`
` CENTER FOR DRUG EVALUATION AND
`
`
`
` RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`213433Orig1s000
`
`
`MULTI-DISCIPLINE REVIEW
`
`Summary Review
`Clinical Review
`Non-Clinical Review
`Statistical Review
`Clinical Pharmacology Review
`
`

`

`NDA/BLA Multidisciplinary Review and Evaluation: NDA 213433
`WINLEVI (clascoterone) cream, 1%
`NDA Multidisciplinary Review and Evaluation
`Application Type NME- In “The Program”
`Application Number(s) NDA 213433
`Priority or Standard Standard
`Submit Date(s) August 19, 2019
`Received Date(s) August 27, 2019
`PDUFA Goal Date August 27, 2020
`Division/Office Shari Targum, Deputy Director, Division of Dermatology and
`Dentistry
`Julie Beitz, Director Office of Immunology and Inflammation
`
`Review Completion Date
`Established/Proper Name Clascoterone cream, 1%
`(Proposed) Trade Name WINLEVI
`Pharmacologic Class NME
`Code Name N/A
`Applicant Cassiopea SpA
`Dosage Form Topical cream
`Applicant proposed Dosing
`Apply a thin layer (approximately 1 gram) to affected area
`Regimen
`twice daily (morning and evening)
`Applicant Proposed
`For the treatment of acne vulgaris in patients 9 years of age
`Indication(s)/Population(s)
`and older
`Applicant Proposed
`SNOMED CT Indication
`Disease Term for Each
`Proposed Indication
`Recommendation on
`Regulatory Action Approval
`Recommended
`For the treatment of acne vulgaris in patients 12 years of age
`Indication(s)/Population(s)
`and older
`(if applicable)
`Recommended SNOMED
`CT Indication Disease
`Term for Each Indication
`(if applicable)
`Recommended Dosing
`Regimen
`
`Apply a thin layer (approximately 1 gram) to affected area
`twice daily (morning and evening).
`
`Version date: October 12, 2018
`
`Reference ID: 4661201
`
`

`

`N Multidisciplinary Review and Evaluation: NDA 213433
`
`WINLEVI (clascoterone) cream, 1%
`
`
`Table of Contents
`
`Table of Contents.................................................................................................................i
`
`Table of Tables....................................................................................................................1
`
`Table of Figures...................................................................................................................5
`
`Reviewers of Multidisciplinary Review and Evaluation ......................................................6
`
`Glossary ..............................................................................................................................9
`
`1. Executive Summary.......................................................................................................11
`
`1.1. Product Introduction..............................................................................................11
`
`1.2. Conclusions on Substantial Evidence of Effectiveness ...........................................11
`
`1.3. Benefit-Risk Assessment ........................................................................................12
`
`1.4. Patient Experience Data .........................................................................................15
`
`2. Therapeutic Context .....................................................................................................16
`
`2.1. Analysis of Condition..............................................................................................16
`
`2.2. Analysis of Current Treatment Options..................................................................18
`
`3. Regulatory Background.................................................................................................26
`
`3.1. U.S. Regulatory Actions and Marketing History .....................................................26
`
`3.2. Summary of Presubmission/Submission Regulatory Activity.................................26
`
`4. Significant Issues From Other Review Disciplines Pertinent to Clinical
`
`Conclusions on Efficacy and Safety.............................................................................27
`
`4.1. Office of Scientific Investigations ...........................................................................27
`
`4.2. Product Quality ......................................................................................................28
`
`4.2.1. Drug Substance................................................................................................28
`
`4.2.2. Drug Product....................................................................................................28
`
`4.2.3. OPQ Recommendation ....................................................................................29
`
`5. Nonclinical Pharmacology/Toxicology ..........................................................................29
`
`5.1. Executive Summary ................................................................................................29
`
`5.2. Referenced NDAs, BLAs, DMFs...............................................................................31
`
`5.3. Pharmacology.........................................................................................................31
`
`5.3.1. Safety Pharmacology .......................................................................................32
`
`5.4. ADME/PK ................................................................................................................33
`
`5.5. Toxicology...............................................................................................................34
`
`5.5.1. General Toxicology ..........................................................................................34
`
`5.5.2. Genetic Toxicology...........................................................................................37
`
`5.5.3. Carcinogenicity ................................................................................................38
`
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`Version date: October 12, 2018
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`Reference ID: 4661201
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`

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`N Multidisciplinary Review and Evaluation: NDA 213433
`
`WINLEVI (clascoterone) cream, 1%
`
`5.5.4. Reproductive and Developmental Toxicology .................................................39
`
`5.5.5. Other Toxicology Studies .................................................................................43
`
`6. Clinical Pharmacology ...................................................................................................44
`
`6.1. Executive Summary ................................................................................................44
`
`6.1.1. Recommendations...........................................................................................45
`
`6.1.2. Postmarketing Requirements and Commitment .............................................45
`
`6.2. Summary of Clinical Pharmacology Assessment ....................................................45
`
`6.2.1. Pharmacology and Clinical Pharmacokinetics..................................................45
`
`6.2.2. General Dosing and Therapeutic Individualization ..........................................47
`
`6.2.3. Outstanding Issues...........................................................................................47
`
`6.3. Comprehensive Clinical Pharmacology Review......................................................48
`
`6.3.1. General Pharmacology and Pharmacokinetic Characteristics .........................48
`
`6.3.2. Clinical Pharmacology Questions.....................................................................49
`
`7. Sources of Clinical Data and Review Strategy...............................................................51
`
`7.1. Table of Clinical Studies..........................................................................................51
`
`7.2. Review Strategy......................................................................................................55
`
`7.2.1. Data Sources ....................................................................................................55
`
`7.2.2. Data and Analysis Quality ................................................................................55
`
`8. Statistical and Clinical Evaluation..................................................................................55
`
`8.1. Review of Relevant Individual Trials Used to Support Efficacy ..............................55
`
`8.1.1. Study Design and Endpoints ............................................................................55
`
`8.1.2. Statistical Methodologies ................................................................................56
`
`8.1.3. Subject Disposition, Demographics, and Baseline Disease
`
`Characteristics ...............................................................................................57
`
`8.1.4. Results of Coprimary Efficacy Endpoints .........................................................59
`
`8.1.5. Results of Secondary Efficacy Endpoints .........................................................62
`
`8.1.6. Efficacy Results in Subjects ≥12 Years of Age ..................................................62
`
`8.1.7. Findings in Special/Subgroup Populations.......................................................64
`
`8.2. Review of Safety.....................................................................................................74
`
`8.2.1. Safety Review Approach ..................................................................................74
`
`8.2.2. Review of Safety Database ..............................................................................75
`
`8.2.3. Adequacy of Applicant’s Clinical Safety Assessments......................................79
`
`8.2.4. Safety Results...................................................................................................81
`
`8.2.5. Analysis of Submission-Specific Safety Issues..................................................95
`
`8.2.6. Clinical Outcome Assessment Analyses Informing Safety/Tolerability..........103
`
`8.2.7. Safety Analyses by Demographic Subgroups.................................................103
`
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`Reference ID: 4661201
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`N Multidisciplinary Review and Evaluation: NDA 213433
`
`WINLEVI (clascoterone) cream, 1%
`
`8.2.8. Specific Safety Studies/Clinical Trials.............................................................103
`
`8.2.9. Additional Safety Explorations.......................................................................106
`
`8.2.10. Safety in the Postmarket Setting .................................................................109
`
`8.2.11. Integrated Assessment of Safety .................................................................109
`
`8.3. Summary and Conclusions ...................................................................................110
`
`8.3.1. Statistical Issues.............................................................................................110
`
`8.3.2. Conclusions and Recommendations..............................................................111
`
`9. Advisory Committee Meeting and Other External Consultations...............................112
`
`10. Pediatrics ..................................................................................................................112
`
`11. Labeling Recommendations......................................................................................112
`
`11.1. Prescription Drug Labeling .................................................................................112
`
`12. Risk Evaluation and Mitigation Strategies ................................................................113
`
`13. Postmarketing Requirements and Commitment ......................................................114
`
`14. Division Director (OCP) Comments ...........................................................................115
`
`15. Division Director (OB) Comments .............................................................................115
`
`16. Division Director (Clinical) Comments ......................................................................115
`
`17. Office Director (or Designated Signatory Authority) Comments ..............................116
`
`18. Appendices ...............................................................................................................117
`
`18.1. References..........................................................................................................117
`
`18.2. Clinical Assessments...........................................................................................118
`
`18.3. Clinical Pharmacology Assessments ...................................................................120
`
`18.3.1. Summary of Bioanalytical Method Validation and Performance ................120
`
`18.3.2. Clinical Pharmacology Studies .....................................................................123
`
`18.3.3. Studies Using Human Biomaterials..............................................................133
`
`18.4. Financial Disclosure ............................................................................................138
`
`18.5. Nonclinical Pharmacology/Toxicology................................................................139
`
`18.5.1. Calculations for Multiples of Exposures.......................................................139
`
`18.5.2. Nonclinical Labeling .....................................................................................140
`
`18.5.3. Review of Carcinogenicity Study Conducted With Clascoterone.................144
`
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`N Multidisciplinary Review and Evaluation: NDA 213433
`
`WINLEVI (clascoterone) cream, 1%
`
`
`Table of Tables
`
`Table 1. Classification of Clinical Forms of Acne Vulgaris .................................................18
`
`Table 2. Treatment Algorithm for Management of Acne Vulgaris....................................18
`
`Table 3. Acne Medications................................................................................................19
`
`Table 4. Summary of FDA-Approved Treatment Armamentarium Relevant to
`
`Proposed Indication Acne Vulgaris .............................................................................22
`
`Table 5. Clinical Inspection Summary ...............................................................................27
`
`Table 6. Summary of Clinical Pharmacology Review ........................................................44
`
`Table 7. Pharmacokinetics of Clascoterone in Adults and Adolescents With Acne
`
`Vulgaris .......................................................................................................................46
`
`
`Table 8. Summary of Clinical Pharmacology, Pharmacokinetics and
`
`Pharmacodynamics of Clascoterone...........................................................................48
`
`Table 9. Total Daily Amount of Clascoterone Cream 1% Evaluated in Maximal Use
`
`and Phase 3 Studies ....................................................................................................50
`
`Table 10. Clinical Trials in NDA 213433 Development Program .......................................51
`
`Table 11. Investigator Global Assessment (IGA) Scale......................................................56
`
`Table 12. Disposition of Subjects ......................................................................................58
`
`Table 13. Demographics and Baseline Disease Characteristics ........................................58
`
`Table 14. Results of the Coprimary Efficacy Endpoints at Week 12 (ITT1)........................59
`
`Table 15. Results of the Coprimary Efficacy Endpoints at Week 12 With Different
`
`Approaches for Handling Missing Data.......................................................................61
`
`Table 16. Results of the Secondary Efficacy Endpoints at Week 12 (ITT1)........................62
`
`
`Table 17. Results of the Coprimary Efficacy Endpoints at Week 12 in Subjects ≥12
`
`Years of Age (ITT1).......................................................................................................63
`
`
`Table 18. Results of the Secondary Efficacy Endpoints at Week 12 in Subjects ≥12
`
`Years of Age (ITT1).......................................................................................................63
`
`Table 19. IGA Success at Week 12 by Sex, Age, Race, and Baseline IGA Score for
`
`Study CB-03-01/25 [ITT1] ............................................................................................65
`
`Table 20. IGA Success at Week 12 by Sex, Age, Race, and Baseline IGA Score for
`
`Study CB-03-01/26 [ITT1] ............................................................................................65
`
`Table 21. Absolute Change From Baseline in Inflammatory Lesion Counts at Week 12
`
`by Sex, Age, Race, and Baseline IGA Score for Study CB-03-01/25 [ITT1] ...................66
`
`Table 22. Absolute Change From Baseline in Inflammatory Lesion Counts at Week 12
`
`by Sex, Age, Race, and Baseline IGA Score for Study CB-03-01/26 [ITT1] ...................66
`
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`Reference ID: 4661201
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`N Multidisciplinary Review and Evaluation: NDA 213433
`WINLEVI (clascoterone) cream, 1%
`Table 23. Absolute Change From Baseline in Noninflammatory Lesion Counts at
`Week 12 by Sex, Age, Race, and Baseline IGA Score for Study CB-03-01/25 [ITT1] ....67
`
`Table 24. Absolute Change From Baseline in Noninflammatory Lesion Counts at
`
`Week 12 by Sex, Age, Race, and Baseline IGA Score for Study CB-03-01/26 [ITT1] ....67
`
`Table 25. IGA Success at Week 12 by Country for Study CB-03-01/25 [ITT1]....................71
`
`Table 26. Absolute Change From Baseline in Inflammatory Lesion Counts at Week 12
`
`by Country for Study CB-03-01/25 [ITT1] ....................................................................71
`
`Table 27. Absolute Change From Baseline in Noninflammatory Lesion Counts at
`
`Week 12 by Country for Study CB-03-01/25 [ITT1] .....................................................72
`
`Table 28. IGA Success at Week 12 by Country for Study CB-03-01/26 [ITT1]....................72
`
`Table 29. Absolute Change From Baseline in Inflammatory Lesion Counts at Week 12
`
`by Country for Study CB-03-01/26 [ITT1] ....................................................................73
`
`Table 30. Absolute Change From Baseline in Noninflammatory Lesion Counts at
`
`Week 12 by Country for Study CB-03-01/26 [ITT1] .....................................................73
`
`Table 31. Safety Population, Size, and Denominators (Total Number of Subjects in
`
`Safety Population by Study)........................................................................................76
`
`Table 32. Summary of Treatment Compliance, Safety Pool A ..........................................77
`
`Table 33. Summary of Treatment Compliance in Long-Term Safety Study ......................77
`
`Table 34. Subject Disposition by Treatment in Phase 3 Pivotal Studies (Pool A)..............78
`
`Table 35. Summary of Subject Disposition, All Subjects, Long-Term Safety.....................78
`
`Table 36. Safety Assessments for Vehicle-Controlled and Open-Label Long-Term
`
`Studies in Subjects With Acne Vulgaris.......................................................................79
`
`Table 37. Overall Summary of Treatment-Emergent Adverse Events in Phase 3
`
`Pivotal Studies (Pool A, Safety Population).................................................................82
`
`Table 38. Serious Treatment-Emergent Adverse Events by System Organ Class,
`Preferred Term, and Treatment in Phase 3 Pivotal Studies (Pool A) (Safety
`Population) .................................................................................................................82
`
`Table 39. Treatment-Emergent Adverse Events Reported for ≥1% of Subjects in
`Either Treatment Group in Phase 3 Pivotal Studies (Pool A, Safety Population)........83
`
`Table 40. CB-03-01/27: Overall Summary of Subjects With Treatment-Emergent
`
`Adverse Events by Treatment Sequence From Parent Study .....................................83
`
`Table 41. Treatment-Emergent Adverse Events Leading to Discontinuation of Study
`Drug by System Organ Class, Preferred Term, and Treatment in Phase 3 Pivotal
`Studies (Pool A) (Safety Population) ...........................................................................85
`
`Table 42. Patients Discontinued Treatment Due to TEAEs ...............................................85
`
`Table 43. Treatment-Emergent Adverse Events Leading to Dose Modification by
`
`System Organ Class, Preferred Term, and Treatment in Phase 3 Pivotal Studies
`(Pool A) (Safety Population)........................................................................................86
`
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`Reference ID: 4661201
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`N Multidisciplinary Review and Evaluation: NDA 213433
`
`WINLEVI (clascoterone) cream, 1%
`
`Table 44. Summary of All Grade TEAEs by SOC and PT (More Than 1%)..........................87
`
`Table 45. Laboratory-Related Adverse Events..................................................................90
`
`Table 46. Pregnancy Outcomes and Study Treatment .....................................................91
`
`Table 47. Long-Term Safety Study CB-03-01/27 ...............................................................91
`
`Table 48. Proportion of Subjects With Clinically Important Vital Sign Values at
`Postbaseline Visits by Treatment in Study 171-7151-201, BID, Clascoterone
`Cream, 1%...................................................................................................................92
`
`Table 49. Point Estimates and 90% CIs (FDA Analysis)......................................................94
`
`Table 50. Proportion of Subjects Who Shifted to High (From Normal, Low or Not
`
`Done) ..........................................................................................................................95
`
`Table 51. Proportion of Subjects Who Shift to High (From Normal, Low or Not Done)
`
`by Age .........................................................................................................................96
`
`Table 52. Maximum Percent Change From Baseline in Potassium Level..........................96
`
`Table 53. Proportion of Subjects Who Shift to High (From Normal, Low or Not
`
`Done)* ........................................................................................................................96
`
`Table 54. Proportion of Subjects Who Shift to High (From Normal, Low or Not Done)
`
`By Age* .......................................................................................................................97
`
`Table 55. Maximum Percent Change From Baseline in Potassium Level..........................97
`
`Table 56. Investigator Rating Scales for Erythema, Edema, and Scaling/Dryness ............99
`
`Table 57. Subject Rating Scales for Stinging/Burning and Pruritus.................................100
`
`Table 58. Number (Percentage) of Subjects With Immediate and Long-Term Local
`
`Skin Reactions in Pooled Phase 3 Pivotal Studies (Safety Population) .....................101
`
`Table 59. Number (Percentage) of Subjects With Local Skin Reactions by Severity in
`
`Pooled Phase 3 Pivotal Studies (Safety Population) .................................................102
`
`Table 60. Number (Percentage) of Subjects With Treatment-Emergent (New or
`
`Worsening) Local Skin Reactions After Day 1 by Severity in Pooled Phase 3 Pivotal
`Studies (Safety Population).......................................................................................102
`
`Table 61. Overall Summary of Treatment-Emergent Adverse Events by Subgroups of
`
`Age, Gender, Race, for CB-03-01 1% Cream, BID Group in Phase 3 Pivotal Studies
`(Pool A) .....................................................................................................................103
`
`Table 62. Abnormal ACTH Stimulation Tests in Pediatric Patients .................................107
`
`Table 63. Location of Labeling Discussion for Significant High-Level Labeling Changes.113
`
`Table 64. Bioanalytical Validation Reports and Associated Clinical Studies ...................121
`
`Table 65. Bioanalytic Methods and Validation Parameters of Clascoterone and Its
`
`Metabolites in Human Plasma..................................................................................122
`
`Table 66. Validation Parameters of Cortisol in Human Serum .......................................123
`
`Table 67. Urinary Excretion of Total Clascoterone (Mean ± SD).....................................124
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`N Multidisciplinary Review and Evaluation: NDA 213433
`
`WINLEVI (clascoterone) cream, 1%
`
`Table 68. Urinary Excretion of Total Cortexolone (Mean ± SD) ......................................124
`
`Table 69. Urinary Excretion of Total Tetrahydrocortexolone (Mean ± SD).....................124
`
`Table 70. Plasma Concentrations of Clascoterone After Repeat Dosing ........................125
`
`Table 71. Urinary Excretion of Total Clascoterone (Mean ± SD).....................................125
`
`Table 72. Clascoterone Plasma Concentrations on Day 42.............................................126
`
`Table 73. Demographic Information for Study 171-7151-202........................................127
`
`Table 74. PK of Clascoterone in Adults and Adolescents Under Maximal Use
`
`Conditions.................................................................................................................128
`
`Table 75. Subjects Who Had Adrenal Suppression at Day 14/EOS .................................129
`
`Table 76. Demographic Information for Study CB-03-01/28 ..........................................130
`
`Table 77. Plasma Concentrations of Clascoterone and Cortexolone in Pediatric
`
`Subjects Who Had a Shift in Potassium From Normal to High..................................131
`
`Table 78. Pharmacokinetics of Clascoterone (Mean ± SD) in Healthy Subjects..............132
`
`Table 79. Pharmacokinetics of Cortexolone (Mean ± SD) in Healthy Subjects ...............132
`
`Table 80. Metabolism of Clascoterone in Human Plasma at 37.8°C...............................133
`
`Table 81. Structures of Clascoterone and Proposed Metabolites in Hepatocytes .........134
`
`Table 82. CYP Induction With Clascoterone in Human Hepatocytes (n=3).....................135
`
`Table 83. CYP Inhibition With Clascoterone in Pooled Human Liver Microsomes..........136
`
`Table 84. Clinical Investigators .......................................................................................138
`
`Table 85. Multiples of Exposure Based on AUC Comparisons Between MRHD and
`
`AUC Values From Nonclinical Studies Referenced in Label ......................................140
`
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`Reference ID: 4661201
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`N Multidisciplinary Review and Evaluation: NDA 213433
`WINLEVI (clascoterone) cream, 1%
`Table of Figures
`
`Figure 1. Age Distribution of Skin and Subcutaneous Disease Burden .............................16
`
`Figure 2. Pathophysiological Processes Involved in Acne Vulgaris ...................................17
`
`Figure 3. Chemical Similarity Between Clascoterone, Dihydrotestosterone, and
`
`Spironolactone............................................................................................................24
`
`Figure 4. Proposed Mechanism of Action of Clascoterone...............................................25
`
`Figure 5. Chemical Structure of Clascoterone ..................................................................28
`
`Figure 6. IGA Success at Week 12 by Center [ITT1] ...........................................................68
`
`Figure 7. Absolute Change From Baseline in Inflammatory Lesion Counts by Center
`
`[ITT1]............................................................................................................................69
`
`Figure 8. Absolute Change From Baseline in Noninflammatory Lesion Counts by
`
`Center [ITT1]................................................................................................................70
`
`Figure 9. Representative Example of Diastolic BP, Heart Rate, and Systolic Blood
`
`Pressure Over Visits in Subjects Receiving Clascoterone............................................98
`
`Figure 10. Representative Example of Diastolic BP, Heart Rate, and Systolic Blood
`
`Pressure Over Visits in Subjects Receiving Vehicle .....................................................98
`
`Figure 11. Local Tolerability Assessment by Severity, Erythema ....................................118
`
`Figure 12. Local Tolerability Assessment by Severity, Scaling/Dryness ..........................118
`
`Figure 13. Local Tolerability Assessment by Severity, Skin Atrophy ...............................119
`
`Figure 14. Local Tolerability Assessment by Severity, Pruritus.......................................119
`
`Figure 15. Trough Plasma Concentrations of Clascoterone (A) and Urinary Recovery
`
`of Total Clascoterone (B) ..........................................................................................126
`
`Figure 16. Mean Plasma Concentrations of Clascoterone in Adult and Adolescent
`
`Subjects.....................................................................................................................128
`
`Figure 17. Clascoterone Concentrations in Subjects With or Without Adrenal
`
`Suppression...............................................................................................................129
`
`Figure 18. Average Clascoterone (A) and Cortexolone (B) Trough Concentrations in
`
`Subjects With or Without Adrenal Suppression .......................................................131
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`Reference ID: 4661201
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`N Multidisciplinary Review and Evaluation: NDA 213433
`WINLEVI (clascoterone) cream, 1%
`Reviewers of Multidisciplinary Review and Evaluation
`
`Regulatory Project Manager
`Application Technical Lead
`Nonclinical Reviewer
`Nonclinical Supervisor
`Nonclinical Associate Director
`Office of Clinical Pharmacology Reviewer(s)
`Office of Clinical Pharmacology Team Leader(s)
`Clinical Reviewer
`Clinical Team Leader
`Statistical Reviewer
`Statistical Team Leader
`Cross-Disciplinary Team Leader
`Division Director or Designee
`Division Director (OCP)
`Office Director (or designated signatory authority)
`
`Dawn Williams, BSN
`Hamid Shafiei, PhD
`John P. Dougherty, PhD
`Barbara Hill, PhD
`Ron Wange, PhD
`Liping (Cindy) Pan, PhD
`Chinmay Shukla, PhD
`Natalia I. Chalmers DDS, MHSc, PhD
`David Kettl, MD
`Matthew Guerra, PhD
`Mohamed Alosh, PhD
`David Kettl, MD
`Shari L.Targum, MD, MPH, FACP, FACC
`Chandrahas G Sahajwalla, PhD
`Julie Beitz, MD
`
`Additional Reviewers of Application
`
`OPQ
`Application Technical Lead: Hamid Shafiei, Ph.D.
`Regulatory Business Process Manager: Melinda Bauelien, MS
`Drug Substance: Jeffrey Medwid, Ph.D./Donna Christner, Ph.D.
`Drug Product: Zhengfang Ge, Ph.D./Moo-Jhong Rhee, Ph.D.
`Environmental Assessment: Raanan Bloom, Ph.D./Michael Furness, Ph.D.
`Manufacturing: Amit Kokate, Ph.D./Yubing Tang, Ph.D.
`Biopharmaceutics: Swapna Pamu, Ph.D./Vidula Kolhatkar, Ph.D.
`Microbiology: Jason God, Ph.D./Denise Miller, Ph.D.
`OPQ = Office of Pharmaceutical Quality
`OPDP = Office of Prescription Drug Promotion
`OSI = Office of Scientific Investigations
`OSE = Office of Surveillance and Epidemiology
`DEPI = Division of Epidemiology
`DMEPA = Division of Medication Error Prevention and Analysis
`DRISK = Division of Risk Management
`DHOT = Division of Hematology Oncology Toxicology
`OCP = Office of Combination Products
`OB = Office of Biostatistics
`OHOP = Office of Hematology and Oncology Products
`
`Version date: October 12, 2018
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`Reference ID: 4661201
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`N Multidisciplinary Review and Evaluation: NDA 213433
`WINLEVI (clascoterone) cream, 1%
`Signatures
`
`DISCIPLINE
`
`REVIEWER
`
`OFFICE/DIVISION
`
`Hamid
`Shafiei, PhD
`
`OPA
`
`SECTIONS
`AUTHORED/
`APPROVED
`
`AUTHORED/
`APPROVED
`
`Section: 4.2
`
` X Authored
`
`Select one:
`_X_ Authored
`___ Approved
`
`Select one:
`___ Authored
`_X_ Approved
`
`Select one:
` Authored
`_X_ Approved
`
`Select one:
`_X__ Authored
`___ Approved
`
` Select one:
`___ Authored
`
`_X__ Approved
`
`Select one:
`___ Authored
`__X_ Approved
`
`OPQ ATL
`
`Nonclinical
`Reviewer
`
`Nonclinical
`Supervisor
`
`Nonclinical
`Associate
`Director
`
`Clinical
`Pharmacology
`Reviewer
`
`Clinical
`Pharmacology
`Team Leader
`
`OII/DPT-II
`
`Sections: 5, 18.5
`
`John P.
`Dougherty,
`PhD
`
`Signature:
`
`Barbara Hill,
`PhD
`
`OII/DPT-II
`
`Sections: 5, 18.5
`
`Signature:
`
`Ron Wange,
`PhD
`
`OND/IO
`
`Sections: 5, 18.5
`
`Signature:
`
`Liping
`(Cindy) Pan,
`PhD
`
`Signature:
`
`OCP/DIIP
`
`Sections: 6
`
`