evaluator to perform the efficacy evaluations at all visits 
from Baseline to Week 12 for the same subject. 
2. The Evaluator will perform Cutaneous Safety and Tolerability Evaluations. 
3. Record changes in any concomitant medications / therapies since the previous visit under 
Prior and Concomitant Medications or Therapies. Check for prior and concomitant 
medications / therapies as per Section 9.4. 
4. Record any new AEs reported spontaneously by the subject or changes in any ongoing 
AEs. 
5. Perform a Urine Pregnancy Test for all females who are pre-menses and females of 
childbearing potential.  
6. The study drug technician will retrieve and weigh the used study drug tube (with the cap 
on) to the nearest 0.1 gram. Assign the subject another kit number (this number will be 
generated from the IWRS) and dispense a new subject kit of study drug. The new tube 
will be weighed on a calibrated scale (with the cap) on to the nearest 0.1 gram.  
7. The study diary calendar will be collected and reviewed for compliance. Any missed 
doses or deviations should be reported. A new study diary calendar will be dispensed. 
8. Select Sites Only – Obtain representative photographs of the face. 
9. The study coordinator or designee will remind the subject of the proper technique for 
application of the study drug (section 10.1.3). At this visit, the subject will apply the 
study drug at the investigational center under the direction of the study coordinator or 


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designee to confirm proper technique. Any necessary retraining can be completed. The 
study drug should be applied after all clinical assessments. The study coordinator or 
designee will remind the subjects to apply the study drug once daily at home in the 
evening up to evening prior to Week 12 visit (study drug will not be applied in the 
evening after this study visit). 
10. The study coordinator will instruct the subject to use a Sponsor/Investigator-approved, 
non-medicated sunscreen of at least SPF 15, and to wear protective clothing during the 
day (i.e. hat). Remind subject not to use study treatment on skin that may have become 
eczematous during the study. 
11. Schedule the next study visit at Week 12 (Day 84 -3/+5 days). Remind the subject to 
apply study drug up to evening prior to Week 12 visit and not apply study drug on day of 
next study visit, prior to the clinic visit. 
11.1.6 Visit 6: Week 12 (Day 84 -3/+5 Days) Visit – End of Treatment/Study Visit 
The following procedures will be conducted at this visit: 
1. The Week 12 Acne-QoL will be completed by the subject and collected prior to any other 
study-related procedures. 
2. Perform an abbreviated physical exam, including measurements of weight and vital signs 
(blood pressure, heart rate, respiration rate, and oral temperature). Any abnormal physical 
exam findings will be recorded. 
3. The Evaluator will perform the efficacy evaluations including the Evaluator’s Global 
Severity Score (EGSS), inflammatory lesion counts, and non-inflammatory lesion counts. 
The EGSS is performed prior to the lesion counting. Every effort should be made for the 
same qualified and validated Evaluator to perform the efficacy evaluations at all visits 
from Baseline to Week 12 for the same subject. 
4. The Evaluator will perform Cutaneous Safety and Tolerability Evaluations. 
5. Record changes in any concomitant medications / therapies since the previous visit under 
Prior and Concomitant Medications or Therapies. Check for prior and concomitant 
medications / therapies as per Section 9.4. 
6. Record any new AEs reported spontaneously by the subject or changes in any ongoing 
AEs. 
7. The study diary calendar will be collected and reviewed for compliance. Any missed 
doses or deviations must be reported. 
8. The study drug technician will retrieve all study drug tubes from the subject and weigh 
the tubes (with the cap on) on a calibrated scale and record the weight to the nearest 0.1 
gram. 
9. Perform a Urine Pregnancy Test for all females who are pre-menses and females of 
childbearing potential.  
10. Collect blood samples for routine laboratory analysis (CBC/Diff, serum chemistry, and 
serum pregnancy for females of childbearing potential).  


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11. Select Sites Only – Obtain representative photographs of the face. 
12. Exit the subject from the study and complete the end of study eCRFs. 
11.2 Evaluation of Efficacy 
The determination of efficacy will be based on evaluator-blinded assessments of the signs and 
symptoms of acne vulgaris. Evaluators must be a board-certified/board-eligible dermatologist or 
have appropriate documented experience and training, and be present for formal study training 
and validation at the Investigator Meeting (and/or Site Initiation Visit), or obtain a waiver from 
the Sponsor based on experience (or through additional training organized by the Sponsor).  
The EGSS scores and lesion counts will be performed at each study visit. The EGSS scores will 
be collected before the Lesion Counts. All Subject assessments will be performed by a trained 
and validated Evaluator. Every effort should be made to have the same evaluator assess the same 
Subject at each visit. If this is not possible, every effort must be made for the same Evaluator to 
assess the Subject at both the Baseline and Week 12 visits.  
11.2.1 Evaluator’s Global Severity Score (EGSS) 
The Evaluator’s Global Severity Score (EGSS) will be a static assessment that is independent of 
the baseline score. The investigator will make the assessment without referring to the baseline 
value. Every effort should be made for the same evaluator to perform each study assessment for 
the same study subject, for consistency in evaluations.  
Subjects are eligible if they have acne with a global severity of a 3 (moderate) or a 4 (severe) on 
the EGSS at the Baseline visit. The following scores will be used to describe the severity grade 
and subsequent score: 
Table 4.  Evaluator’s Global Severity Score (EGSS) 
Score 
Grade 
Description 
0 
Clear 
Normal, clear skin with no evidence of acne vulgaris 
1 
Almost 
Clear 
Rare non-inflammatory lesions present, with rare non-inflamed papules (papules must 
be resolving and may be hyperpigmented, though not pink-red 
2 
Mild 
Some non-inflammatory lesions are present, with few inflammatory lesions 
(papules/pustules only; no nodulocystic lesions) 
3 
Moderate 
Non-inflammatory lesions predominate, with multiple inflammatory lesions evident: 
several to many comedones and papules/pustules, and there may or may not be one 
nodulocystic lesion 
4 
Severe 
Inflammatory lesions are more apparent, many comedones and papules/pustules, there 
may or may not be up to 2 nodulocystic lesions 
 
11.2.2 Lesion Counts 
The facial area lesion counts will be taken from the subject’s face (including the nose). The 
lesion count groups will be inflammatory and non-inflammatory. Facial inflammatory lesions 
(pustules, papules, and nodules) will be counted as follows: pustules and papules will be counted 


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and recorded together, not separately; nodular lesions will be counted and recorded separately. 
Non-inflammatory lesions (open and closed comedones) will be counted and recorded together. 
The lesions counts will be collected at each visit and/or upon discontinuation. The following are 
definitions of each lesion type counted: 
Inflammatory lesions are defined as follows: 
 
Papule – a solid, elevated lesion less than 5 mm 
Pustule – an elevated lesion containing pus less than 5 mm 
Nodule – palpable subcutaneous lesion greater than 5 mm; has depth, not necessarily elevated 
 
Non-inflammatory lesions are defined as follows: 
 
Open comedones (blackhead) – plugged hair follicle with dilated/open orifice; black in color 
Closed comedones (whitehead) – plugged hair follicle: small opening at skin surface 
11.2.3 Other Assessments 
Photography 
At select sites, photographs of the face will be taken at Baseline and at Weeks 2, 4, 8, and 12. 
Only subjects who provide written photographic consent for facial photographs will be included 
in photography. 
11.3 Evaluation of Safety 
Safety assessments will be conducted at baseline and each subsequent visit.  
11.3.1 Cutaneous Safety Evaluations 
Cutaneous safety will be evaluated through assessment of scaling, erythema, hypo-pigmentation 
and hyper-pigmentation at the drug-application site at the time of the visit. Cutaneous tolerability 
will be evaluated through assessment of selected local signs and symptoms at the drug-
application site: itching, burning and stinging, at the time of the visit.  
Cutaneous safety and tolerability signs and symptoms that result in the subject requiring a 
concomitant therapy, interruption of treatment, or discontinuation from the study, will be 
reported as an AE.  
(Note: To be assessed by the evaluator at the time of the study visit.) 
Scaling: 
0 – None  
No scaling  
1 – Mild  
Barely perceptible, fine scales present on limited areas of the face 
2 – Moderate Fine scale generalized to all areas of the face 
3 – Severe  
Scaling and peeling of skin over all areas of the face 


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Erythema: 
0 – None  
No evidence of erythema present  
1 – Mild  
Slight pink coloration 
2 – Moderate Definite redness 
3 – Severe  
Marked erythema, bright red to dusky dark red in color 
 
Hypo-pigmentation: 
0 – None  
No evidence  
1 – Mild  
Slight, barely perceptible 
2 – Moderate Definite, evident 
3 – Severe  
Marked, prominent 
Hyper-pigmentation: 
0 – None  
No evidence  
1 – Mild  
Slight, barely perceptible 
2 – Moderate Definite, evident 
3 – Severe  
Marked, prominent 
11.3.2 Tolerability Evaluations 
To be reviewed with the subject at the study visit as average over the period since the previous 
visit.  
Itching: 
0 – None   
No itching  
1-   Mild   
Slight itching, not really bothersome  
 
2 – Moderate  Definite itching that is somewhat bothersome 
 
 
3 – Severe  
Intense itching that may interrupt daily activities and/or sleep  
 
Burning: 
0 – None   
No burning 
 
  
1 – Mild  
Slight burning sensation; not really bothersome  
 
2 – Moderate  Definite warm, burning sensation that is somewhat bothersome 
3 – Severe  
Hot burning sensation that causes definite discomfort and may   
 
 
interrupt daily activities and/or sleep  
 
 
Stinging: 
0 – None  
No stinging 
 
  
1 – Mild   
Slight stinging sensation, not really bothersome   
 
2 – Moderate  Definite stinging sensation that is somewhat bothersome 
 
3 – Severe  
Stinging sensation that causes definite discomfort and may interrupt daily 
activities and/or sleep 


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11.3.3 Medical History and Abbreviated Physical Examination 
A medical history will be taken at Screening, and confirmed and revised if needed, at Baseline. 
Medical histories having resolved two or more years before Baseline need not be collected unless 
considered relevant by the investigator. 
An abbreviated physical examination including measurements of height and weight, and vital 
signs (blood pressure, heart rate, respiration rate, and oral temperature) will be performed at 
Baseline and Week 12 (end of treatment/study). Any abnormal physical exam findings will be 
recorded. Note: Height measurement will only be performed at Baseline. 
11.3.4 Laboratory Tests 
Clinical laboratory analyses (CBC/Diff and serum chemistry) will be conducted on blood 
samples collected from subjects at Baseline and Week 12 visit. All results will be reported, 
including results that are abnormal. Clinically significant results, in the opinion of the 
investigator, should be reported as AEs. If an AE should require laboratory testing, the results of 
the test must be obtained by the investigative site and filed in the subject’s documentation.  
For pre-menses females and females of childbearing potential, a serum pregnancy test will be 
conducted at Baseline and Week 12.  
11.3.5 Pregnancy Tests 
All pre-menses females and female subjects of childbearing potential will undergo serum 
pregnancy testing at Baseline and Week 12. In addition, urine pregnancy testing will be 
performed at Screening, prior to randomization at Baseline, and at Weeks 2, 4, 8, and 12. The 
urine pregnancy tests will be supplied by the CRO or CRO vendor. 
11.4 Adverse Events 
11.4.1 Definition of Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a medicinal product and which does not necessarily have a causal relationship with 
the study drug. AEs include any unfavorable and unintended illness, sign, symptom, clinically 
significant laboratory test abnormality, or disease temporally associated with the use of a 
medicinal product that has appeared or worsened during the course of the clinical trial, regardless 
of causal relationship to the study drug(s) under study. AEs include any illness, sign, symptom, 
or out-of-range and clinically significant laboratory finding that has appeared or worsened during 
the course of the clinical trial, regardless of causal relationship to the study. The collection of 
non-serious AEs and serious adverse events (SAEs) will begin following the subject's 
completion of the consent process to participate in the study. 


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11.4.2 Documenting Adverse Experiences 
It is the responsibility of the investigator to document all AEs that occur during the course of the 
study. The AEs should be documented as a single medical diagnosis. When this is not possible, 
the AE should be documented in terms of signs and/or symptoms observed by the investigator or 
reported by the subject at each study visit. Each AE which appears to be independent of any prior 
event will be reported separately. 
All AEs occurring after the subject signs the informed consent through the last study visit must 
be reported, regardless of whether or not the AEs are considered drug-related. All AEs, whether 
in response to a query, observed by the study site personnel, or reported spontaneously by the 
subject, will be recorded. Any AEs deemed related to treatment reported or observed at the final 
study/treatment visit will be followed until stabilization or resolution (or up to 30 days after final 
study visit). 
At each visit during the study, the subject will be assessed for the occurrence of new and ongoing 
AEs. Cutaneous tolerability signs and symptoms that result in the subject’s requiring a 
concomitant therapy, interruption of treatment, or discontinuation from the study will be reported 
as an AE. The following data will be collected on all AEs and recorded on the appropriate eCRF: 
• Event name (diagnosis preferred, if unknown, record the signs/symptoms) 
• Onset date and end date 
• Maximum intensity (severity) 
• Seriousness 
• Action taken regarding study drug 
• Corrective treatment, if given 
• Outcome 
In addition, the investigator’s assessment of causality will be recorded. 
Vital sign abnormalities are to be recorded as AEs only if they are clinically significant (for 
example: are symptomatic, requiring corrective treatment, leading to discontinuation or fulfilling 
a seriousness criterion). 
11.4.3 Serious Adverse Events 
All AEs will be assessed as either serious or non-serious. 
An SAE or serious adverse event is defined as any untoward medical occurrence that at any 
dose: 
• Results in death 


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• Is immediately life threatening, (the term "life threatening" in the definition of 
"serious" refers to an event in which the subject is at risk of death at the time of the 
event; it does not refer to an event which hypothetically might have caused death if it 
were more severe) 
• Requires in patient hospitalization or prolongation of existing hospitalization 
(hospitalization for elective surgery for a baseline condition is not considered an AE) 
• Results in persistent or significant disability/incapacity (permanent or substantial 
disruption of a person’s ability to conduct normal life functions) 
• Is a congenital anomaly/birth defect 
• Is a medically important event that may not be immediately life threatening or result 
in death or hospitalization, but may jeopardize the subject and may require medical or 
surgical intervention to prevent one of the above listed outcomes. Examples of such 
events include, but are not limited to, allergic bronchospasm requiring intensive 
treatment in an emergency room or at home; blood dyscrasias or convulsions that do 
not result in inpatient hospitalization. 
Note: A spontaneous abortion will be considered an SAE and must be reported per Reporting of 
SAEs under Section 11.4.6. 
11.4.4 Assessment of Severity 
The severity assigned to an AE should be determined by the maximum severity of the AE. The 
categories described below should be used to estimate the severity of AEs: 
• Mild: Transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required 
• Moderate: Mild to moderate limitation in activity; some assistance may be needed; no 
or minimal medical intervention/therapy required 
• Severe: Marked limitation in activity; some assistance usually required; medical 
intervention/therapy required; hospitalization or prolongation of current 
hospitalization possible; may be incapacitating or life threatening 
11.4.5 Assessment of Causality 
The investigator should assess the relationship of the AE, if any, to the study drug as either 
“Related” or “Not Related”. The following should be taken into account when assessing AE/SAE 
causality: 
Related: There is at least a reasonable possibility that the AE/SAE is related to the study drug. 
Reasonable possibility means that there is evidence to suggest a causal relationship between the 
drug and the AE/SAE. 


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Not Related: There is little or no reasonable possibility that the AE/SAE is related to the study 
drug. This assessment implies that the AE/SAE has little or no temporal relationship to the study 
drug and/or a more likely or certain alternative etiology exists.  
11.4.6 Reporting of Serious Adverse Events 
Adverse events classified as “serious” require expeditious handling and reporting to sponsor or 
designee within 24 hours of investigational center notification to comply with regulatory 
requirements. 
All SAEs, whether related or unrelated to study drug, must be immediately reported to the 
Medical Monitor and CRO contact within 24 hours of the investigator’s awareness of the event. 
All SAEs must be reported via confirmed facsimile or email transmission and must be submitted 
on a written SAE report form signed by the investigator within 24 hours of the investigator’s 
awareness of the event. 
The contact(s) for reporting an SAE are: 
 
 
Investigators should not wait to receive additional information to fully document the event 
before notifying the Medical Monitor and Sponsor of an SAE. If only limited information is 
initially available, follow-up reports are required. Additional relevant information such as 
hospital records and autopsy reports should be provided to the Sponsor as soon as they are 
available. Should the investigator become aware of an SAE (regardless of its relationship to 
investigational product) that occurs within 30 days after stopping the study drug, the SAE must 
be reported in accordance with procedures specified in this protocol. 
 
All deaths of subjects, regardless of cause, and which are known to the Investigator will be 
reported on the appropriate eCRF for up to 30 days after the administration of study drug, 
regardless of the Investigator's opinion regarding drug relationship. Documentation of the 
subject’s cause of death and a copy of the autopsy or hospital report will also be provided. The 
Medical Monitor and CRO contact must be notified within 24 hours of knowledge of the event 
by telephone (and/or facsimile/email) of all subject deaths. Written follow-up must be received 


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by the medical monitor and the Institutional Review Board/Independent Ethics Committee 
(IRB/IEC) within five (5) calendar days of initial notification. 
 
The investigator should take all appropriate measures to ensure the safety of the subjects, notably 
he/she should follow a subject with an SAE until the event has resolved or the condition has 
stabilized. This may imply that follow-up will continue after the subject has left the study, and 
that additional investigations may be requested by the Sponsor. When a SAE persists at the end 
of the study, the Investigator will conduct follow-up contacts with the subject until the 
Investigator/Sponsor agree the event is satisfactorily resolved and/or stabilized. If at any time 
after 30 days after administration of study drug, the investigator becomes aware of an SAE 
which he/she feels is related to study drug or procedure, this must also be reported immediately 
(within 24 hours of knowledge of occurrence) by telephone and confirmed facsimile 
transmission/email to the Medical Monitor and Sponsor and/or Sponsor designee. 
11.4.7 Expedited Serious Adverse Event Reports 
An AE, whether serious or non-serious, is designated unexpected (unlabeled) if it is not reported 
in the clinical safety section of the Investigator Brochure or if the event is of greater frequency, 
specificity or severity. 
Expedited SAE reports are those that are both unexpected based on the reference document 
(Investigator Brochure) and are related (i.e., the relationship cannot be ruled out) to the study 
drug. These expedited reports are subject to reporting timelines of 7 and/or 15 calendar days to 
the regulatory reporting agency(ies). The Sponsor will notify regulatory authorities of these AEs 
and all participating investigational centers in writing for submission by the investigator to the 
IRB/IEC. This notification will be in the form of a Safety Update to the Investigator Brochure 
(i.e., “15-day letter”). 
Upon receiving such notices, the investigator must review and retain the notice with the 
Investigator Brochure and immediately submit a copy of this information to the responsible 
IRB/IEC according to local regulations. The investigator and IRB/IEC will determine if the 
informed consent requires revision. The investigator should also comply with the IRB/IEC 
procedures for reporting any other safety information. 
11.4.8 Pregnancy 
All pre-menses females and female subjects of childbearing potential must use an effective 
method of birth control during the course of the study, in a manner such that risk of contraceptive 
failure is minimized. Abstinence is allowed as a birth control method. 
Before enrolling a pre-menses female or female subject of childbearing potential in this clinical 
trial, the investigator must review the following information about study participation: 
• Informed consent requirements 


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• Contraceptives in current use 
Following review of this information and appropriate subject counseling, the investigator or 
designee and the subject must sign the informed consent before study enrollment. 
During the study, all female subjects of childbearing potential should be instructed to contact the 
investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual 
period). 
If a subject or investigator suspects that the subject may be pregnant prior to study enrollment, 
the study drug must be withheld until the results of laboratory pregnancy testing are available. If 
pregnancy is confirmed, the subject must not receive study drug and must not be enrolled in the 
study. If pregnancy is suspected while the subject is receiving study treatment, the study drug 
must immediately be withheld until the result of pregnancy testing is known. If pregnancy is 
confirmed, the study drug will be permanently discontinued and the subject will be followed 
until the pregnancy comes to term. A Pregnancy Report form will be submitted to the Sponsor, 
initially and at the end of the pregnancy, which includes the outcome of the pregnancy and any 
complications occurring during the pregnancy or the delivery. 
All confirmed pregnancies must be immediately reported to the Medical Monitor and CRO 
contact within 24 hours of the investigator’s awareness of the pregnancy. All confirmed 
pregnancies are to be reported on a pregnancy form using the same reporting procedure for an 
SAE under Section 11.4.6. 
12 Statistics 
All statistical processing will be performed using SAS® version 9.3 or later unless otherwise 
stated. Statistical significance will be based on two-tailed tests of the null hypothesis resulting in 
p-values of 0.05 or less. 
The primary method of handling missing efficacy data will be based on estimation using the 
method of Markov Chain Monte Carlo (MCMC) imputation.  This method provides robust 
estimation when the pattern of missingness is arbitrary.  Additionally, the estimation will be done 
for each treatment group separately so that the pattern of missingness for one group does not 
influence the estimation of missing data for another group.  Groups of complete datasets 
following the estimation will be concatenated to form analysis datasets for the comparative 
analyses and subsequent imputation result inference with SAS PROC MIANALYZE. 
Descriptive statistics will also be derived from the multiply imputed datasets. 
Additionally, a model-based multiple imputation process will be used as a sensitivity analysis to 
the MCMC imputation. Finally, the absolute change in lesion count will be analyzed using a 
repeated measures ANCOVA for lesion count data or a repeated measures logistic regression 
model (generalized estimating equations) for the dichotomized EGSS. 


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A statistical analysis plan (SAP), describing all statistical analyses will be provided as a separate 
document. The SAP will be finalized prior to unblinding of the study treatments. 
Evaluations and Analyses 
Inflammatory lesions and non-inflammatory lesions will be recorded for each subject at Baseline 
and at Weeks 2, 4, 8, and 12. The absolute and percent change from baseline of inflammatory 
lesions and non-inflammatory lesions will be derived for each subject at Weeks 2, 4, 8, and 12. 
The EGSS will be recorded for each Subject. The EGSS will be dichotomized into “success” and 
“failure” at Week 2, 4, 8, and 12 with a subject considered a success for those visits if the EGSS 
is at least 2 grades less than baseline and are Clear or Almost Clear.  
Subjects will be asked to complete the Acne-Specific Quality of Life Questionnaire at Baseline 
and Week 12.  
All assessments will be conducted for both ITT and PP. 
12.1 Assessment of Efficacy 
Primary, secondary, and supportive efficacy analyses will be conducted on the ITT (primary) 
population. Primary efficacy analyses will be conducted on the PP (supportive) population. 
12.1.1 Primary Efficacy 
There are three co-primary efficacy endpoints: 
• Absolute change in inflammatory lesion count from Baseline to Week 12 
• Absolute change in non-inflammatory lesion count from Baseline to Week 12 
• Proportion of subjects who have at least a 2 grade reduction at Week 12 from 
Baseline in the Evaluator's Global Severity Score and are Clear or Almost Clear 
12.1.2 Secondary Efficacy 
The secondary efficacy endpoints will be the following: 
• Percent change in inflammatory lesion count from Baseline to Week 12 
• Percent change in non-inflammatory lesion count from Baseline to Week 12 
• Proportion of subjects who have at least a 2 grade reduction at Week 12 from 
Baseline in the Evaluator's Global Severity Score 
• Percent change in inflammatory lesion count from Baseline to Week 8 
• Percent change in non-inflammatory lesion count from Baseline to Week 8 
• Percent change in inflammatory lesion count from Baseline to Week 4 
• Percent change in non-inflammatory lesion count from Baseline to Week 4 
12.1.3 Supportive Efficacy 
 The supportive efficacy endpoints will be as follows: 


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• Percent change in inflammatory lesion count from Baseline to Week 2 
• Percent change in non-inflammatory lesion count from Baseline to Week 2 
• Proportion of subjects who have at least a 2 grade reduction at Week 8 from Baseline 
in the Evaluator's Global Severity Score 
• Proportion of subjects who have at least a 2 grade reduction at Week 4 from Baseline 
in the Evaluator's Global Severity Score 
• Proportion of subjects who have at least a 2 grade reduction at Week 2 from Baseline 
in the Evaluator's Global Severity Score 
12.1.4 Test of Superiority for Lesion Count Variables  
This section provides the basic model and statistical approach which is used in combination with 
the multiple imputation procedures described in Section 12.1.9. Tests of superiority for the 
absolute change from Baseline in inflammatory and non-inflammatory lesions will be based on 
either parametric or non-parametric methods consistent with the statistical assumptions required 
to support the analyses. Specifically, the tests of superiority will be based on an ANCOVA with 
factors of treatment and analysis center and the respective Baseline lesion count as a covariate or 
on ranked data submitted to an ANCOVA with factors of treatment and analysis center and the 
respective Baseline lesion count as a covariate.  If the treatment-by-analysis center interaction 
effect is significant at an alpha less than 0.10, then the effect will be included in the model; 
otherwise it will be removed. 
A skewness test, based on the methods presented by J.H. Zar (1984) [10], will be applied to the 
residuals resulting from an ANCOVA. A two-sided p-value for the skewness test significant at 
0.01 will imply the use of the non-parametric method. If a parametric analysis is indicated, the 
results of the parametric analysis will be considered the primary analysis. Should a non-
parametric analysis be indicated, the absolute or percent changes in inflammatory and non-
inflammatory lesions will be rank transformed prior to submitting them to the ANCOVA. 
Results of the rank-transformed analyses then will be considered the primary analysis; however, 
results of the non-ranked transformed analyses will also be presented. 
12.1.5 Test of Superiority for EGSS 
The EGSS will be dichotomized into “success” and “failure” with a subject considered a success 
for those visits if the Evaluator’s Global Severity Score is at least 2 grades less than Baseline and 
are Clear or Almost Clear. The analysis of the dichotomized Evaluator's Global Severity Score 
will be based on a logistic regression test with factors of treatment group and analysis center. 
12.1.6 Statistical Hypothesis Testing and Control of Multiplicity 
Statistical hypothesis testing for lesion count analyses will use the statistical model introduced in 
Section 12.1.4 and employs the methods of Section 12.1.9 regarding missing values. The 
analysis of the dichotomized Evaluator's Global Severity Score will be based on the logistic 


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regression with factors of treatment group and analysis center and employs the methods of 
Section 12.1.9 regarding missing values.  
The overall Type I error will be controlled by requiring the three co-primary efficacy endpoints 
to be statistically significant. Specifically, failure of any one of the primary efficacy endpoints 
will invalidate the statistical significance of the secondary efficacy endpoints. 
The following stepwise process will be conducted for testing the secondary efficacy endpoints in 
order to control for multiplicity. These tests will be performed for only the ITT population. The 
testing process will terminate whenever a statistical test for a step is not significant. All 
subsequent tests for the remaining steps will be considered not significant. The order of testing 
is:  
 
Step 
Number 
Secondary Endpoint 
1 
Percent change in non-inflammatory lesion count from Baseline to Week 12 
2 
Percent change in inflammatory lesion count from Baseline to Week 12 
3 
Proportion of subjects who have at least a 2 grade reduction at Week 12 from 
Baseline in the Evaluator's Global Severity Score 
4 
Percent change in non-inflammatory lesion count from Baseline to Week 8 
5 
Percent change in inflammatory lesion count from Baseline to Week 8 
6 
Percent change in non-inflammatory lesion count from Baseline to Week 4 
7 
Percent change in inflammatory lesion count from Baseline to Week 4 
 
The following stepwise process will be conducted for testing the supportive efficacy endpoints in 
order to control for multiplicity. These tests will be performed for only the ITT population. In 
order to control for multiplicity, failure of any one of the secondary efficacy endpoints will 
invalidate the statistical significance of the supportive efficacy endpoints. The testing process 
will terminate whenever a statistical test for a step is not significant. All subsequent tests for the 
remaining steps will be considered not significant. The order of testing is:  
Step 
Number 
Supportive Endpoint 
1 
Percent change in non-inflammatory lesion count from Baseline to Week 2 
2 
Percent change in inflammatory lesion count from Baseline to Week 2 
3 
Proportion of subjects who have at least a 2 grade reduction at Week 8 from 


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Baseline in the Evaluator's Global Severity Score 
4 
Proportion of subjects who have at least a 2 grade reduction at Week 4 from 
Baseline in the Evaluator's Global Severity Score 
5 
Proportion of subjects who have at least a 2 grade reduction at Week 2 from 
Baseline in the Evaluator's Global Severity Score 
 
12.1.7 Descriptive Statistics 
Descriptive statistics will be presented for the following parameters by treatment group for both 
the ITT and PP populations: 
• Frequency and percent distributions of the Evaluator’s Global Severity Score at 
Baseline and Weeks 2, 4, 8, and 12. 
• Frequency and percent distributions of the dichotomized Evaluator’s Global Severity 
Score at Baseline and Weeks 2, 4, 8, and 12. 
• Descriptive statistics including mean, median, standard deviation, minimum, and 
maximum will be used to summarize inflammatory and non-inflammatory lesion 
counts at Baseline and Weeks 2, 4, 8, and 12.   
• Descriptive statistics including mean, median, standard deviation, minimum, and 
maximum will be used to summarize the absolute and percent change in 
inflammatory and non-inflammatory lesion counts at Weeks 2, 4, 8, and 12. 
12.1.8 Pooling Analysis 
The clinical study will be conducted under a common protocol for each investigational site with 
the intention of pooling the data for analysis.  Every effort will be made to promote consistency 
in study execution at each investigational site. The study is intended to be conducted in a manner 
such that a minimum of 5 subjects will be enrolled in each treatment arm for any investigator.  In 
the event that there are too few subjects in a treatment arm for an investigator, then this 
investigator's data will be combined to achieve the desired sample size minimum per arm.  The 
combining of investigator's data will be accomplished by taking the investigator with the 
smallest enrollment and combining it with the investigator with the largest enrollment.  If there is 
a further need to combine data, then the data of the investigator with the second smallest 
enrollment will be combined with the investigator's data which had the second largest 
enrollment, and so on.  This process will continue for all investigators who did not have a 
minimum of 5 subjects per treatment arm.  The process of combining investigator data that have 
insufficient subjects per treatment arm will result in redefining the groups of investigators for the 
purposes of statistical analyses.  These combined groups will be referred to as "analysis centers" 
in the statistical analyses based on ANCOVA and stratified logistic testing.  
Prior to investigating the treatment effect within the analysis centers, the magnitude of the site 
main effect will be investigated to determine if the main site-to-site variability is such that it 


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could mask the analysis center effects. Thus, if computationally possible, a one-way ANCOVA 
(for lesion count variables) or a logistic regression analysis (for EGSS) with a factor of site will 
be conducted prior to pooling. If the data structure interferes with the logistic regression, a 
descriptive analysis of the site effect will be undertaken. Conclusions appropriate to the findings 
of this step will be presented. 
The consistency of treatment response will be investigated across the analysis centers subsequent 
to combining the data as described above.  Statistical tests will be conducted to identify if there 
are extreme analysis centers that could affect the interpretation of common statistical and clinical 
conclusions.  An analysis center by treatment interaction will be included in the primary and 
secondary variable analyses to test for parallel treatment effect at an alpha level of 0.10.  Change 
from baseline in inflammatory lesions and non-inflammatory lesions will be analyzed with an 
ANCOVA (unranked or ranked) with factors of treatment, analysis center, and treatment by 
analysis center interaction and the respective baseline lesion count variable as a covariate.  For 
the purpose of testing consistency of treatment response, the dichotomized EGSS will be 
analyzed with a logistic regression procedure with factors of treatment, analysis center, and 
treatment by analysis center interaction. Further examination will follow for any variables that 
have a significant ANCOVA or logistic regression interaction term.  In the event that the 
ANCOVA or logistic regression interaction (referred to henceforth as the "appropriate test") p-
value is less than or equal to 0.10, a sensitivity analysis that excludes analysis centers with the 
extreme efficacy result will be performed to determine the robustness of the treatment effect.  On 
the other hand, if the outcome of the appropriate test has a p-value greater than 0.10, then the 
conclusions from the pooled data will be considered to be free of the impact of extreme analysis 
centers. 
The first step in conducting a sensitivity analysis is to identify the extreme analysis center or 
centers that contribute to the statistical significance of the appropriate test.  The process involves 
submitting subsets of analysis centers to the appropriate test and observing the appropriate test p-
value for the subset.  Subsets with p-values greater than 0.10 for the appropriate test are 
considered homogeneous. 
The search for an extreme analysis center begins by analyzing all subsets that can be created by 
excluding one analysis center.  If one or more of the subsets result in an appropriate test p-value 
greater than or equal to 0.10, then the analysis center excluded from the subset with the largest p-
value for the appropriate test is deemed to be the extreme analysis center. 
If all appropriate test subset p-values are less than or equal to 0.10, then the process will analyze 
the appropriate test for all subsets that can be created by excluding two analysis centers.  If one 
or more of these subsets generate appropriate test p-values larger than 0.10, then the analysis 
centers excluded from the subset with the largest appropriate test p-value are deemed the extreme 
analysis centers. 


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Thus, the process of identifying the extreme analysis centers will continue in a stepwise manner 
by first excluding one, then two, then three, etc., analysis centers until the appropriate test p-
value exceeds 0.10. 
Once the extreme analysis center or centers have been identified, then the treatment p-values of 
the remaining analysis centers will be computed.  Inferences will be drawn from the treatment p-
value, as well as any pertinent observations regarding the extreme analysis center or centers.  
Additionally, it is noted that this process excludes subjects from the analysis in a non-random 
manner and has an unpredictable impact on the power of the treatment effect test.  In the event 
that the treatment effect of the remaining subset is not statistically significant, due consideration 
of the post-hoc aspects of the process will be given when the results are interpreted.  Conclusions 
will be presented by the sponsor as appropriate to the findings of the sensitivity analysis. 
12.1.9 Missing Efficacy Data Imputations 
Lesion Count Variable Missing Data Imputation 
Missing 12 week data will be estimated by multiple imputation and subsequently analyzed. 
Missing lesion count data will be derived for the analysis using the method of Markov Chain 
Monte Carlo (MCMC) multiple imputation which does not rely on the assumption of data 
missing at random. Additionally, the pattern of missing observations in each treatment group 
cannot influence the missing value estimation in the other because the imputation is being 
conducted independently for each treatment group. 
Multiple imputation and subsequent analysis will involve 4 distinct phases with these principal 
tasks: 
 
1. Calculate the number of missing values to be estimated by MCMC (nmiss) for 12 week 
value. 
2. Create a data set of subjects, one for each treatment group, with observed values and 
those needing estimation by MCMC.  The missing lesion count values in each data set 
will be filled in using the MCMC method ‘5 x nmiss’ times to generate ‘5 x nmiss’ data 
sets.  The resulting data sets for each treatment arm will be combined into one complete 
data set for each imputation. 
Syntax: 
proc mi data=datain out=dataout seed=&seed. nimpute=5xnmiss <options>; 
where trtpn=(1, or 2); 
mcmc chain=multiple; 
var baseline week4 week8 week12; 
run; 
3. For each complete data set, the absolute change in lesion counts for baseline minus the 12 
week value will be computed. Each complete data set will be analyzed as specified for 
the particular analysis. 


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4. The results from these analyses will be combined into a single inference using SAS 
PROC MIANALYZE. 
A total of 4 random seeds will be needed to impute inflammatory lesion counts from non-
inflammatory lesion counts for the two treatment groups. Those 4 random seeds have been pre-
specified by using a random number generator: 
• 
Inflammatory Lesion Counts; IDP-123 Lotion: Seed= 944205156 
• 
Inflammatory Lesion Counts; IDP-123 Vehicle Lotion: Seed= 199742700 
• 
Non-Inflammatory Lesion Counts; IDP-123 Lotion: Seed= 204439619 
• 
Non-Inflammatory Lesion Counts; IDP-123 Vehicle Lotion: Seed= 652160167 
EGSS Missing Data Imputation 
A similar procedure will be used for the analyses based on proportion of EGSS successes 
wherein the ANCOVA analysis is replaced with a logistic regression analysis.  Specifically, 
missing 12 week EGSS values from which the dichotomized EGSS is derived will be estimated 
by (MCMC) which does not rely on the assumption of data missing at random. Additionally, the 
pattern of missing observations in each treatment group cannot influence the missing value 
estimation in the other because the imputation is being conducted independently for each 
treatment group. 
The missing 12 week EGSS values will be derived for the analysis using the method of Markov 
Chain Monte Carlo (MCMC) multiple imputation. Multiple imputation and subsequent analysis 
will involve 4 principal tasks: 
1. Calculate the number of missing values to be estimated by MCMC (nmiss) for 12 week 
value. 
2. Create a data set, one for each treatment group, of subjects with observed values and 
those needing estimation by MCMC.  The missing EGSS values in each data set will be 
filled in using the MCMC method ‘5 x nmiss’ times to generate ‘5 x nmiss’ data sets. The 
resulting data sets for each treatment arm will be combined into one complete data set by 
imputation. 
Syntax: 
proc mi data=datain out=dataout seed=&seed. nimpute=5xnmiss <options>; 
  where trtpn=(1, or 2); 
  mcmc chain=multiple; 
  var baseline week4 week8 week12; 
run; 
3. For each complete data set, the dichotomous success rate (clear or almost clear with a 2-
point change from baseline) will be computed. The 12-week estimated global values will 


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be rounded to the nearest integer value prior to evaluating the success rate. Each 
complete data set will be analyzed with a logistic regression with factors of treatment 
group and analysis center. 
4. The results from these analyses will be combined into a single inference using SAS 
PROC MIANALYZE. 
A total of 2 random seeds will be needed to impute EGSS for the two treatment groups. Those 2 
random seeds have been pre-specified by using a random number generator: 
• 
EGSS; IDP-123 Lotion: Seed= 910346358 
• 
EGSS; IDP-123 Vehicle Lotion: Seed= 1726246005 
12.1.10  Sensitivity Efficacy Analyses 
Sensitivity analyses for absolute change in lesion count 
The first sensitivity analysis for absolute change in lesion count will use a repeated measures 
ANCOVA, with treatment, analysis center, and visit (ie, Week 4, Week 8) as independent factors 
and a covariate of baseline lesion count.  In this analysis, data from all post-baseline visits will 
be included with no imputation for missing data. 
The second sensitivity analysis will use the model based multiple imputation method to impute 
missing data for the absolute change in lesion counts at Week 12.  Although the full details will 
be presented in the Statistical Analysis Plan (SAP), the multiple imputation will involve 4 
principal tasks: 
1. Calculate the number of missing values (nmiss) for absolute change in lesion counts. 
2. Missing values will be filled in ‘5 x nmiss’ times to generate ‘5 x nmiss’ complete data 
sets.  The imputation model used will be an ANCOVA with factors of treatment group 
and analysis center, and a covariate of baseline lesion count (ie, the imputation model 
will be the same as the analysis model). Appropriate modifications will be made should 
the analysis be based on a non-parametric method. 
3. Each complete data set will be analyzed with an ANCOVA with factors of treatment 
group, and analysis center, and a covariate of baseline lesion count. 
4. Results from these analyses will be combined into a single inference. 
Sensitivity analyses for EGSS 
The first sensitivity analysis for the dichotomized EGSS success will use a repeated measures 
logistic regression model (generalized estimating equations), with dichotomized EGSS success 
as the dependent variable and treatment, analysis center, and visit (i.e., Week 4, Week 8) as 
independent factors.  In this analysis, data from all post-baseline visits will be included with no 
imputation for missing data. 


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The second sensitivity analysis will use the model based multiple imputation method to impute 
missing data for the dichotomized EGSS data. Although the full details will be presented in the 
SAP, the multiple imputation will involve 4 principal tasks: 
1. Calculate the number of missing values (nmiss) for dichotomized EGSS success. 
2. Missing values will be filled in ‘5 x nmiss’ times to generate ‘5 x nmiss’ complete data 
sets.  The imputation model used logistic regression with factors of treatment group and 
analysis center (ie, the imputation model will be the same as the analysis model). 
3. Each complete data set will be analyzed with a logistic regression a factors of treatment 
group and analysis center. 
4. Results from these analyses will be combined into a single inference. 
12.1.11  Subgroup Analyses 
Subset analyses will be conducted for the ITT populations for the subgroups baseline global 
severity, gender, age, ethnicity, and race. Age will be dichotomized to less than the median age 
of subjects and greater than or equal to the median age of subjects. An additional analysis will 
include age with categories of less than 18 and 18 to less than the median age and greater than or 
equal to the median age. Subset analyses will be conducted on the variables absolute change 
from baseline in inflammatory lesions and non-inflammatory lesions at Week 12 as well as the 
dichotomized global severity score at Week 12.  These analyses will contain only descriptive 
statistics. 
12.1.12  Subject Self-Assessments 
Subjects will be asked to complete the Acne-Specific Quality of Life Questionnaire (Appendix 
17.3).  Descriptive statistics will be used to summarize the data reported for the questionnaire. 
No inferential analyses will be conducted.  
12.2 Assessment of Safety 
Safety will be evaluated by tabulations of adverse events (AEs), Cutaneous Safety Evaluation, 
and Tolerability Evaluations. Cutaneous Safety Evaluation scores (erythema, scaling, and 
hypo/hyper-pigmentation) and Tolerability (itching, burning, and stinging) will be presented with 
descriptive statistics at Baseline and at Weeks 2, 4, 8, and 12 for each treatment group. 
Frequencies and percentages for each outcome category will be included in these statistics. Mean 
values will be presented graphically by week and treatment group. 
12.2.1 Adverse Events 
All adverse events occurring during the study will be recorded and classified on the basis of 
MedDRA terminology. Descriptions of AEs will include the date of onset, the date the AE 
ended, the severity of the AE, the relationship to study medication, the action taken regarding 


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study medication usage, the action taken to treat the AE, and the outcome. All reported 
treatment-emergent AEs (TEAEs) will be summarized by the number of subjects reporting AEs, 
system organ class, severity, seriousness, and relationship to study medication. TEAEs are those 
AEs with an onset on or after the date of the first study drug application. 
Adverse events will be summarized by treatment group and severity.  Each subject will be 
counted only once within a system organ class or a preferred term by using the adverse events 
with the highest severity within each category. 
Adverse events will be summarized by treatment group and relationship to study medication.  
Each subject will be counted only once within a system organ class or a preferred term by using 
the adverse events with the greatest relationship within each category. 
Comparisons among treatment groups will be made by tabulating the frequency of subjects with 
one or more AEs (classified into MedDRA terms) during the study.  The Fisher’s Exact test will 
be used to compare the proportion of subjects in each treatment group who report any adverse 
event at a significance level of 0.05.  The specific system organ classes and preferred terms 
analyzed will be those that are reported by at least one percent of the subjects in any treatment 
group. 
All information pertaining to AEs noted during the study will be listed by subject, detailing 
verbatim given by the investigator, preferred term, system organ class, start date, stop date, 
severity, actions taken, and drug relatedness. The AE onset will also be shown relative (in 
number of days) to the day of initial dose of the randomized study medication. 
Serious adverse events (SAEs) will be tabulated by subject within treatment groups. 
In addition, a list of subjects who discontinued from the study and a list of subjects who 
experienced SAEs will also be provided. 
12.2.2 Safety Laboratory Tests 
Changes from baseline in safety laboratory values will be summarized with descriptive statistics 
at all applicable study visits. Shift tables will be presented for changes in safety laboratory 
values. Normal ranges established by the central laboratory will be used to determine the shifts. 
A listing of all out-of-range laboratory test results at any assessment time point will also be 
provided. Determination of clinical significance for all out-of-range laboratory values will be 
made by each investigator and included in the listing. In addition, a listing of all clinically 
significant laboratory test results will be provided. 
12.2.3 Vital Sign Measurements 
Vital signs as well as changes from Baseline in vital sign measurements will be summarized with 
descriptive statistics for each treatment group at all applicable study visits. 


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12.2.4 Concomitant Medications 
All previous concomitant medications will be classified based on terminology from the WHO 
Drug Dictionary. Previous therapies and concomitant medications data will be presented in data 
listings. 
12.3 Subject Disposition 
A tabulation of subject disposition will be provided. The tabulation will include the numbers of 
subjects who enter the study, complete the study, and discontinue the study. The reasons for 
discontinuation will be included. 
12.4 Demographics and Baseline Characteristics 
Subject demographic and baseline characteristics will be summarized by treatment group for the 
ITT, PP, and safety populations. For continuous variables (e.g. age) comparisons among the two 
treatment groups will be conducted using a two-way analysis of variance (ANOVA) with factors 
of treatment group and analysis center. Ethnicity and race will be analyzed with a Cochran-
Mantel-Haenszel test stratified by analysis center. Past and current medical conditions, as well as 
history of disease will be presented in a data listing. 
12.5 Protocol Deviations 
All protocol deviations will be reported to the sponsor and recorded throughout the study. A 
tabulation of protocol deviations will be presented in a data listing. 
12.6 Compliance 
No formal evaluations of compliance are planned. 
12.7 Interim Analyses 
No interim analyses are planned. 
12.8 Additional Statistical Considerations 
12.8.1 Analysis Populations 
Approximately 800 subjects at least 9 years of age and older with moderate or severe acne (a 
score of 3 or 4 [moderate to severe] on the EGSS scale) will be enrolled and randomized in the 
study. With a 1:1 randomization ratio, it is anticipated that: 
• 400 subjects will be randomized to receive IDP-123 Lotion, once-daily application 
• 400 subjects will be randomized to receive IDP-123 Vehicle Lotion, once-daily 
application 
The ITT population will consist of all randomized subjects who were dispensed study 
medication. The safety population will be comprised of all randomized subjects who are 


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presumed to have used the study medication at least once and who provide at least one post-
baseline safety evaluation. 
An intent-to-treat (ITT) analysis will be conducted on all study subjects. A per-protocol (PP) 
analysis will also be conducted. Subjects will be eligible for the PP analysis if they complete the 
12-week evaluation without noteworthy study protocol violations (i.e., any subject or 
investigator activity that could have possibly interfered with the therapeutic administration of the 
treatment or the precise evaluation of treatment efficacy). The PP population will include 
subjects in the safety population who do not meet any of the following criteria: 
• Failed any of the inclusion/exclusion criteria; 
• Have taken any interfering concomitant medications; 
• Did not attend the Week 12 visit; 
• Missed more than 1 post baseline study visit prior to Week 12 
• Have not been compliant with the dosing regimen (i.e., Subjects may not miss more 
than five consecutive days of dosing and must take 80-120% of expected doses. The 
number of expected doses will be determined for each subject based on the length of 
their participation in the study); 
• Out of visit window at the 12-week visit. 
Subjects that discontinue from the study due to an adverse event related to study treatment or 
documented lack of treatment effect will be included in the PP population. Prior to breaking the 
blind, other additional criteria may be added to the list to accommodate for unforeseen events 
that occurred during the conduct of the trial that result in noteworthy study protocol violations.  
The safety population will be comprised of all randomized subjects who are presumed to have 
used the study medication at least once and who provide at least one post-baseline safety 
evaluation.  
12.8.2 Sample Size Determination 
These power calculations are based primarily on the observed Week 12 results of the Phase 2 
study, V01-123A-201. This study was a four-arm trial including IDP-123 Lotion versus its 
Vehicle Lotion and cream and is therefore a relevant study for powering the current study.  
A sample size of 400 per treatment arm has greater than 99% power to detect a statistically 
significant difference in inflammatory lesions with a significance level of 0.05. The estimated 
absolute change from baseline in treatment means were 18.1 and 14.0 for IDP-123 Lotion versus 
its combined Vehicle, respectively, with a standard deviation of 8.75. 
A sample size of 400 per treatment arm has greater than 99% power to detect a statistically 
significant difference in non-inflammatory lesions with a significance level of 0.05 using the 
estimated absolute change from baseline in treatment means of 21.6 and 13.1 for IDP-123 Lotion 
versus its combined Vehicle, respectively, with a standard deviation of 14.0. 


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In order to achieve at least 90% power to detect a statistically significant difference in the 
proportion of subjects who have at least a 2 grade reduction at Week 12 from baseline in EGSS 
and were Clear or Almost Clear with a significance level of 0.05, a sample size of 400 per 
treatment group is required.  The estimated percentages with a 2 grade reduction at Week 12 
from baseline in the EGSS and Clear or Almost Clear are 18.8% and 10.1% for IDP-123 Lotion 
versus its Combined Vehicle respectively. 
12.8.3 Handling of Missing Data 
The method of multiple imputation will be used (see Section 12.1.9). 
12.8.4 Multicenter Issues 
The study will be conducted at multiple investigational centers in North America with the 
intention of pooling the results for analysis. Site specific data summaries, however, will be 
presented. 
12.8.5 Multiplicity Issues 
The overall Type I error will be controlled by requiring the three co-primary efficacy endpoints 
to be statistically significant. Specifically, failure of any one of the primary efficacy endpoints 
will invalidate the statistical significance of the secondary efficacy endpoints. See Section 12.1.6 
for further detail. 
12.8.6 Windowing Rules 
The timing of all study visits is relative to Baseline (Day 0). The Week 2, Week 4 and Week 8 
visits should occur within ± 3 days of the scheduled times, the Week 12 visit should occur within 
-3 / +5 days of the scheduled time. 
13 Quality Control and Quality Assurance 
13.1 Study Monitoring 
An Investigator Meeting and/or an initiation visit will be conducted with the principal 
investigator and study coordinators by sponsor and/or its designee. During this meeting, an 
extensive review and discussion of the protocol, the role of the study technician, all study 
procedures, source documents, and eCRFs will be conducted. Evaluation scales will be reviewed 
extensively and documentation of training will be recorded for training of sponsor-approved 
evaluators. 
The study monitors/clinical research associates will be trained prior to study initiation. Following 
this training, an overview of the study disease and study material background will be understood. 
Specific monitoring guidelines and procedures to be followed during monitoring visits will also 
be utilized. During the course of the study, all data will be 100% source document verified by the 
monitors. All subject source records must be made available to the monitors. 


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The conduct of the study will be closely monitored by the sponsor following GCP guidelines. 
The reports of these verifications will also be archived with the study report. In addition, 
inspections or on site audits may be carried out by local authorities or by the sponsor's Quality 
Assurance Department. The investigators will allow the sponsor's representatives and any 
regulatory agency to examine all study records, corresponding subject medical records, clinical 
dispensing records and storage area, and any other documents considered source documentation. 
The investigators agree to assist the representative, if required. 
13.2 Audits and Inspections 
The study will be conducted under the sponsorship of Valeant in conformation with all 
appropriate local and federal regulations, as well as ICH guidelines. Interim and end of study 
audits of raw data, study files, and final report may be conducted by Valeant’s Quality Assurance 
Department or designee. 
The sponsor is responsible for implementing and maintaining quality assurance and quality 
control systems to ensure that studies are conducted and data are generated, documented, and 
reported in compliance with the protocol, GCP, and applicable regulatory requirements. In 
addition, the sponsor will be responsible for securing agreement from all involved parties to 
ensure direct access to all study related investigational centers, source data/documents, eCRFs, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by 
domestic and foreign regulatory authorities. 
13.3 Data Quality Assurance 
All assessments performed will be accurately documented in the subject’s source documents and 
eCRFs. The investigator or designee will enter the information required by the protocol into the 
source documents and eCRFs provided by the sponsor or designee. Subjects will be identified in 
the eCRFs by their assigned subject number and initials only. 
The investigators must read the protocol thoroughly and must follow the instructions exactly. 
Any deviations should be agreed to by prior discussion between the sponsor and the investigator, 
with appropriate written protocol amendments made prior to implementing the agreed changes. 
Any amendment containing major modifications (particularly if it may involve an increased risk 
to the subjects) will be approved by the IRB/IEC before it may be implemented. No change in 
the conduct of the study can be instituted without written approval from the sponsor. 
14 Ethics and Administrative Issues 
14.1 Ethical Conduct of the Study 
This study will be conducted in accordance with the ethical principles originating from the 
Declaration of Helsinki, ICH guidelines, GCP, and in compliance with local regulatory 


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requirements. The investigator agrees, when signing the protocol, to adhere to the instructions 
and procedures described in it and thereby to adhere to the principles of GCP. 
14.2 Ethics Review 
This protocol, proposed informed consent form and other information to subjects, and all 
appropriate amendments will be properly reviewed and approved by an Institutional Review 
Board (IRB) or Independent Ethics Committee (IEC). A signed and dated notification of the 
IRB/IEC approval will be provided to the sponsor and investigator prior to study initiation. The 
name and occupation of the chairman and members of the IRB/IEC will be supplied to the 
Sponsor. The investigator will provide required progress reports and report all SAEs to the 
IRB/IEC as required by the IRB/IEC. 
14.3 Written Informed Consent 
Written informed consent/assent, in accordance with local clinical investigation regulations, must 
be obtained prior to participation in the study. The investigator or designee will discuss the 
purpose of the study with each subject, and provide a description of the study drug (including 
any potential and possible side effects) and the study procedures. Information must be given both 
in oral and written form. Subject information will be provided in a language understandable to 
the subject and may not include any language that appears to waive any of the subject‘s legal 
rights or appears to release the investigator, the sponsor or the institution from liability or 
negligence. 
The investigator will provide the prospective subject sufficient time to consider whether or not to 
participate, minimizing the possibility of coercion or undue influence and will discuss any 
questions the subject may have. The investigator will explain to the subject that participation in 
the study is voluntary and that withdrawal from the study is possible at any time without 
detriment to care. The consent must include acknowledgment that medical records and medical 
data derived from the study may be forwarded to the Sponsor or to responsible local or federal 
authorities. 
No subject can enter the study or have any study related procedures performed before his/her 
written informed consent has been obtained. The original signed and dated informed consent 
form will be retained with the study records, and a copy of the signed form will be given to the 
subject. 
An informed consent template will be supplied by the sponsor or designee. Any changes to the 
informed consent form must be agreed to by the Sponsor or designee prior to submission to the 
IRB/IEC, and a copy of the approved version must be provided to the sponsor or designee after 
IRB/IEC approval. 


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14.4 Subject Data Protection 
Subject data will be protected by ensuring that no captured data contain subject names, 
addresses, telephone numbers, email addresses, or other direct personally identifying 
information. It is acknowledged that subject initials, demographics (including birthdates), 
medical histories, and prior concomitant medication uses, along with the name and address of the 
enrolling investigator may allow for personal identification of study participants. Other than 
where necessary to meet regulatory requirements, all data collected in this study will be 
presented in tabulated (i.e., aggregate) form and listings containing information that could be 
used to identify an individual subject will not be included in any public disclosures of the study 
data or the study results. 
14.5 Data Monitoring Committee 
Not applicable. 
14.6 Financial Disclosure 
Financial disclosures will be obtained from all investigators in order to document any potential 
conflicts of interest. 
14.7 Investigator Obligations 
The investigator agrees, when signing the protocol, to adhere to the instructions and procedures 
described in it and thereby to adhere to the principles of Good Clinical Practice (GCP). 
14.8 Changes to the Protocol 
The investigators must read the protocol thoroughly and must follow the instructions exactly. 
Whenever possible, any planned deviations should be agreed to by prior discussion between the 
sponsor and the investigator, with appropriate documentation of Sponsor approval prior to 
effecting the changes agreed upon. Any amendment to the protocol containing major 
modifications (particularly if it may involve an increased risk to the subjects) will be approved 
by the IRB/IEC before it may be implemented. No change in the conduct of the study can be 
instituted without written approval from the Sponsor. 
14.9 Confidentiality/Publication of the Study 
All the data furnished to the investigator and his/her staff and all data obtained through this 
protocol will be regarded as confidential and proprietary in nature and will not be disclosed to 
any third party, except for the FDA or other regulatory body, without written consent from the 
Sponsor. 


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15 Data Handling and Record Keeping 
15.1 Inspection of Records 
Investigators must maintain detailed records on all study subjects who are enrolled in the study 
or undergo screening. Data will be recorded in the subject’s source documents and in applicable 
study logs provided by the Sponsor. Source documents include subject medical records, hospital 
charts, clinic charts, investigator subject study files, as well as the results of diagnostic tests 
(e.g., laboratory tests). All required data should be recorded in the study documentation 
completely for prompt data review. Upon study completion or at any other time specified by the 
Sponsor or designee, the appropriate study documents must be submitted. 
The investigator must keep accurate separate records (source documentation) of all subject visits, 
being sure to include all pertinent study related information. At a minimum, this includes the 
following information: 
• A statement indicating that the subject has been enrolled in the study and the subject 
number 
• Date that informed consent was obtained 
• Evidence that the subject meets study eligibility requirements (e.g., medical history, 
screening evaluations) 
• Dates of all study related visits and results of any evaluations/procedures performed, 
including who performed each assessment at each visit 
• Use of any concurrent medications / therapies during the study 
• Documentation of study drug accountability 
• Any and all side effects and AEs must be thoroughly documented to conclusion 
• Results of any diagnostic tests conducted during the study 
• The date the subject exited the study and a statement indicating that the subject 
completed the study or was discontinued early, including the reason for 
discontinuation 
Notes describing telephone conversations and all electronic mail with the subject or the sponsor 
(sponsor’s designee) concerning the study must be recorded or kept on file. All source 
documents must be made available to the sponsor and the sponsor’s designated monitor upon 
request. 


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15.2 Retention of Records 
The investigator should properly store and maintain all study records in accordance with sponsor 
directives. All records relating to the conduct of this study are to be retained by the investigator 
until notified by the Sponsor in writing that the records may be destroyed. 
The investigator will allow representatives of the Sponsor’s monitoring team, the governing 
IRB/IEC, the FDA, and other applicable regulatory agencies to inspect all study records, eCRFs, 
and corresponding portions of the subject’s clinic and/or hospital medical records at regular 
intervals throughout the study. These inspections are for the purpose of verifying adherence to 
the protocol, completeness and accuracy of the data being entered onto the eCRF, and 
compliance with FDA or other regulatory agency regulations. 
 
 


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16 References 
1. 
Leyden JJ, Shalita AR. Rational therapy for acne vulgaris: an update on topical treatment. 
J Am Acad Dermatol. 1986;15(4 Pt 2):907-15. 
2. 
Webster GF. Acne vulgaris. BMJ. 2002;325(7362):475-9. 
3. 
Eady EA. Bacterial resistance in acne. Dermatology. 1998;196(1):59-66. 
4. 
Eady EA, Farmery MR, Ross JI, Cove JH, Cunliffe WJ. Effects of benzoyl peroxide and 
erythromycin alone and in combination against antibiotic-sensitive and -resistant skin 
bacteria from acne patients. Br J Dermatol. 1994;131(3):331-6. 
5. 
Leyden JJ, McGinley KJ, Cavalieri S, Webster GF, Mills OH, Kligman AM. 
Propionibacterium acnes resistance to antibiotics in acne patients. J Am Acad Dermatol. 
1983;8(1):41-5. 
6. 
Shalita A. The integral role of topical and oral retinoids in the early treatment of acne. J 
Eur Acad Dermatol Venereol. 2001;15 Suppl 3:43-9. 
7. 
McLane J. Analysis of common side effects of isotretinoin. J Am Acad Dermatol. 
2001;45(5):S188-94. 
8. 
Orfanos CE, Ehlert R, Gollnick H. The retinoids. A review of their clinical pharmacology 
and therapeutic use. Drugs. 1987;34(4):459-503. 
9. 
Lucky AW, Cullen SI, Funicella T, Jarratt MT, Jones T, Reddick ME. Double-blind, 
vehicle-controlled, multicenter comparison of two 0.025% tretinoin creams in patients 
with acne vulgaris. J Am Acad Dermatol. 1998;38(4):S24-30. 
10. 
Zar, JH. Biostatistical analysis. 2nd Edition. Englewood Cliffs, NJ: Prentice-Hall. P. 118-
119. 1984. 


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17 Appendices 
17.1 Subject Instruction Sheet 
Wash your face gently with a mild cleanser approved by your study doctor and warm (not hot) 
water. Rinse thoroughly and gently pat dry with a cotton towel. Wait until skin is completely dry 
before applying the study drug. 
 
A thin layer of study drug should be applied once daily at home (in the evening) to the entire 
face for twelve weeks (up to evening prior to Week 12 visit). Study drug application time will 
vary on days of scheduled clinic visits (Baseline, Weeks 2, 4 and 8) – reminder: do NOT apply 
study drug prior to on-site study visits.   
 
Use the tube to dispense a pea-sized amount of study drug to your fingertip.  This dose should 
then be dotted on to 6 areas (chin, left cheek, right cheek, nose, left forehead, right forehead) on 
the face. After distributing the dose in this manner, gently rub the lotion into the skin. This 
amount should be used to evenly cover the entire face excluding the mouth, eyes and lips. It is 
important to treat your entire face.  
 
Do NOT treat only specific lesions. DO NOT APPLY MORE THAN THE PRESCRIBED 
AMOUNT.  
 
Be sure to wash your hands after you apply the product. 
 
Reminders: 
- 
On study visit days (Weeks 2, 4, 8 and 12) bring your study drug with you. 
- 
On study visit days (Baseline, Weeks 2, 4, and 8) please wait until after your study visit 
assessments are completed to apply the study drug at the investigational site. 
- 
On study visit days (Baseline, Weeks 2, 4, and 8) since study drug is applied at the 
investigational site, please do not re-apply again in the evening. 
- 
Last dose of study drug is applied on the evening prior to Week 12 visit. 
- 
Avoid contact with the eyes, inside the nose, mouth and all mucous membranes. If contact 
with eyes occurs, rinse thoroughly with water. 
- 
Do not cover the affected areas with any type of dressing, such as gauze. 
- 
THE STUDY DRUG SHOULD BE USED ONLY BY THE PERSON FOR WHOM IT 
WAS PRESCRIBED and it should be kept out of the reach of others of limited capacity to 
read or understand. 
- 
Store at controlled room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted 
between 15°C to 30°C (59°F to 86°F). Do not refrigerate or freeze. Avoid excessive heat or 
cold. 


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- 
Tubes of study drug must be returned to the study facility, even if they are empty. 
- 
If you miss any doses, at your next visit inform the study doctor of the date(s) of the missed 
dose(s). 
- 
Continue to use the same, study doctor approved, cleanser, moisturizer and sunscreen 
throughout the study.  
- 
You must not use any other treatment for your facial acne while you are participating in this 
study. 
- 
Avoid unnecessary sun exposure and tanning booths.  Use Investigator-approved sunscreen 
with at least SPF 15 and wear protective clothing during the day (e.g., hat) if you have to be 
in the sunlight. 
- 
It is important that you inform the study site about any medications (i.e., prescriptions, over-
the-counter medications, street drugs, or herbal medications) that you have taken during the 
study. 
 
If you have any questions or have a potential research-related side effect or injury you may 
contact ________________________ at _________________. 
 
 
 
 


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17.2 Cleansers, Moisturizers and Sunscreen Use Guidelines 
Subjects may use the following products as examples of approved products. The Investigator 
may use his/her discretion on what products each subject may use in the treatment area during 
the study.  Subjects may use the below set of examples or other Investigator approved non-
medicated products on the treatment area. Information regarding products used should be 
captured in the source document and recorded on the eCRF. 
 
Approved Cleanser Examples: 
• CeraVe cleanser 
• Cetaphil daily cleaner and gentle cleansing bar 
• Purpose gentle cleansing wash 
 
Approved Moisturizer Examples: 
• CeraVe Cream or Lotion 
• Moisturel cream or lotion 
• Nutraderm 
• Cetaphil lotion or cream 
• DML 
• Eucerin lotion or cream 
• Purpose 
 
Approved Moisturizer/Sunscreen Combination Product Examples: 
• CeraVe Lotion A.M. 
• Olay Complete (SPF 15) 
• Neutrogena Health Defense Daily Moisturizer (SPF 30) 
• Cetaphil Daily Facial Moisturizer (SPF 15) 
 
Approved Sunscreen Examples: 
• Banana Boat Sport Sunblock Lotion (SPF 15, 30+ or 50) 
• Neutrogena UVA/UVB (SPF 30 or 45) 
• Neutrogena Sensitive Skin Sunblock Lotion (SPF 17) 
• Neutrogena Healthy Defense Oil-Free Sunblock Lotion (SPF 30 or 45) 
• Coppertone Water Babies UVA/UVB Sunblock Lotion (SPF 45) 
 
 


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