CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`207154Orig1s000
`
`MEDICAL REVIEW(S)
`
`
`
`
`
`
`
`
`

`

`CLINICAL REVIEW
`
`Application Type NDA
`Application Number(s) 207154
`Priority or Standard Standard
`
`Submit Date(s) April 28, 2015
`Received Date(s) April 28, 2015
`PDUFA Goal Date February 28, 2016
`Division / Office DDDP/ODEIII
`
`Reviewer Name(s) Patricia C. Brown, MD
`Review Completion Date January 20, 2016
`
`Established Name Dapsone gel, 7.5%
`(Proposed) Trade Name ACZONE® Gel, 7.5%
`Therapeutic Class Acne agent
`Applicant Allergan, Inc.
`
`Formulation(s) Gel
`Dosing Regimen Once daily
`Indication(s) Topical treatment of acne
`vulgaris
`Intended Population(s) Patients 12 years of age and
`older
`
`Template Version: March 6, 2009
`
`Reference ID: 3875816
`
`

`

`Clinical Review
`Patricia C. Brown, MD
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%
`
`2
`
`Table of Contents
`1 RECOMMENDATIONS/RISK BENEFIT ASSESSMENT..........................................8
`1.1 Recommendation on Regulatory Action ..............................................................8
`1.2 Risk Benefit Assessment .....................................................................................8
`1.3 Recommendations for Postmarket Risk Evaluation and Mitigation Strategies ..10
`1.4 Recommendations for Postmarket Requirements and Commitments...............10
`INTRODUCTION AND REGULATORY BACKGROUND .......................................11
`2.1 Product Information ...........................................................................................11
`2.2 Tables of Currently Available Treatments for Proposed Indications..................12
`2.3 Availability of Proposed Active Ingredient in the United States .........................15
`2.4
`Important Safety Issues with Consideration to Related Drugs ..........................15
`2.5 Summary of Presubmission Regulatory Activity Related to Submission ...........16
`2.6 Other Relevant Background Information ...........................................................18
`3 ETHICS AND GOOD CLINICAL PRACTICES........................................................18
`3.1 Submission Quality and Integrity .......................................................................18
`3.2 Compliance with Good Clinical Practices ..........................................................21
`3.3 Financial Disclosures.........................................................................................21
`4 SIGNIFICANT EFFICACY/SAFETY ISSUES RELATED TO OTHER REVIEW
`DISCIPLINES...........................................................................................................24
`4.1 Chemistry Manufacturing and Controls .............................................................24
`4.2 Clinical Microbiology ..........................................................................................27
`4.3 Preclinical Pharmacology/Toxicology ................................................................27
`4.4 Clinical Pharmacology .......................................................................................30
`4.4.1 Mechanism of Action...................................................................................30
`4.4.2 Pharmacodynamics.....................................................................................30
`4.4.3 Pharmacokinetics........................................................................................30
`5 SOURCES OF CLINICAL DATA.............................................................................35
`5.1 Tables of Studies/Clinical Trials.........................................................................35
`5.2 Review Strategy.................................................................................................36
`5.3 Discussion of Individual Studies/Clinical Trials..................................................37
`6 REVIEW OF EFFICACY ..........................................................................................46
`Efficacy Summary .......................................................................................................46
`6.1
`Indication ...........................................................................................................47
`6.1.1 Methods.......................................................................................................47
`6.1.2 Demographics .............................................................................................48
`6.1.3 Subject Disposition......................................................................................49
`6.1.4 Analysis of Primary Endpoint(s) ..................................................................50
`6.1.5 Analysis of Secondary Endpoints(s)............................................................51
`
`Reference ID: 3875816
`
`2
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`

`

`Clinical Review
`Patricia C. Brown, MD
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%
`
`6.1.6 Other Endpoints ..........................................................................................51
`6.1.7 Subpopulations............................................................................................52
`6.1.8 Analysis of Clinical Information Relevant to Dosing Recommendations.....53
`6.1.9 Discussion of Persistence of Efficacy and/or Tolerance Effects .................53
`6.1.10 Additional Efficacy Issues/Analyses............................................................53
`7 REVIEW OF SAFETY..............................................................................................54
`Safety Summary..........................................................................................................54
`7.1 Methods .............................................................................................................58
`7.1.1 Studies/Clinical Trials Used to Evaluate Safety ..........................................58
`7.1.2 Categorization of Adverse Events...............................................................60
`7.1.3 Pooling of Data across Studies/Clinical Trials to Estimate and Compare
`Incidence.....................................................................................................60
`7.2 Adequacy of Safety Assessments .....................................................................61
`7.2.1 Overall Exposure at Appropriate Doses/Durations and Demographics of
`Target Populations ......................................................................................61
`7.2.2 Explorations for Dose Response.................................................................64
`7.2.3 Special Animal and/or In Vitro Testing ........................................................64
`7.2.4 Routine Clinical Testing...............................................................................64
`7.2.5 Metabolic, Clearance, and Interaction Workup ...........................................64
`7.2.6 Evaluation for Potential Adverse Events for Similar Drugs in Drug Class...64
`7.3 Major Safety Results..........................................................................................64
`7.3.1 Deaths.........................................................................................................64
`7.3.2 Nonfatal Serious Adverse Events................................................................65
`7.3.3 Dropouts and/or Discontinuations ...............................................................69
`7.3.4 Significant Adverse Events..........................................................................77
`7.3.5 Submission Specific Primary Safety Concerns ...........................................78
`7.4 Supportive Safety Results .................................................................................79
`7.4.1 Common Adverse Events............................................................................79
`7.4.2
`Laboratory Findings.....................................................................................83
`7.4.3 Vital Signs ...................................................................................................86
`7.4.4 Electrocardiograms (ECGs) ........................................................................87
`7.4.5 Special Safety Studies/Clinical Trials..........................................................89
`7.4.6
`Immunogenicity .........................................................................................110
`7.5 Other Safety Explorations................................................................................110
`7.5.1 Dose Dependency for Adverse Events .....................................................110
`7.5.2 Time Dependency for Adverse Events......................................................112
`7.5.3 Drug-Demographic Interactions ................................................................112
`7.5.4 Drug-Disease Interactions.........................................................................117
`7.5.5 Drug-Drug Interactions..............................................................................117
`7.6 Additional Safety Evaluations ..........................................................................117
`7.6.1 Human Carcinogenicity .............................................................................117
`7.6.2 Human Reproduction and Pregnancy Data...............................................118
`7.6.3 Pediatrics and Assessment of Effects on Growth .....................................121
`
`Reference ID: 3875816
`
`3
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`

`

`Clinical Review
`Patricia C. Brown, MD
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%
`
`7.6.4 Overdose, Drug Abuse Potential, Withdrawal and Rebound ....................123
`7.7 Additional Submissions / Safety Issues ...........................................................123
`8 POSTMARKET EXPERIENCE..............................................................................124
`9 APPENDICES........................................................................................................125
`9.1
`Literature Review/References .........................................................................125
`9.2
`Labeling Recommendations ............................................................................125
`9.3 Advisory Committee Meeting...........................................................................125
`
`Reference ID: 3875816
`
`4
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`

`

`Clinical Review
`Patricia C. Brown, MD
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%
`
`Table of Tables
`
`Table 1: ACZONE Packaging Configurations................................................................11
`Table 2: Topical Acne Products (Acne Vulgaris) – Single Active ...................................12
`Table 3: Topical Acne Products (Acne Vulgaris) – Combination....................................13
`Table 4: Oral Acne Products..........................................................................................14
`Table 5: Co-Primary Efficacy Results at Week 12 for All Centers and Centers with
`Financial Disclosures Removed (MI, ITT) .......................................................23
`Table 6: Composition of ACZONE (dapsone) Gel, 7.5%...............................................25
`Table 7: Summary of Plasma Dapsone PK Parameters ...............................................31
`Table 8: Top 25 Sites - Trial 006 by Sample Size ..........................................................38
`Table 9: Top 25 Sites - Trial 007 by Sample Size ..........................................................39
`Table 10: Flow Chart – Trials 225678-006 & 007..........................................................42
`Table 11: Global Acne Assessment Score ....................................................................43
`Table 12: Trials Used to Evaluate Efficacy.....................................................................47
`Table 13: Demographics ITT Population .......................................................................48
`Table 14: Baseline Disease Characteristics ITT Population..........................................49
`Table 15: Disposition of Subjects ITT Population...........................................................49
`Table 16: Results for the Co-Primary Efficacy Endpoints at Week 12 (MI, ITT)............50
`Table 17: Results for the Secondary Efficacy Endpoints (Based on Lesion Counts) at
`Week 12 (MI(1), ITT) ........................................................................................51
`Table 18: Co-Primary Efficacy Results at Week 12 by Gender, Race, Age, and Country
`for Trial 006 (MI, ITT) ......................................................................................52
`Table 19: Co-Primary Efficacy Results at Week 12 by Gender, Race, Age, and Country
`for Trial 007 (MI, ITT) ......................................................................................53
`Table 20: Subjects Exposed in Pooled Safety Trials......................................................61
`Table 21: Treatment Duration (days) Pooled Safety Trials ...........................................61
`Table 22: Total Amount of Study Drug Used (Pooled Safety Trials) ..............................62
`Table 23: Average Daily Use of Study Drug (Pooled Safety Trials) ...............................62
`Table 24: Demographic Characteristics (Pooled Safety Trials).....................................63
`Table 25: Serious Treatment-Emergent Adverse Events (Pooled Safety Trials) ..........66
`Table 26: Treatment Emergent Adverse Events Leading to Study Discontinuation
`(Pooled Safety Trials)......................................................................................70
`Table 27: Overview of Adverse Events – TEAEs (Pooled Safety Trials).......................79
`Table 28: Most Common TEAEs (Pooled Safety Trials)................................................80
`Table 29: Application Site TEAEs (Pooled Safety Trials) Occurring in at Least 1 Subject
`in ACZONE Gel, 7.5% Group..........................................................................80
`Table 30: Treatment Related TEAEs (Pooled Safety Trials) .........................................81
`Table 31: Local Cutaneous Irritation by Maximum Severity in Subjects with Acne
`Vulgaris Whose Irritation Score was Higher than at Baseline.........................83
`Table 32: Methemoglobin – Baseline and Change from Baseline (Trial 004) ...............85
`Table 33: Scoring of Dermal Response.........................................................................91
`Table 34: Scoring of Other Effects..................................................................................91
`Table 35: Sensitization Reaction Scoring.......................................................................92
`
`Reference ID: 3875816
`
`5
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`

`Clinical Review
`Patricia C. Brown, MD
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%
`
`Table 36: Mean Cumulative Irritancy Index during Induction (Subset 1 PP Population)
`........................................................................................................................93
`Table 37: Frequency of Worst Combined Score Post-Baseline during Induction (Subset
`1 PP Population) .............................................................................................94
`Table 38: Frequency of Worst Combined Score Post-Baseline during Induction (Subset
`2 – PP Population) ..........................................................................................96
`Table 39: Incidence of Sensitization (Subsets 1&2 – PP Population) ...........................98
`Table 40: Summary of Subjects Rechallenged .............................................................98
`Table 41: Response Grading.......................................................................................102
`Table 42: Effects on Superficial Layers of Skin ...........................................................102
`Table 43: Response Grading.......................................................................................105
`Table 44: Effects on Superficial Layers of Skin ...........................................................106
`Table 45: Photosensitization Reaction Scoring ............................................................107
`Table 46: Overview of Adverse Events Reported by Amount of Product Used (Pooled
`Trials; Safety Population) ..............................................................................110
`Table 47: Treatment-Related(1) Treatment-Emergent Adverse Events by Amount of
`Product Used (Pooled Trials, Safety Population)..........................................111
`Table 48: Treatment Emergent Adverse Events, Primary SOC by Age Group (Pooled
`Safety Trials) .................................................................................................112
`Table 49: Treatment Emergent Adverse Events, Primary SOC by Gender (Pooled
`Safety Trials) .................................................................................................114
`Table 50: Treatment Emergent Adverse Events, Primary SOC by Race (Pooled Safety
`Trials) ............................................................................................................116
`
`Reference ID: 3875816
`
`6
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`

`

`Clinical Review
`Patricia C. Brown, MD
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%
`
`Table of Figures
`
`Figure 1: Induction Irritation Scores for Subset 1 (Cumulative Irritation) PP Population
`........................................................................................................................95
`Figure 2: Induction Irritation Scores (Subset 2 RIPT – PP Population) ..........................97
`
`Reference ID: 3875816
`
`7
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`

`

`Clinical Review
`Patricia C. Brown, MD
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%
`
`1 Recommendations/Risk Benefit Assessment
`
`1.1 Recommendation on Regulatory Action
`
`This reviewer recommends an approval action for the current NDA 207154, ACZONE ®
`(dapsone) Gel, 7.5% for the topical treatment of acne vulgaris in patients 12 years of
`age and older.
`
`1.2 Risk Benefit Assessment
`
`The applicant, Allergan, Inc., has submitted a 505(b)1 New Drug Application for
`ACZONE ® (dapsone) Gel, 7.5%. The drug product proposed in this application is a
`topical gel formulation containing 7.5% dapsone and intended for once daily application.
`ACZONE® (dapsone) Gel, 5% was approved July 7, 2005 (NDA 21794) and is currently
`marketed in the US for twice daily topical treatment of acne vulgaris.
`
`To demonstrate efficacy, the applicant submitted data from two identically designed
`Phase 3 pivotal trials, trial 225678-006 and 225678-007 (Trials 006 and 007). These
`were multicenter, double-blind, randomized, parallel-group, vehicle-controlled, 12-week
`trials. Trials 006 and 007 were conducted in 96 and 93 US centers and 9 and 10
`Canadian centers, respectively. To enroll in these trials, subjects must have been 12
`years of age or older and had a Global Acne Assessment Score (GAAS) of 3
`(moderate). They also must have had 20-50 inflammatory lesions (papules and
`pustules) and 30-100 non-inflammatory lesions (open comedones and closed
`comedones) on the face. Subjects applied study product to their entire face once daily
`for 12 weeks. Subjects also topically administered the study product once daily to acne-
`affected areas within reach on the neck, shoulders, upper back, and/or upper chest. The
`latter areas were not considered in the analysis of efficacy; however, they were
`considered in the analysis of safety for the pivotal trials.
`
`In both pivotal trials the protocol specified co-primary efficacy endpoints included the
`proportion of subjects achieving a score of 0 (none) or 1 (minimal) on the GAAS at
`Week 12 and the absolute change in inflammatory and non-inflammatory lesion counts
`from baseline to Week 12. In both trials 006 and 007, ACZONE Gel, 7.5% was
`statistically superior (p-values ≤ 0.004) to vehicle gel on all three co-primary efficacy
`endpoints.
`
`For the secondary endpoints which included, percent change in inflammatory and non-
`inflammatory lesion counts from baseline to Week 12, ACZONE Gel, 7.5% was
`statistically superior (p-values ≤ 0.001) to vehicle gel in both trials.
`
`Reference ID: 3875816
`
`8
`
`

`

`Clinical Review
`Patricia C. Brown, MD
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%
`
`The principal evaluation of safety for ACZONE ® (dapsone) Gel, 7.5%, for the indication
`of topical treatment of acne vulgaris in patients 12 years of age and older, was based on
`trials that included subjects treating acne vulgaris on the face once daily for 12 weeks.
`The trials in the pooled safety database include trial 225678-006 (pivotal Phase 3, 2-
`arm vehicle controlled) and trial 225678-007 (pivotal Phase 3, 2-arm vehicle controlled).
`Additional safety information is available from the four trials; 225678-004
`pharmacokinetic (PK, Phase 1, 4-arm, active controlled), 225678-009 dermal safety
`(Phase 1, RIPT sensitization), 225678-010 dermal safety (Phase 1, phototoxicity), and
`225678-011 dermal safety (Phase 1, photoallergy). All of the trials were conducted with
`the final-to-be-marketed formulation. (Trial 225678-004, pharmacokinetic, included one
`arm with the final-to-be-marketed formulation.)
`
`No deaths were reported in any of the six clinical trials. For the pooled trials, in the
`ACZONE Gel, 7.5% group, 7 of 2175 subjects (0.3%) had a total of 8 serious treatment
`emergent adverse events (TEAEs). These were application site dermatitis (33 days
`after treatment), appendicitis (46 days after treatment), tibia fracture 34 days after
`treatment), acute myeloid leukemia (42 days after treatment), helicobacter pylori
`infection (19 days after treatment), appendicitis, peritoneal hematoma (50 and 53 days,
`respectively after treatment), and alcoholism (28 days after treatment). The 8 serious
`TEAEs were considered not related to treatment with ACZONE Gel, 7.5%.
`
`For the pooled trials, in the vehicle group: 9 of 2175 subjects (0.4%) had a total of 9
`serious TEAEs. These were induced abortion (85 days after treatment), lumbar
`vertebral fracture (62 days after treatment), affective disorder (56 days after treatment),
`depression (75 days after treatment), anxiety (36 days after treatment), spontaneous
`pneumothorax (36 days after treatment), appendicitis (62 days after treatment),
`spontaneous abortion (16 days after treatment) and suicidal ideation (16 days after
`treatment). One serious TEAE, depression, was considered related to study medication
`(in this case vehicle).
`
`For the pivotal trials, in the ACZONE gel, 7.5% group, 6 of 2161 subjects (0.3%) had
`adverse events (TEAEs) leading to discontinuation. Of the TEAEs that led to
`discontinuation in subjects in the ACZONE group, 7 that occurred in 3 subjects were
`considered to be treatment related by the investigator. These events included
`application site acne and application site dermatitis in 1 subject; application site
`vesicles, application site swelling, application site pruritus, and pruritus in 1 subject; and
`application site discomfort (described as mild in severity) in 1 subject.
`
`For the pivotal trials, in the vehicle group: 7 of 2175 subjects (0.3%) had adverse
`events (TEAEs) leading to discontinuation. Of the TEAEs that led to discontinuation in
`patients in the vehicle group, 3 TEAEs that occurred in 3 subjects in the vehicle group
`were considered to be treatment related by the investigator. These events included
`application site pain (described as mild in severity) in 2 subjects and application site
`acne (described as severe) in 1 subject.
`
`Reference ID: 3875816
`
`9
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`

`

`Clinical Review
`Patricia C. Brown, MD
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%
`
`Treatment-related TEAEs, or adverse drug reactions, were reported in 3.5% (75/2161)
`of subjects in the ACZONE Gel, 7.5% group and 3.4% (73/2175) of patients in the
`vehicle group. The most common treatment related TEAEs (i.e., those occurring in ≥
`0.9% of subjects and at a rate greater than vehicle) were application site events:
`application site dryness (1.1% in the ACZONE Gel, 7.5% group versus 1.0% in the
`vehicle group) and application site pruritus (0.9% versus 0.5%).
`
`Regarding pediatric use, safety was evaluated in 1066 pediatric subjects 12 to 17 years
`of age treated with ACZONE Gel, 7.5%. Within this age subgroup, the safety profile, in
`terms of TEAEs, for ACZONE Gel, 7.5 % was similar to that of the vehicle control. In
`addition, the frequency of TEAEs was similar among those aged 12 to 17 years of age
`as compared with subjects > 18 years of age.
`
`Three dermal safety trials were performed in support of this application; 225678-009
`(RIPT sensitization), 225678-010 (phototoxicity), and 225678-011 (photoallergy). Under
`the conditions of the trials performed, ACZONE Gel, 7.5% and its vehicle did not show
`potential for sensitization and are unlikely to cause clinically meaningful irritation under
`normal use conditions. ACZONE Gel, 7.5% and its vehicle also did not show potential
`for phototoxicity in and did not show clinically significant potential for photoallergy in
`healthy subjects.
`
`For this 505(b)(1) application, based on the data submitted from the six trials in the
`clinical development program, safety and efficacy of ACZONE ® (dapsone) Gel, 7.5%
`have been established for the topical treatment of acne vulgaris in patients 12 years of
`age and older.
`
`1.3 Recommendations for Postmarket Risk Evaluation and Mitigation
`Strategies
`
`At this time, a postmarketing Risk Evaluation and Mitigation Strategy (REMS) is not
`recommended.
`
`1.4 Recommendations for Postmarket Requirements and Commitments
`
`Postmarket Requirement:
`For pediatric patients age 9 to 1 years and 11 months, information is needed about
`systemic exposure and safety after exposure to ACZONE® Gel, 7.5% applied to acne
`vulgaris. Deferred pediatric studies in pediatric patients age 9 to 11 years 11 months will
`be conducted as required by PREA.
`
`A proposal for the PMR is as follows:
`Conduct an open-label study to assess safety, pharmacokinetics, and treatment
`effect of ACZONE® Gel, 7.5% in 100 pediatric subjects age 9 to 11 years 11
`
`Reference ID: 3875816
`
`10
`
`

`

`Clinical Review
`
`Patricia C. Brown, MD
`NDA 207154
`
`ACZONE® (dapsone) Gel, 7.5%
`
`months with acne vulgaris. Pharmacokinetic assessments will be done in at least
`16 evaluable subjects under maximal use conditions.
`
`2 Introduction and Regulatory Background
`
`2.1 Product Information
`
`The applicant, Allergan, Inc., has submitted a 505(b)1 New Drug Application for
`ACZONE ® (dapsone) Gel, 7.5%. The objective of the current NDA is to provide data to
`support approval for the marketing of ACZONE® Gel for the topical treatment of acne
`vulgaris in patients 12 years of age and older.
`
`The drug product proposed in this application comprises a topical gel formulation
`containing 7.5% dapsone. ACZONE®(dapsone) Gel, 5% has been shown to be an
`effective treatment for acne with twice daily dosing. Allergan is developing a 7.5%
`dapsone formulation for once daily dosing. A|| excipients used in the formulation are
`listed on the FDA Inactive Ingredient Database and are in FDA-approved topical
`products.
`
`ACZONE® (dapsone) Gel, 7.5% is an off-white to yellow gel with suspended dapsone
`particles. It comprises
`"M", diethylene glycol
`monoethylether (DGME) as a
`“m, and methy'lparaben (MP) as a
`The drug product is packaged in an airless pump
`"4’. The airless pump
`of a bottle and pump actuator assembly.
`
`(5) (4)
`
`am consists
`
`The applicant has proposed that ACZONE®(dapsone) Gel, 7.5% be presented in "M"
`packaging configurations which are described in the following table:
`
`Table 1: ACZONE Packaging Configurations
`
`m
`
`
`
`
`
`
`
`1 bottle per
`(b) (4)
`
`90 g pump container
`
`
`
`90 g in 90 mL bottle
`
`Source: Applicant’s NDA, Module 3, 3.2.P.7, p. 2.
`
`Reference ID: 3875816
`
`1 1
`
`

`

`Clinical Review
`Patricia C. Brown, MD
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%
`
`The applicant proposed indication is “topical treatment of acne vulgaris in patients 12
`years of age and older.”
`
`Proprietary Name:
`The Division of Medication Error Prevention and Analysis, Office of Medication Error
`Prevention and Risk, reviewed the proposed proprietary name, Aczone, and concluded
`that it is conditionally acceptable. This was communicated to the applicant in a letter
`dated July 7, 2015. The applicant’s request for review of the proprietary name was
`dated April 28, 2015.
`
`2.2 Tables of Currently Available Treatments for Proposed Indications
`
`A number of topical and systemic drugs are available for the treatment of acne vulgaris.
`Approved therapies for acne vulgaris include oral and topical antibiotics and
`antimicrobials (e.g. erythromycin, clindamycin, benzoyl peroxide) systemic hormonal
`therapies (e.g. ethinyl estradiol/norgestimate) and topical retinoids (e.g. tretinoin,
`tazarotene). The oral formulation of isotretinoin is also available for severe, recalcitrant,
`nodulo-cystic acne.
`
`Table 2: Topical Acne Products (Acne Vulgaris) – Single Active
`Generic Name
`Brand Name
`Formulations
`Applicant/Owner
`Topical
`Antimicrobials
`Clindamycin
`phosphate
`
`Cleocin T
`
`Clindagel
`Evoclin
`
`Erygel
`Klaron
`
`Erythromycin
`Sulfacetamide
`sodium
`Retinoids
`
`tretinoin
`
`Retin-A
`
`Retin-A Micro
`Atralin
`Avita
`generic
`
`Solution 1%, lotion
`1%, gel 1%
`Gel 1%
`Foam 1%
`
`Pharmacia & Upjohn
`Precision
`Dermatology
`Delcor Asset
`
`Gel 2%
`Lotion, 10%
`
`Delcor Asset Corp
`Valeant
`
`Solution .05%, cream
`0.1% & .05% &
`0.025%, gel 0.025% &
`0.01%,
`Gel 0.1%, 0.04%,
`0.08%
`Gel 0.05%
`Gel 0.025%
`Cream 0.1%,
`0.05%,0.025%;gel
`
`Valeant
`
`Valeant
`Dow Pharm
`Mylan
`Matawan Pharms
`
`Reference ID: 3875816
`
`12
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`

`

`Clinical Review
`Patricia C. Brown, MD
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%
`
`Generic Name
`
`Brand Name
`
`adapaline
`
`Differin
`
`generic
`
`tazarotene
`
`Tazorac
`
`Formulations
`0.025%, 0.01%
`Cream 0.05%
`Cream 0.0375%,
`0.075%
`Gel 0.1%, 0.04%,
`0.05%
`Gel 0.1%, 0.3%;
`cream 0.1%, lotion
`0.1%
`Fougera Pharms
`Cream 0.1%
`Pliva Hrvatksa Doo
`Gel 0.1%
`Glenmark Generics
`Gel 0.1%
`Tolmar
`Gel 0.3%
`Actavis Mid Atlantic
`Gel 0.3%
`Allergan
`Cream 0.1%, 0.05%
`Allergan
`Gel 0.1%, 0.05%
`Stieffel Labs, Inc
`Aerosol, foam, 0.1%
`Fabior
`Compiled by reviewer from website “Drugs at FDA” accessed October 28, 2015
`
`Applicant/Owner
`
`Suneva
`Watson labs Inc
`
`Spear Pharms Inc
`
`Galderma Labs LP
`
`Table 3: Topical Acne Products (Acne Vulgaris) – Combination
`Generic Name
`Brand Name
`Formula-
`tions
`
`Combination Products
`Adapalene 0.1 %; benzoyl peroxide 2.5% Epiduo
`Adapalene 0.3 %; benzoyl peroxide 2.5% Epiduo Forte
`Adapalene 0.1 %; benzoyl peroxide 2.5% generic
`Benzoyl peroxide 2.5%; clindamycin
`Acanya
`phosphate 1.2%
`Benzoyl peroxide 3.75%; clindamycin
`phosphate 1.2%
`Benzoyl peroxide 5%; clindamycin
`phosphate 1%
`Benzoyl peroxide 5%; clindamycin
`phosphate 1.2%
`Benzoyl peroxide 5%; clindamycin
`phosphate 1%
`Benzoyl peroxide 5%; clindamycin
`phosphate 1.2%
`Benzoyl peroxide 5%; clindamycin
`phosphate 1%
`Benzoyl peroxide 5%; clindamycin
`phosphate 1%
`Benzoyl peroxide 5%; erythromycin 3%
`Benzoyl peroxide 5%; erythromycin 3%
`
`Onexton
`
`Benzaclin
`
`Duac
`
`generic
`
`generic
`
`generic
`
`generic
`Benzamycin
`Benzamycin
`
`Applicant/Owner
`
`Galderma Labs LP
`Galderma Labs LP
`Actavis Mid Atlantic
`Dow Pharm
`
`Dow Pharm
`
`Valeant
`
`Stiefel
`
`gel
`gel
`gel
`gel
`
`gel
`
`gel
`
`gel
`
`gel
`
`Mylan Pharms Inc
`
`gel
`
`gel
`
`gel
`gel
`gel
`
`Perrigo Israel
`
`Perrigo Israel
`
`Actavis Labs Ut Inc
`Valeant Intl
`Valeant Luxemborg
`
`Reference ID: 3875816
`
`13
`
`

`

`Clinical Review
`Patricia C. Brown, MD
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%
`
`Generic Name
`
`Brand Name
`
`Formula-
`tions
`
`Applicant/Owner
`
`Benzoyl peroxide 5%; erythromycin 3%
`Benzoyl peroxide 5%; erythromycin 3%
`Clindamycin phosphate 1.2%; tretinoin
`.025%
`Clindamycin phosphate 1.2%; tretinoin
`Medicis
`Gel
`Ziana
`.025%
`Compiled by reviewer from website “Drugs at FDA” accessed October 28, 2015
`
`gel
`gel
`Gel
`
`Tolmar
`Lyne
`Stiefel GSK
`
`Pak
`generic
`generic
`Veltin
`
`Formulations
`
`Applicant/
`Owner
`
`Indication
`
`Medicis
`
`Only inflammatory
`lesions of non-
`nodular moderate to
`severe acne vulgaris
`in patients 12 years
`of age and older.
`Mayne pharma Adjunctive therapy in
`severe acne
`In severe acne may
`be useful adjunctive
`therapy
`In severe acne may
`be useful adjunctive
`therapy
`Severe recalcitrant
`nodular acne in
`patients 12 years of
`age and older
`Severe recalcitrant
`nodular acne
`Severe recalcitrant
`nodular acne
`Moderate acne for
`women at least 14
`years old only if
`patient desires an
`oral contraceptive for
`birth control
`
`Aqua Pharms
`
`Heritage
`Pharms Inc
`
`Ranabxy
`
`Mylan Pharms
`Inc.
`Teva Pharms
`USA
`
`Bayer
`Healthcare
`
`Table 4: Oral Acne Products
`Generic Name
`Brand Name
`
`Oral
`Antibiotics
`
`Minocycline HCl
`
`Solodyn
`
`Doxycycline
`hyclate
`
`Doxycycline
`Monohydrate
`
`Tetracycline
`Hydrochloride
`
`Doryx
`
`Monodox
`
`Achromycin V
`
`Isotretinoin
`
`Absorica
`
`Extended release
`tablets 55mg, 65
`mg, 105 mg, 115
`m