`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`210361Orig1s000
`
`MULTI-DISCIPLINE REVIEW
`Summary Review
`Office Director
`Cross Discipline Team Leader Review
`Clinical Review
`Non-Clinical Review
`Statistical Review
`Clinical Pharmacology Review
`
`

`

`NDA Multi-disciplinary Review and Evaluation – NDA 210361
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`
`
`NDA Multi-disciplinary Review and Evaluation
`Application Type NDA – 505(b)(2)
`Application Number(s) 210361
`Priority or Standard Standard
`Submit Date(s) August 31, 2017
`Received Date(s) August 31, 2017
`PDUFA Goal Date
`June 30, 2018
`Division/Office DDDP/ODE III
`Review Completion Date See DARRTS electronic signature page
`Established Name Glycopyrronium
`(Proposed) Trade Name QBREXZA
`Pharmacologic Class Anticholinergic agent
`Code name DRM04
`Applicant Dermira, Inc.
`Formulation Cloth
`Dosing Regimen For topical use only. Apply Qbrexza once daily to both axillae
`using a single cloth
`For the topical treatment of primary axillary hyperhidrosis in
`adults and children 9 years of age and older
`Approval
`
`Applicant Proposed
`Indication(s)/Population(s)
`Recommendation on
`Regulatory Action
`Recommended
`Indication(s)/Population(s)
`
`Qbrexza is an anticholinergic indicated for topical treatment of
`primary axillary hyperhidrosis in adults and pediatric patients 9
`years of age and older.
`
`1
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`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4284160
`
`

`

`NDA Multi-disciplinary Review and Evaluation – NDA 210361
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`
`
`Table of Contents
`
`Reviewers of Multi-Disciplinary Review and Evaluation ................................................................ 8
`
`Additional Reviewers of Application ............................................................................................. 11
`
`Glossary ........................................................................................................................................ 12
`
`1 Executive Summary............................................................................................................... 14
`1.1. Product Introduction ....................................................................................................... 14
`1.2. Conclusions on the Substantial Evidence of Effectiveness........................................... 15
`1.3. Benefit-Risk Assessment ............................................................................................... 16
`1.4. Patient Experience Data ................................................................................................ 20
`
`2
`
`Therapeutic Context .............................................................................................................. 21
`2.1. Analysis of Condition...................................................................................................... 21
`2.2. Analysis of Current Treatment Options.......................................................................... 21
`
`3 Regulatory Background......................................................................................................... 23
`3.1. U.S. Regulatory Actions and Marketing History ............................................................ 23
`3.2. Summary of Presubmission/Submission Regulatory Activity........................................ 23
`
`4 Significant Issues from Other Review Disciplines Pertinent to Clinical Conclusions on
`Efficacy and Safety................................................................................................................ 25
`4.1. Office of Scientific Investigations (OSI) ......................................................................... 25
`4.2. Product Quality ............................................................................................................... 29
`4.3. Clinical Microbiology....................................................................................................... 34
`4.4. Devices and Companion Diagnostic Issues .................................................................. 34
`
`5 Nonclinical Pharmacology/Toxicology .................................................................................. 35
`5.1. Executive Summary ....................................................................................................... 35
`5.2. Referenced NDAs, BLAs, DMFs.................................................................................... 36
`5.3. Pharmacology................................................................................................................. 36
`5.3.1. Glycopyrronium Muscarinic M3 Receptor Binding, study No. SSCG10933 .......... 36
`5.4. ADME/PK........................................................................................................................ 37
`5.5. Toxicology ...................................................................................................................... 39
`5.5.1. General Toxicology ................................................................................................. 39
`5.5.2. Genetic Toxicology ................................................................................................. 40
`5.5.3. Carcinogenicity........................................................................................................ 41
`5.5.4. Reproductive and Developmental Toxicology........................................................ 42
`5.5.5. Other Toxicology Studies........................................................................................ 42
`
`2
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`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
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`Reference ID: 4284160
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`

`

`NDA Multi-disciplinary Review and Evaluation – NDA 210361
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`
`6 Clinical Pharmacology ........................................................................................................... 43
`6.1. Executive Summary ....................................................................................................... 43
`6.1.1. Recommendations .................................................................................................. 44
`6.1.2. Post-Marketing Requirements and Commitment(s) ............................................... 44
`6.2. Summary of Clinical Pharmacology Assessment .......................................................... 44
`6.2.1. Pharmacology and Clinical Pharmacokinetics ....................................................... 44
`6.2.2. General Dosing and Therapeutic Individualization................................................. 46
`6.3. Comprehensive Clinical Pharmacology Review ............................................................ 46
`6.3.1. General Pharmacology and Pharmacokinetic Characteristics............................... 46
`6.3.2. Clinical Pharmacology Questions........................................................................... 55
`
`7 Statistical and Clinical Evaluation ......................................................................................... 57
`7.1. Sources of Clinical Data and Review Strategy .............................................................. 57
`7.1.1. Table of Clinical Studies ......................................................................................... 57
`7.1.2. Review Strategy ...................................................................................................... 60
`7.2. Review of Relevant Individual Trials Used to Support Efficacy..................................... 60
`7.2.1. Study Design and Endpoints .................................................................................. 60
`7.2.2. Statistical Methodologies ........................................................................................ 63
`7.2.3. Patient Disposition, Demographic and Baseline Characteristics ........................... 66
`7.2.4. Gravimetrically-Measured Sweat Production Co-Primary Endpoint Results......... 68
`7.2.5. Axillary Sweating Daily Diary Item #2 Co-Primary Endpoint Results .................... 77
`7.2.6. Comparison of Gravimetrically-Measured Sweat and ASDD Item #2 ................... 82
`7.2.7. Results for the Secondary Endpoints ..................................................................... 83
`7.2.8. Findings in Special/Subgroup Populations............................................................. 84
`7.2.8.1. Sex, Race, Age, and Geographic Region ....................................................... 84
`7.2.8.2. Other Special/Subgroup Populations .............................................................. 87
`7.3. Review of Safety ............................................................................................................ 90
`7.3.1. Safety Review Approach ........................................................................................ 90
`7.3.2. Review of the Safety Database .............................................................................. 91
`7.3.3. Adequacy of Applicant’s Clinical Safety Assessments .......................................... 94
`7.3.4. Safety Results ......................................................................................................... 95
`7.3.5. Analysis of Submission-Specific Safety Issues.................................................... 106
`7.3.5.1. Adverse Events of Special Interest ............................................................... 106
`7.3.5.2.
`Local Skin Reactions ..................................................................................... 108
`7.3.6. Safety Analyses by Demographic Subgroups...................................................... 109
`7.3.7. Specific Safety Studies/Clinical Trials .................................................................. 110
`7.3.8. Additional Safety Explorations .............................................................................. 113
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`3
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`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
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`Reference ID: 4284160
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`

`

`NDA Multi-disciplinary Review and Evaluation – NDA 210361
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`
`7.3.9. Safety in the Postmarket Setting .......................................................................... 115
`7.3.10.
`Integrated Assessment of Safety .................................................................. 115
`7.4. SUMMARY AND CONCLUSIONS............................................................................... 117
`7.4.1. Statistical Issues ................................................................................................... 117
`7.4.2. Conclusions and Recommendations .................................................................... 118
`
`8 Advisory Committee Meeting and Other External Consultations ....................................... 119
`
`9 Pediatrics ............................................................................................................................. 119
`
`10 Labeling Recommendations................................................................................................ 119
`10.1.
`Prescribing Information............................................................................................. 119
`10.2.
`Patient Labeling ........................................................................................................ 119
`
`11 Risk Evaluation and Mitigation Strategies (REMS)............................................................. 119
`
`12 Postmarketing Requirements and Commitments ............................................................... 119
`
`13 Appendices .......................................................................................................................... 120
`13.1.
`References ............................................................................................................... 120
`13.2.
`Financial Disclosure ................................................................................................. 120
`13.3.
`Nonclinical Pharmacology/Toxicology ..................................................................... 122
`13.3.1.
`Nonclinical Labeling....................................................................................... 124
`13.4. OCP Appendices (Technical documents supporting OCP recommendations)....... 129
`13.4.1.
`Summary of Bioanalytical Method Validation and Performance .................. 129
`13.4.2.
`Individual Study Reports ............................................................................... 129
`13.4.2.1. Study DRM04-HH07 ..................................................................................... 129
`13.4.2.2. Study DRM04-HH02 ..................................................................................... 139
`13.4.2.3. Study DRM04-HH01 ..................................................................................... 143
`13.4.2.4. Study W0266-01 (Proof of Concept Study) .................................................. 146
`13.4.2.5.
`In vitro Drug-Drug Interaction Studies .......................................................... 147
`13.5.
`Clinical/Biostatistics .................................................................................................. 151
`
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`4
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`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
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`Reference ID: 4284160
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`

`

`NDA Multi-disciplinary Review and Evaluation – NDA 210361
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`
`
`Table of Tables
`
`
`Table 1: Summary of Clinical Pharmacology Review .................................................................... 43
`Table 2: Summary of Pharmacokinetics of DRM04 ...................................................................... 45
`Table 3: Clinical Pharmacology Studies and Investigational Drug Formulations Used................. 47
`Table 4: Summary of Subjects Demographics .............................................................................. 48
`Table 5: Summary of PK Parameters (Excluding and Including Outlier Data) of DRM04-HH07 ... 49
`Table 6: Comparison of Relative Exposure: DRM04 on Day 5 vs Cuvposa on Day 15 .................. 50
`Table 7: Comparison of Relative Exposure: DRM04 Pediatrics Day 5 vs DRM04 Adults Day 5 .... 51
`Table 8: Identified Exceptionally High Concentrations in Pediatric Subjects ............................... 52
`Table 9: DRM04-HH02 Summary of Glycopyrronium Pharmacokinetic Parameters ................... 53
`Table 10: Method Validation Parameters for the Assays for Measurement of Glycopyrronium in
`Human Plasma .............................................................................................................................. 54
`Table 11: Key Clinical Trials Relevant to NDA 210361 – Glycopyrronium cloth, 2.4% for Primary
`Axillary Hyperhidrosis ................................................................................................................... 58
`Table 12: Hyperhidrosis Disease Severity Scale (HDSS) ................................................................ 61
`Table 13: Disposition of Subjects .................................................................................................. 66
`Table 14: Subject Demographics................................................................................................... 67
`Table 15: Baseline Disease Characteristics ................................................................................... 68
`Table 16: Missing Gravimetrically-Measured Sweat Production Data by Visit ............................ 68
`Table 17: Gravimetrically-Measured Sweat Production Results .................................................. 70
`Table 18: Change in Gravimetrically-Measured Sweat Production from Baseline to Week 4 -
`Sensitivity Analyses ....................................................................................................................... 75
`Table 19: Sensitivity Analysis Evaluating the Impact of Site 502 in Trial HH05 ............................ 77
`Table 20: Missing Weekly Mean ASDD Item #2 Data by Visit....................................................... 78
`Table 21: Axillary Sweating Daily Diary (ASDD) Item #2 Results................................................... 78
`Table 22: ASDD Item #2 Sensitivity Analyses ................................................................................ 80
`Table 23: Results for the Secondary Endpoints at Week 4 ........................................................... 84
`Table 24: ASDD Item #2 Success at Week 4 by Gender, Age, Race, and Geographic Region ...... 85
`Table 25: Efficacy Results by Site – Trial HH04 ............................................................................. 88
`Table 26: Efficacy Results by Site – Trial HH05 ............................................................................. 89
`Table 27: Safety Database for Glycopyrronium: Safety Population, Size and Denominators ...... 91
`Table 28: Summary of Extent of Exposure (DRM04-HH01, DRM04-HH02, DRM04-HH04, DRM04-
`HH05, DRM04-HH06, DRM04-HH07, DRM04-HH08, and W0266-01 Pooled).............................. 92
`Table 29: Summary of Subject Demographic Characteristics (DRM04-HH04 and DRM04-HH05
`Pooled; Safety Population) ........................................................................................................... 93
`Table 30: Summary of Subjects Who Had a Serious Adverse Event ............................................. 96
`Table 31: Overview of Treatment-Emergent Adverse Events (DRM04- HH04 and DRM04-HH05
`Pooled; Safety Population) ........................................................................................................... 99
`Table 32: Overview of Treatment-Emergent Adverse Events (DRM04-HH06; Safety Population)
`..................................................................................................................................................... 100
`Table (cid:1007)(cid:1007)(cid:855) (cid:94)(cid:437)(cid:373)(cid:373)(cid:258)(cid:396)(cid:455) (cid:381)(cid:296) (cid:100)(cid:28)(cid:4)(cid:28)(cid:400) (cid:90)(cid:286)(cid:393)(cid:381)(cid:396)(cid:410)(cid:286)(cid:282) (cid:296)(cid:381)(cid:396) (cid:1096) (cid:1005)(cid:1081) (cid:381)(cid:296) (cid:94)(cid:437)(cid:271)(cid:361)(cid:286)(cid:272)(cid:410)(cid:400) (cid:381)(cid:374) (cid:94)(cid:410)(cid:437)(cid:282)(cid:455) (cid:24)(cid:396)(cid:437)(cid:336) (cid:894)(cid:87)(cid:381)(cid:381)(cid:367)(cid:286)(cid:282) (cid:87)(cid:346)(cid:258)(cid:400)(cid:286) (cid:1007)
`studies, DRM04-HH04 and DRM04-HH05, Safety Population)1 ................................................. 100
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`5
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`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
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`Reference ID: 4284160
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`

`

`NDA Multi-disciplinary Review and Evaluation – NDA 210361
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`
`Table 34: Summary of TEAEs Reported ...................................................................................... 102
`(cid:100)(cid:258)(cid:271)(cid:367)(cid:286) (cid:1007)(cid:1009)(cid:855) (cid:4)(cid:282)(cid:448)(cid:286)(cid:396)(cid:400)(cid:286) (cid:90)(cid:286)(cid:258)(cid:272)(cid:410)(cid:349)(cid:381)(cid:374)(cid:400) (cid:75)(cid:272)(cid:272)(cid:437)(cid:396)(cid:396)(cid:349)(cid:374)(cid:336) (cid:349)(cid:374) (cid:1096)(cid:1006)(cid:1081) (cid:381)(cid:296) (cid:94)(cid:437)(cid:271)(cid:361)(cid:286)(cid:272)(cid:410)(cid:400) ........................................................ 103
`Table 36: Summary of TEAEs Reported for > 2% of Subjects (DRM04-HH06; Safety Population)
`..................................................................................................................................................... 104
`Table 37: Summary of TEAEs Reported for > 2% of Subjects Overall, by Age Group (DRM04-
`HH06; Safety Population)............................................................................................................ 109
`Table 38: Summary of assays used for quantification of glycopyrronium levels in the clinical
`development program ................................................................................................................ 129
`Table 39: Concentration-time profile of the individuals with outlier concentrations on Day 1 and
`Day 5 ........................................................................................................................................... 131
`Table 40: Summary of Pharmacokinetic Parameters (Including All data) .................................. 134
`Table 41: Summary of Pharmacokinetic Parameters (Excluding Outliers) ................................. 135
`Table 42: Comparison of Relative Exposure (Including All data) ................................................ 136
`Table 43: Comparison of Relative Exposure (Excluding Outliers) ............................................... 137
`Table 44: Summary of Subject Demographics and Baseline Characteristics .............................. 140
`Table 45: DRM04-HH02 Summary of Glycopyrronium Pharmacokinetic Parameters ............... 142
`Table 46: Summary of Plasma Concentrations of Glycopyrronium (Subgroup of DRM04-HH01)
`..................................................................................................................................................... 145
`Table 47: DRM04-HH01 Summary of PK parameters on Day 1 .................................................. 145
`Table 48: Randomization of Study Subjects in 6 Groups ............................................................ 147
`Table 49: Summary (Mean % Remaining Activity) of Glycopyrrolate Effects on CYP Activity ... 149
`Table 50: Axillary Sweating Daily Diary (ASDD) Questions ......................................................... 151
`Table 51: Change from Baseline in Gravimetrically-Measured Sweat at Week 4 by Gender, Race,
`Age, and Geographic Region ....................................................................................................... 152
`
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`6
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`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
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`Reference ID: 4284160
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`

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`NDA Multi-disciplinary Review and Evaluation – NDA 210361
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`
`
`Table of Figures
`
`
`Figure 1: Axillary Sweating Daily Diary (ASDD) Item #2 ................................................................ 61
`Figure 2: Axillary Sweating Daily Diary Children (ASDD-C) ........................................................... 62
`Figure 3: Change from Baseline in Sweat Production by Visit and Sweat Production by Visit for
`Subjects in Trial HH04 (Observed Data) ........................................................................................ 70
`Figure 4: Sweat Production by Visit for Extreme Outlier Subjects in Trial HH04 ......................... 71
`Figure 5: Effect of 4 Outliers on Multiple Imputation - Subject DRM04-HH04-407-0605............ 72
`Figure 6: Effect of 4 Outliers on Multiple Imputation - Subject DRM04-HH04-402-0104............ 72
`Figure 7: Effect of 4 Outliers on Multiple Imputation - Subject DRM04-HH04-405-0428............ 73
`Figure 8: Effect of 4 Outliers on Multiple Imputation - Subject DRM04-HH04-455-2503............ 73
`Figure 9: Median Change in Gravimetrically-Measured Sweat Production by Study Visit .......... 76
`Figure 10: Changes in Weekly Mean ASDD Item #2 from Baseline to Week 4 Distribution ........ 79
`Figure 11: Weekly Mean ASDD Item #2 at Week 4 Distribution .................................................. 79
`Figure 12: Proportion of Subjects with ASDD Item #2 Success by Visit........................................ 81
`Figure 13: ASDD Item #2 Daily Results for 9 Vehicle Subjects in Trial HH05 (Observed) ............. 82
`Figure 14: Change from Baseline in Gravimetrically-Measured Sweat Production Versus Change
`in Weekly Mean ASDD Item #2 Score at Week 4.......................................................................... 83
`Figure 15: Change from Baseline in Gravimetrically-Measured Sweat Production at Week 4 by
`Sex, Race, Ethnicity, and Age Group ............................................................................................. 86
`Figure 16: Change from Baseline in Gravimetrically-Measured Sweat Production at Week 4 by
`Region – Trial HH04....................................................................................................................... 87
`Figure 17: Individual Plasma Concentration-Time Profile Including All Data ............................. 138
`Figure 18: Individual Plasma Concentration-Time Profile .......................................................... 141
`Figure 19: Change from Baseline in Gravimetrically-Measured Sweat at Week 4 by Site ......... 153
`
`7
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`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4284160
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`

`

`NDA Multi-disciplinary Review and Evaluation - NDA 210361
`
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`Reviewers of Multi-Disciplinary Review and Evaluation
`
`OFFICE/DNISION
`
`SECTIONS
`
`AUTHORED/
`
`ACKNOWLEDGED/
`APPROVED
`
`Product Quality
`Team Lead
`
`Yichun Sun, PhD
`
`Branch V/
`Division of New
`Drug Products ||
`
`Sections: 1.1, 4.2
`
`Dig'tally signed byYichun Sun -5
`Signature: Yic h u n S u n —S fléé‘ifigipmfltfl?
`032342.]92003m.100_1.l=13m393310
`Date: 2018.06.18 12:05:28 -04'00'
`
`AUTHOREDI
`
`ACKNOWLEDGEDI
`APPROVED
`
`Select one:
`
`_J Authored
`J Acknowled ed
`—
`g
`1 ! Approved
`
`Select one:
`i Authored
`
` 8
`
`Nonclinical
`
`Reviewer
`
`Nonclinical
`
`Supervisor
`
`Norman See, PhD ODE |||/ DDDP
`
`Sections: 5, 13.3
`
`Acknowledged
`
`Digitally signed by Norman A. See-S
`SignatureNorman A. See -S wamwmwmmwwm
`Date: 2018.06.18 12:27:07 —04'00'
`
`Approved
`
`Barbara A. Hill,
`PhD
`
`ODE Ill/DDDP
`
`Sections: 5, 13.3
`
`Select one:
`
`Authored
`
`_ Acknowledged
`
`J Approved
`
`.
`_
`Signature. Ba rba ra A. I
`
`C
`Digitally signed by Barbara A. Hill -5
`DN: c=US, o=U.S. Government, ou=l-IHS, ou=FDA, ou=People,
`I I I I 'S 092342.19200300.100.1.1=1300098991,cn=Barbara A. Hill —5
`Date: 2018.06.18 13:27:12 ~04'00'
`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4284160
`
`

`

`NDA Multi-disciplinary Review and Evaluation - NDA 210361
`
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`OFFICE/DWISION
`
`SECTIONS
`
`AUTHORED/
`
`ACKNOWLEDGED/
`APPROVED
`
`AUTHORED/
`
`ACKNOWLEDGED/
`APPROVED
`
`.Iihye Ahn,
`PharmD
`
`OCP—DCP |||
`
`Sections: 6, 13.4
`
`Acknowledged
`
`Approved
`
`Signature: Jihye Ahn -5 (Affiliate)
`
`Digltally signed by thye Ahn -5 (Affiliate)
`DN: c=US. o=U.S. Government, ou=HHS. ou=FDA. ou=People,
`0.9234119200300J (X11 .l=2001814798, cn=thye Ahn -S (Amllate)
`Date: 2018.06.18 14:56:07 —04'00'
`
`i Approved
`
`Clinical
`
`Pharmacology
`Reviewer
`
`Clinical
`
`Pharmacology
`Team Leader
`
`.
`.
`.
`Blostatlstlcs
`
`Reviewer
`
`Biostatistics
`
`Team Leader
`
`ChinmayShukla,
`PhD
`
`OCP-DCP lll
`
`Sections: 6, 13.4
`
`wwwmmflnws
`Mcfloflmwiwm
`09131119200111qu.1 =moo3mu
`Signature: Chinmay Shukla -5 wmwmms
`Data 1mm“ ISflHJZW
`
`Rebecca Hager,
`PhD
`
`OTS/OB/DBIII
`
`5 ct'
`
`1: 5'°"s
`
`:7.1,7.2, 7.4,
`
`Select one:
`
`Authored
`
`Acknowledged
`
`J Approved
`
`Select one:
`
`J Authored
`
`Acknowledged
`
`Approved
`
`WNWWMmiHflH-S
`Signature: Rebecca S. Hager -S wmmemm
`M 20mm; IHEIQW
`
`Mohamed Alosh,
`PhD
`
`OTS/OB/DBIII
`
`Sections: 7.1, 7.2, 7.4,
`13.5
`
`Select one:
`
`Authored
`
`Acknowledged
`
`Signature: Mohamed A.
`Alosh -S
`
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`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`9
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`Reference ID: 4284160
`
`

`

`NDA Multi-disciplinary Review and Evaluation - NDA 210361
`
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`OFFICE/DWISION
`
`SECTIONS
`AUTHORED/
`ACKNOWLEDGED/
`
`APPROVED
`
`Laura Lee
`Johnson, PhD
`
`OTS/OB/DBIH
`
`Sections: 7.1, 7.2, 7.4,
`13.5
`
`_
`_
`_
`OB DIVISIon
`DIrector (DBIII)
`
`AUTHOREDI
`ACKgggglngD/
`
`Select one:
`
`Authored
`
`Acknowledged
`
`J Approved
`
`Dlgltally signed by Laura L Johnson —5
`Signature: Laura L. Johnson -S Mamwamanwm
`Date: 2018.06.18 17:14:10 —04'00'
`
`Select one:
`
`Carol Langley,
`MD
`
`ODE ||| DDDP
`I
`
`,
`_
`Cllnlcal
`_
`ReVIewer
`
`Sections: 1.1, 1.2, 1.3, i Authored
`2, 3, 4.1, 7.1, 7.3, 7.4,
`8, 9, 10, 11, 12, 13.1,
`13.2
`
`—
`
`Acknowledged
`
`Approved
`
`
`
`-
`
`_
`
`5'8"ature. ca r0 I L. La n g I ey “S 0.9.2342.192003(X).100.1.1=2002148838,cn=CarolLLangley—5
`
`Digitally signed by Carol L Langley -S
`DN: c=US, o=U.S. Government. ou=HHS, ou=FDA, ou=People,
`
`Date: 2018.06.19 13:52:17 —04'00'
`
`.
`.
`CIInIcaI
`Team Leader
`
`D 'dK ttI,MD
`a‘"
`e
`
`ODE ||| DDDP
`/
`
`Select one:
`
`Sections: 1.1, 1.2, 1.3, J Authored
`2 3 4.1 7.1 7.3 7.4
`'
`'
`’
`’
`’
`’
`8,9,10,11,12,13.1, _ Acknowledged
`13.2
`
`V, Approved
`
`_
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`
`°
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`
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`
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`
`Digltally slgned by Davld L Kettl —S
`DN:c=US,o=U.S.Govemment, ou=HHS,ou=FDA, ou=People,
`cn=Davld L Kettl —s, 0.9.2342.19200300.100.1.l=1300383857
`Date: 2018.06.19 14:04:46 -04'00'
`
`Select one:
`
`KendallA.
`Marcus, MD
`
`ODE Ill/DDDP
`
`.
`.
`Sectlons. 1
`
`Director - DDDP
`
`Authored
`
`Acknowledged
`
`Approved
`
`Signature: see DARRTS electronic signature page
`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`10
`
`Reference ID: 4284160
`
`

`

`NDA Multi-disciplinary Review and Evaluation – NDA 210361
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`
`Additional Reviewers of Application
`
`Deputy Director
`Deputy Director for Safety
`Associate Director for Labeling
`Associate Director for Regulatory
`Affairs, ODE III
`OPQ-Drug Substance
`OPQ-Drug Product
`OPQ-Microbiology
`OPQ-Facility
`OPQ-Process
`OPQ-RBPM
`Statistician - DB VI
`OPDP
`DMPP
`
`Jill A. Lindstrom, MD, FAAD
`Tatiana Oussova, MD, MPH
`Nancy Xu, MD
`Wes Ishihara, MEM
`
`Friedrich Burnett, PhD
`Caroling Strasinger, PhD
`Xia Xu, PhD
`Carl Lee
`Mesfin Abdi, PhD
`Bamidele (Florence) Aisida
`Malick Mbodj, PhD
`Laurie Buonaccorsi, /Matthew Falter
`Shawna Hutchins, MPH, BSN, RN/LaShawn Griffiths,
`MSHS-PH, BSN, RN
`Bei Yu, PhD/Janice Pohlman, MD, MPH
`Madhuri Patel. PharmD/Sarah Vee, PharmD
`Tri Bui-Nguyen, PhD
`
`OSI
`OSE/DMEPA
`OSE-SRPM
`DB=Division of Biometrics
`DCP=Division of Clinical Pharmacology
`DDDP=Division of Dermatology and Dental Products
`DEPI=Division of Epidemiology
`DMEPA=Division of Medication Error Prevention and Analysis
`DMPP=Division of Medical Policy Programs
`OB=Office of Biostatistics
`OCP=Office of Clinical Pharmacology
`ODE=Office of Drug Evaluation
`OPQ=Office of Pharmaceutical Quality
`OPDP=Office of Prescription Drug Promotion
`OSI=Office of Scientific Investigations
`OSE=Office of Surveillance and Epidemiology
`OTS=Office of Translational Sciences
`RBPM=Regulatory Business Project Manager
`SRPM=Safety Regulatory Project Manager
`
`
`
`11
`
`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4284160
`
`

`

`NDA Multi-disciplinary Review and Evaluation – NDA 210361
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`
`Glossary
`
`
`AC
`ADME
`AE
`
`ANCOVA
`ASDD
`ASDD-C
`BLA
`
`BPCA
`
`BRF
`
`CBER
`
`CDER
`
`CDRH
`
`CDTL
`
`CFR
`
`CMC
`
`CMH
`
`COA
`
`COSTART
`CRF
`
`CRO
`
`CRT
`
`CSR
`
`CSS
`
`DMC
`
`ECG
`
`eCTD
`
`EOP2
`
`ETASU
`FDA
`
`FDAAA
`FDASIA
`GCP
`
`GRMP
`HDSS
`
`ICH
`
`IND
`
`IQR
`
`ISE
`
`ISS
`
`ITT
`
`
`advisory committee
`absorption, distribution, metabolism, excretion
`adverse event
`analysis of covariance
`Axillary Sweating Daily Diary
`Axillary Sweating Daily Diary Children
`biologics license application
`Best Pharmaceuticals for Children Act
`Benefit Risk Framework
`Center for Biologics Evaluation and Research
`Center for Drug Evaluation and Research
`Center for Devices and Radiological Health
`Cross-Discipline Team Leader
`Code of Federal Regulations
`chemistry, manufacturing, and controls
`Cochran-Mantel-Haenszel
`Clinical Outcome Assessment
`Coding Symbols for Thesaurus of Adverse Reaction Terms
`case report form
`contract research organization
`clinical review template
`clinical study report
`Controlled Substance Staff
`data monitoring committee
`electrocardiogram
`electronic common technical document
`End-of-Phase 2
`elements to assure safe use
`Food and Drug Administration
`Food and Drug Administration Amendments Act of 2007
`Food and Drug Administration Safety and Innovation Act
`good clinical practice
`good review management practice
`Hyperhidrosis Disease Severity Scale
`International Conference on Harmonization
`Investigational New Drug
`interquartile range
`integrated summary of effectiveness
`integrated summary of safety
`intent to treat
`
`12
`
`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4284160
`
`

`

`NDA Multi-disciplinary Review and Evaluation – NDA 210361
`QBREXZA (glycopyrronium) cloth, 2.4%
`
`
`IWRS
`interactive web-based randomizat