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NDA/BLA Multi-Disciplinary Review and Evaluation NDA 022567/S021 Viibryd (Vilazodone Hydrochloride)

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NDA/BLA Multi-Disciplinary Review and Evaluation NDA 022567/S021 Viibryd (Vilazodone Hydrochloride) NDA/BLA Multi-disciplinary Review and Evaluation NDA 022567/s021 Viibryd (vilazodone hydrochloride) NDA/BLA Multi-Disciplinary Review and Evaluation Application Type Efficacy Supplement Application Number(s) NDA 22567/s021 Priority or Standard Priority Submit Date(s) 08/01/2019 Received Date(s) 08/01/2019 PDUFA Goal Date 02/01/2020 Division/Office Division of Psychiatry (DP)/Office of Neuroscience Review Completion Date 1/31/2020 Established/Proper Name Vilazodone hydrochloride (Proposed) Trade Name Viibryd Pharmacologic Class Selective Serotonin Reuptake Inhibitor Code name N/A Applicant Allergan Sales, LLC Dosage form 10 mg, 20 mg, and 40 mg tablets Applicant proposed Dosing 20 mg to 40 mg once daily with food Regimen Applicant Proposed Major Depressive Disorder (MDD) Indication(s)/Population(s) Applicant Proposed 370143000 SNOMED CT Indication Disease Term for each Proposed Indication Recommendation on Approval Regulatory Action Recommended Major Depressive Disorder (MDD) in adults Indication(s)/Population(s) (if applicable) Recommended SNOMED 370143000 CT Indication Disease Term for each Indication (if applicable) Recommended Dosing 20 mg to 40 mg once daily with food Regimen 1 Version date: July 7, 2019 Reference ID: 4555170 NDA/BLA Multi-disciplinary Review and Evaluation NDA 022567/s021 Viibryd (vilazodone hydrochloride) Table of Contents Table of Tables ................................................................................................................................ 4 Table of Figures ............................................................................................................................... 6 Reviewers of Multi-Disciplinary Review and Evaluation ................................................................ 7 Glossary ........................................................................................................................................... 8 1 Executive Summary ................................................................................................................. 9 Product Introduction ...................................................................................................... 9 Conclusions on the Substantial Evidence of Effectiveness ............................................ 9 Benefit-Risk Assessment .............................................................................................. 10 Patient Experience Data ............................................................................................... 11 2 Therapeutic Context .............................................................................................................. 12 Analysis of Condition .................................................................................................... 12 Analysis of Current Treatment Options ....................................................................... 12 3 Regulatory Background ......................................................................................................... 14 U.S. Regulatory Actions and Marketing History ........................................................... 14 Summary of Presubmission/Submission Regulatory Activity ...................................... 14 4 Significant Issues from Other Review Disciplines Pertinent to Clinical Conclusions on Efficacy and Safety ................................................................................................................. 16 Office of Scientific Investigations (OSI) ........................................................................ 16 Product Quality ............................................................................................................ 16 5 Nonclinical Pharmacology/Toxicology................................................................................... 17 Executive Summary ...................................................................................................... 17 Toxicology .................................................................................................................... 18 Other Toxicology Studies .................................................................................... 18 6 Clinical Pharmacology ............................................................................................................ 24 Executive Summary ...................................................................................................... 24 Summary of Clinical Pharmacology Assessment.......................................................... 24 7 Sources of Clinical Data and Review Strategy ....................................................................... 30 Table of Clinical Studies ............................................................................................... 30 Review Strategy ............................................................................................................ 31 8 Statistical and Clinical and Evaluation ................................................................................... 32 Review of Relevant Individual Trials Used to Support Efficacy .................................... 32 Study VLZ-MD-21 ................................................................................................. 32 2 Version date: July 7, 2019 Reference ID: 4555170 NDA/BLA Multi-disciplinary Review and Evaluation NDA 022567/s021 Viibryd (vilazodone hydrochloride) 8.1.1.1. Study Results ................................................................................................... 34 Study VLZ-MD-22 ................................................................................................. 38 Integrated Assessment of Effectiveness ............................................................. 45 Conclusions and Recommendations ................................................................... 46 Review of Safety ........................................................................................................... 46 Safety Review Approach ..................................................................................... 46 Review of the Safety Database ........................................................................... 47 Adequacy of Applicant’s Clinical Safety Assessments ......................................... 49 Safety Results ...................................................................................................... 50 Integrated Assessment of Safety ........................................................................ 61 Conclusions and Recommendations ............................................................................ 61 9 Pediatrics ............................................................................................................................... 62 10 Labeling Recommendations .................................................................................................. 63 Prescription Drug Labeling ........................................................................................... 63 11 Postmarketing Requirements and Commitment .................................................................. 64 12 Division Director (Clinical) Comments ................................................................................... 65 13 Appendices ............................................................................................................................ 66 Financial Disclosure ...................................................................................................... 66 Nonclinical Pharmacology/Toxicology ......................................................................... 69 3 Version date: July 7, 2019 Reference ID: 4555170 NDA/BLA Multi-disciplinary Review and Evaluation NDA 022567/s021 Viibryd (vilazodone hydrochloride) Table of Tables Table 1. Summary Table of Antidepressants Labeled for MDD in the Pediatric Population ........ 13 Table 2. Summary of Startle Response Data [Mean Overall Maximum Response Values (MAX) on PND 60 and PND 104 in Juvenile Rats] .................................................................................. 22 Table 3. Summary of Sexual Maturity Data in Juvenile Animals Treated with Vilazodone PND 21 to 90 ....................................................................................................................................... 22 Table 4. Bone Densitometry Data for the Proximal Femur in Female Rats .................................. 23 Table 5. Number of Subjects and Number of Vilazodone Observations in the PK Analysis Data Set .......................................................................................................................................... 25 Table 6. Baseline Continuous Covariate Statistics for the PK Analysis Data Set, Stratified by Study ............................................................................................................................................... 25 Table 7. Parameter Estimates of the Rich PK Model With CL and Vc on a Linear and Log-Scale . 28 Table 8. Summary Statistics for the Individual Estimates of the Secondary PK Parameters (AUCss, Cmax, Tmax, T1/2, CL/F and Vc/F) by Sampling Design and Dose Group .................................... 29 Table 9.Table of Clinical Studies for MDD in Pediatric Patients ................................................... 30 Table 10. Reason for Premature Discontinuation, n(%) ............................................................... 36 Table 11. Protocol Deviations of Randomized
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