CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`022272Orig1s027
`
`MEDICAL REVIEW(S)
`
`
`
`
`
`
`
`
`

`

`CLINICAL REVIEW
`
`Application Type Supplemental NDA
`Application Number(s) 022272, Supplement 27
`Priority or Standard Priority
`Submit Date(s) December 10, 2014
`Received Date(s) December 10, 2014
`PDUFA Goal Date June 8, 2015
`Division / Office Division of Anesthesia,
`Analgesia, and Addiction
`Products/ODE II
`Reviewer Name(s) CDR Javier A. Muñiz, MD
`Review Completion Date May 15, 2015
`Established Name OxyContin
`(Proposed) Trade Name OxyContin
`Therapeutic Class Opioid analgesic
`Applicant Purdue Pharma.
`Formulation(s) Controlled-release oxycodone
`Dosing Regimen Twice daily
`Indication(s) For the management of pain
`severe enough to require daily,
`around-the-clock, long-term
`opioid treatment and for which
`alternative treatment options
`are inadequate.
`years old and older.
`
`Intended Population(s)
`
`Template Version: March 6, 2009
`
`Reference ID: 3757294
`
`(b) (4)
`
`

`

`Clinical Review
`CDR Javier A. Muñiz, MD
`NDA 022272, Supplement 27
`OxyContin (controlled-release oxycodone HCl)
`
`Table of Contents
`
`2
`
`1 RECOMMENDATIONS/RISK BENEFIT ASSESSMENT......................................... 9
`1.1 Recommendation on Regulatory Action ............................................................. 9
`1.2 Risk Benefit Assessment.................................................................................... 9
`1.3 Recommendations for Postmarket Risk Evaluation and Mitigation Strategies ... 9
`1.4 Recommendations for Postmarket Requirements and Commitments .............. 10
`INTRODUCTION AND REGULATORY BACKGROUND ...................................... 10
`2.1 Product Information .......................................................................................... 10
`2.2 Tables of Currently Available Treatments for Proposed Indications ................. 11
`2.3 Availability of Proposed Active Ingredient in the United States ........................ 12
`2.4
`Important Safety Issues With Consideration to Related Drugs......................... 12
`2.5 Summary of Presubmission Regulatory Activity Related to Submission .......... 13
`2.6 Other Relevant Background Information .......................................................... 16
`3 ETHICS AND GOOD CLINICAL PRACTICES....................................................... 17
`3.1 Submission Quality and Integrity ...................................................................... 17
`3.2 Compliance with Good Clinical Practices ......................................................... 17
`3.2.1 Site 1863A (Study OTR3001)........................................................................ 18
`3.2.2 Site 1360A (Study OTR3001)........................................................................ 19
`3.2.3 Site 0033A..................................................................................................... 20
`3.3 Financial Disclosures........................................................................................ 22
`4 SIGNIFICANT EFFICACY/SAFETY ISSUES RELATED TO OTHER REVIEW
`DISCIPLINES ......................................................................................................... 22
`4.1 Chemistry Manufacturing and Controls ............................................................ 22
`4.2 Clinical Microbiology......................................................................................... 22
`4.3 Preclinical Pharmacology/Toxicology ............................................................... 22
`4.4 Clinical Pharmacology...................................................................................... 22
`4.4.1 Mechanism of Action.................................................................................. 23
`4.4.2 Pharmacodynamics (Source: OxyContin label).......................................... 23
`4.4.3 Pharmacokinetics (Source: OxyContin label))............................................ 24
`5 SOURCES OF CLINICAL DATA............................................................................ 27
`5.1 Tables of Studies/Clinical Trials ....................................................................... 27
`5.2 Review Strategy ............................................................................................... 31
`5.3 Discussion of Individual Studies/Clinical Trials................................................. 31
`5.3.1 Study OXP3003 ............................................................................................ 31
`5.3.2 Study OTR3001 ............................................................................................ 49
`5.3.3 Study OXP1005 ............................................................................................ 74
`5.3.4 Summaries of Additional Studies .................................................................. 90
`
`Reference ID: 3757294
`
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`

`

`Clinical Review
`CDR Javier A. Muñiz, MD
`NDA 022272, Supplement 27
`OxyContin (controlled-release oxycodone HCl)
`
`6 REVIEW OF EFFICACY......................................................................................... 95
`Efficacy Summary...................................................................................................... 95
`6.1
`Indication .......................................................................................................... 96
`6.1.1 Methods ..................................................................................................... 96
`6.1.2 Demographics............................................................................................ 97
`6.1.3 Subject Disposition .................................................................................... 97
`6.1.4 Analysis of Primary Endpoint(s) ................................................................. 98
`6.1.5 Analysis of Secondary Endpoints(s)......................................................... 100
`6.1.6 Other Endpoints ....................................................................................... 100
`6.1.7 Subpopulations ........................................................................................ 100
`6.1.8 Analysis of Clinical Information Relevant to Dosing Recommendations .. 101
`6.1.9 Discussion of Persistence of Efficacy and/or Tolerance Effects............... 101
`6.1.10 Additional Efficacy Issues/Analyses......................................................... 101
`7 REVIEW OF SAFETY........................................................................................... 103
`Safety Summary ...................................................................................................... 103
`7.1 Methods.......................................................................................................... 103
`7.1.1 Studies/Clinical Trials Used to Evaluate Safety ....................................... 103
`7.1.2 Categorization of Adverse Events............................................................ 103
`7.1.3 Pooling of Data Across Studies/Clinical Trials to Estimate and Compare
`Incidence.................................................................................................. 104
`7.2 Adequacy of Safety Assessments .................................................................. 105
`7.2.1 Overall Exposure at Appropriate Doses/Durations and Demographics of
`Target Populations................................................................................... 105
`7.2.2 Explorations for Dose Response.............................................................. 105
`7.2.3 Special Animal and/or In Vitro Testing ..................................................... 105
`7.2.4 Routine Clinical Testing ........................................................................... 105
`7.2.5 Metabolic, Clearance, and Interaction Workup ........................................ 105
`7.2.6 Evaluation for Potential Adverse Events for Similar Drugs in Drug Class 105
`7.3 Major Safety Results ...................................................................................... 106
`7.3.1 Deaths...................................................................................................... 106
`7.3.2 Nonfatal Serious Adverse Events ............................................................ 109
`7.3.3 Dropouts and/or Discontinuations ............................................................ 126
`7.3.4 Significant Adverse Events ...................................................................... 131
`7.3.5 Submission Specific Primary Safety Concerns ........................................ 131
`7.4 Supportive Safety Results .............................................................................. 131
`7.4.1 Common Adverse Events ........................................................................ 132
`7.4.2
`Laboratory Findings ................................................................................. 139
`7.4.3 Vital Signs................................................................................................ 158
`7.4.4 Electrocardiograms (ECGs) ..................................................................... 174
`7.4.5 Special Safety Studies/Clinical Trials....................................................... 174
`7.4.6
`Immunogenicity........................................................................................ 174
`7.5 Other Safety Explorations............................................................................... 175
`7.5.1 Somnolence ................................................................................................ 175
`
`Reference ID: 3757294
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`

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`Clinical Review
`CDR Javier A. Muñiz, MD
`NDA 022272, Supplement 27
`OxyContin (controlled-release oxycodone HCl)
`
`7.5.1 Dose Dependency for Adverse Events .................................................... 179
`7.5.2 Time Dependency for Adverse Events..................................................... 179
`7.5.3 Drug-Demographic Interactions ............................................................... 181
`7.5.4 Drug-Disease Interactions........................................................................ 181
`7.5.5 Drug-Drug Interactions............................................................................. 181
`7.6 Additional Safety Evaluations ......................................................................... 181
`7.6.1 Human Carcinogenicity............................................................................ 181
`7.6.2 Human Reproduction and Pregnancy Data.............................................. 181
`7.6.3 Pediatrics and Assessment of Effects on Growth .................................... 181
`7.6.4 Overdose, Drug Abuse Potential, Withdrawal and Rebound.................... 181
`7.7 Additional Submissions / Safety Issues.......................................................... 181
`8 POSTMARKET EXPERIENCE............................................................................. 182
`8.1 Introduction and Background............................................................................. 182
`8.2 Results............................................................................................................... 183
`8.2.1. Adolescents (13 to 17 years of age)........................................................... 187
`8.2.2 Children (1 to 12 years of age).................................................................... 188
`8.2.3 Infants (1 month old to less than 1 year old) ............................................... 189
`8.2.4 Neonates (birth to less than 1 month old) ................................................... 190
`8.2.5 Discussion................................................................................................... 191
`9 APPENDICES ...................................................................................................... 192
`9.1
`Literature Review/References ........................................................................ 192
`9.2
`Labeling Recommendations ........................................................................... 192
`9.3 Advisory Committee Meeting.......................................................................... 193
`
`Reference ID: 3757294
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`4
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`

`

`Clinical Review
`CDR Javier A. Muñiz, MD
`NDA 022272, Supplement 27
`OxyContin (controlled-release oxycodone HCl)
`
`Table of Tables
`
`Table 1. Clinical Sites Investigated ............................................................................... 18
`Table 2. Written Request-Required Studies.................................................................. 28
`Table 3. Additional Studies in Support of the Application.............................................. 30
`Table 4. Summary of Schedule of Visits and Procedures. Study OXP3003.................. 35
`Table 5. Schedule for PK Sample Collection. Study OXP3003 ..................................... 36
`Table 6. Safety Population Demographic and Baseline Characteristics. Study OXP3003
`....................................................................................................................... 41
`Table 7. Baseline Medical Conditions Occurring in ≥ 10% of Patients. Study OXP3003
`....................................................................................................................... 42
`Table 8. Concomitant Therapies. Study OXP3003........................................................ 44
`Table 9. Patient Disposition and Reasons for Discontinuation by Age Group: Safety
`Population. Study OXP3003 .......................................................................... 46
`Table 10. Summary of Extent of Exposure Oxy Pediatric Liquid: Safety Population.
`Study OXP 3003. ........................................................................................... 47
`Table 11. Sponsor’s Summary of Efficacy Results. Study OXP3003*........................... 48
`Table 12. Summary of Schedule of Visits and Procedures. Study OTR3001................ 56
`Table 13. Multiplication Factors for Converting the Daily Dose of Prior Opioids to the
`Daily Dose of Oral OxyContin. Study OTR3001 ............................................ 59
`Table 14. Frequency of Individual Opioid Medications Utilized for Dose Conversion to
`OxyContin ...................................................................................................... 60
`Table 15. Demographic and Baseline Characteristics: Safety Population. Study
`OTR3001 ....................................................................................................... 62
`Table 16. Baseline Medical Conditions Occurring in ≥ 5% of Patients. Study OTR3001.
`....................................................................................................................... 65
`Table 17. Summary of Surgical History Prior to First Dose. Study OTR3001................ 67
`Table 18. Patient Disposition and Reasons for Discontinuation: Safety Population. Study
`OTR3001 ....................................................................................................... 70
`Table 19. Summary of Extent of Exposure to OxyContin by Age and Overall: Safety
`Population. Study OTR3001. ........................................................................ 71
`Table 20. Number and Percent of Patient with Major Protocol Deviations and Violations:
`Safety Population. Study OTR3001 ............................................................... 72
`Table 21. Schedule of Visits and Procedures Flow Chart. Study OXP1005.................. 78
`Table 22. Schedule of PK Blood Sample Collection. Study OXP1005 .......................... 80
`Table 23. Prohibited Concomitant Medications for Study OXP1005 ............................. 83
`Table 24. Safety Population Demographics and Baseline Characteristics. Study
`OXP1005 ....................................................................................................... 84
`Table 25. Baseline Medical Conditions Occurring in ≥ 10% of Patients. Study
`OXP1005. ...................................................................................................... 85
`Table 26. Extent of Exposure to Oxy Pediatric Liquid: Safety Population. Study
`OXP1005. ...................................................................................................... 86
`Table 27. Patient Disposition and Reasons for Discontinuation by Age Group: Safety
`Population. Study OXP1005. ......................................................................... 88
`
`Reference ID: 3757294
`
`5
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`

`

`Clinical Review
`CDR Javier A. Muñiz, MD
`NDA 022272, Supplement 27
`OxyContin (controlled-release oxycodone HCl)
`
`Table 28. Cumulative Extent of Exposure to Study Drug For Patients Enrolled in Study
`OTR3001 and OTR3002................................................................................ 91
`Table 29. Pooling Strategy and Number of Patients Analyzed.................................... 104
`Table 30. Listing of SAEs That Lead to Death ............................................................ 107
`Table 31. All Nonfatal Treatment-Emergent SAEs by Age Group (Group A) .............. 109
`Table 32. Summary of Reasons for Study Discontinuation. Study OXP3003............. 126
`Table 33. Summary of Reasons for Study Discontinuation. Study OTR3001.............. 127
`Table 34. Incidence of TEAEs Leading to Study Drug Discontinuation by SOC and
`Preferred Term. Study OTR3001................................................................. 128
`Table 35. Summary of Reasons for Discontinuation. Study OXP1005....................... 130
`Table 36. TEAEs* Occurring in ≥2 Patients. OXP3003 .............................................. 132
`Table 37. Incidence of TEAEs Reported in ≥5% of Patients in Any Age Group: Safety
`Population. Study OTR3001. ....................................................................... 133
`Table 38. TEAEs Occurring in ≥5% of Patients by Severity; Safety Population, Ages ≥6
`to ≤12 (N=27). Study OTR3001 ................................................................... 134
`Table 39. TEAEs Occurring in ≥5% of Patients by Severity; Safety Population, Ages ≥12
`to ≤16 (N=128). Study OTR3001 ................................................................. 135
`Table 40. Incidence of TEAEs in ≥5% of Patients in the Safety Population by Dose.
`Study OXP1005. .......................................................................................... 136
`Table 41. TEAEs Occurring in ≥5% of Patients by Severity; Safety Population, Ages
`Birth to ≤ 1month (N=12). Study OXP1005.................................................. 137
`Table 42. TEAEs Occurring in ≥2 Patients by Severity; Safety Population, Ages Birth to
`7 months to ≤4 years (N=24). Study OXP1005............................................ 138
`Table 43. Summary of Selected Laboratory Data – Mean and Mean Changes from
`Baseline. Study OXP3003. .......................................................................... 139
`Table 44. Shift Table for Hematologic Parameters From Baseline to End of Study.
`OXP3003 ..................................................................................................... 142
`Table 45. Shift Table for Blood Chemistry Parameters From Baseline to End of Study.
`OXP3003 ..................................................................................................... 143
`Table 46. Patients With Laboratory Toxicity Grades ≥ 3 After Baseline. OXP3003..... 144
`Table 47. Summary of Selected Laboratory Data – Mean and Mean Changes from
`Baseline. Study OTR3001. .......................................................................... 145
`Table 48. Shifts from Normal to Low From Baseline to End of Study for Hematologic
`Parameter Values. OTR3001....................................................................... 148
`Table 49. Shifts From Normal to High From Baseline to End of Study for Hematologic
`Parameter Values. OTR3001....................................................................... 149
`Table 50. Shift from Normal to Low From Baseline to End of Study for Blood Chemistry
`Parameter Values. OTR3001....................................................................... 150
`Table 51. Shift from Normal to High From Baseline to End of Study for Blood Chemistry
`Parameter Values. OTR3001....................................................................... 151
`Table 52. Listing of Patients With Laboratory Toxicity Grades of ≥3 After Baseline.... 152
`Table 53. Summary of Selected Laboratory Data – Mean and Mean Changes from
`Baseline. Study OXP3003. .......................................................................... 154
`
`Reference ID: 3757294
`
`6
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`

`

`Clinical Review
`CDR Javier A. Muñiz, MD
`NDA 022272, Supplement 27
`OxyContin (controlled-release oxycodone HCl)
`
`Table 54. Shift Table for Hematologic and Blood Chemistry Parameters From Normal at
`Baseline to Low/High at End of Study. OXP1005 ........................................ 156
`Table 55. Patients With Laboratory Toxicity Grades ≥ 3 After Baseline. OXP1005..... 157
`Table 56. Summary of Vital Signs Mean and Mean Changes from Baseline: Safety
`Population. Study OXP3003 ........................................................................ 158
`Table 57. Summary of Respiratory Rates. OXP3003.................................................. 160
`Table 58. Hemoglobin-Oxygen Saturation Scores ≤ 90% Postbaseline. OXP3003 .... 162
`Table 59. Mean Worst Increase and Worst Decreases in Blood Pressure and Pulse:
`Ages 6 to <12 years. OTR3001 ................................................................... 163
`Table 60. Mean Worst Increase and Worst Decreases in Blood Pressure and Pulse:
`Ages 12 to ≤ 16 years. OTR3001................................................................. 164
`Table 61. Mean Changes from Baseline to End of Study in Blood Pressure and Pulse.
`OXP1005 ..................................................................................................... 169
`Table 62. Respiratory Rates (Breaths per Minute). OXP1005..................................... 170
`Table 63. Hemoglobin-Oxygen Saturation. OXP1005................................................. 172
`Table 64. SPO2 Saturation Scores ≤ 90% Post-Baseline. OXP1005 .......................... 173
`Table 65. Summary of Average Somnolence Scores. OXP3003 ................................ 175
`Table 66. Somnolence Scores. OXP1005................................................................... 177
`Table 67. Comparison of Common TEAEs in Studies OTR3001 and OTR3002......... 180
`Table 68. Worldwide Postmarketing Cases by Seriousness and Reporter Source ..... 183
`Table 69. Worldwide Postmarketing Cases; Breakdown by Country of Incidence, Report
`Source, Age Group, and Gender ................................................................. 183
`Table 70. Summary of Pediatric AEs by Seriousness and Labeling from Marketing
`Through June 30, 2014 (per US Package Insert). ....................................... 185
`Table 71. Most Common Postmarketing AEs in Adolescents ..................................... 187
`Table 72. Most Common Postmarketing AEs in Children............................................ 188
`Table 73. Most Common Postmarketing AEs in Infants .............................................. 189
`Table 74. Most Common Postmarketing AEs in Neonates.......................................... 190
`
`Reference ID: 3757294
`
`7
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`

`

`Clinical Review
`CDR Javier A. Muñiz, MD
`NDA 022272, Supplement 27
`OxyContin (controlled-release oxycodone HCl)
`
`Table of Figures
`
`Figure 1. OXP3003 Study Schematic............................................................................ 32
`Figure 2. Summary of Patient Disposition. Study OXP3003.......................................... 45
`Figure 3. OTR3001 Study Schematic............................................................................ 50
`Figure 4. Age Distribution Breakdown, Study OTR3001 (N=155) ................................. 64
`Figure 5. Summary of Patient Disposition. Study OTR3001......................................... 69
`Figure 6. OXP1005 Study Schematic............................................................................ 75
`Figure 7. Patient Disposition and Reasons for Discontinuation by Age Group: Safety
`Population. Study OXP1005. ......................................................................... 87
`Figure 8. Pain Assessments by Dose Interval............................................................... 99
`Figure 9. Total Supplemental Opioids by Dose Interval .............................................. 100
`Figure 10. Summary of Mean Respiratory Rate Data by Dose Interval. OXP3003 ..... 161
`Figure 11. Box Plot of Respiratory Rate Over Time (Scheduled Time Points). OTR3001
`..................................................................................................................... 166
`Figure 12. Box Plot of Respiratory Rate Over Time (Post Uptitration). OTR3001 ....... 167
`Figure 13. Box Plot of SpO2 Over Time (Scheduled Time Points). OTR3001 ............. 168
`Figure 14. Box Plot of SpO2 Over Time (Post-Uptitration). OTR3001 ......................... 168
`Figure 15. Respiratory Rates by Dose Intervals. OXP1005 ........................................ 171
`Figure 16. Hemoglobin-Oxygen Saturation by Treatment Group Over Dose Intervals.
`OXP1005 ..................................................................................................... 173
`Figure 17. Somnolence Scores by Treatment Group over Dose Intervals. OXP3003. 176
`Figure 18. Somnolence scores by Dose Intervals. OXP1005...................................... 178
`
`Reference ID: 3757294
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`8
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`

`

`Clinical Review
`CDR Javier A. Muñiz, MD
`NDA 022272, Supplement 27
`OxyContin (controlled-release oxycodone HCl)
`
`1 Recommendations/Risk Benefit Assessment
`
`1.1 Recommendation on Regulatory Action
`
`Purdue Pharma L.P. (hereby known as Purdue) has submitted a supplemental NDA for
`OxyContin to apply for pediatric exclusivity and approval for updating the labeling to
`include the pediatric studies results in response to the Pediatric Written Request (PWR)
`#3, Amendment #2, issued on November 14, 2011.
`
`I recommend the approval of this supplemental NDA, with the amended labeling
`recommended by the review team. This review will not address the pediatric exclusivity
`determination although it will discuss, when appropriate, how the submitted studies
`complied with the Pediatric Written Request agreement.
`
`1.2 Risk Benefit Assessment
`
`Purdue did not request a change to the current approved indication for OxyContin
`(oxycodone hydrochloride extended-release tablets), which is for the management of
`pain severe enough to require daily, around-the-clock, long-term opioid treatment and
`for which alternative treatment options are inadequate. However, Purdue is requesting
`to extend this indication to
` Based on the
`data submitted, we recommend this indication to be approved for opioid-tolerant
`pediatric patients older than 11 years of age.
`
`At this time we do not have any approved opioid medication for the management of pain
`severe enough to require daily, around-the-clock, long-term opioid treatment
`for
`pediatric patients. These patients have immediate-release approved options that must
`be taken several times a day. The main benefit of approving this supplemental NDA is
`that it will provide these patients with a long-acting pain medication option that can be
`taken only twice a day.
`
`On one hand, opioids fall into the most potent class of analgesics that treat malignant
`and nonmalignant types of chronic pain. However, the adverse event profile includes
`life-threatening
`respiratory depression along with sedation, nausea, vomiting,
`constipation, hypotension, and pruritus. The additional risk posed by opioids is the
`abuse potential related to this class of drugs.
`
`1.3 Recommendations for Postmarket Risk Evaluation and Mitigation
`Strategies
`
`OxyContin is a member of the Extended-Release/Long-Acting (ER/LA) opioid analgesic
`Risk Evaluation and Mitigation Strategy (REMS). The central component of the ER/LA
`
`Reference ID: 3757294
`
`9
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`(b) (4)
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`

`

`Clinical Review
`CDR Javier A. Muñiz, MD
`NDA 022272, Supplement 27
`OxyContin (controlled-release oxycodone HCl)
`
`opioid analgesics REMS is an education program for prescribers (e.g., physicians,
`nurse practitioners, physician assistants). Under the REMS, sponsors of ER/LA opioid
`analgesics are making education programs available to all DEA registered prescribers,
`including prescribers of ER/LA opioid analgesics. As expected, sponsors are meeting
`this obligation by providing educational grants to accredited CE providers who are
`offering training to prescribers at no or nominal cost. These CE activities cover the
`content and messages of a blueprint developed by Food and Drug Administration for
`this purpose.
`
`No changes to the currently established Postmarket Risk Evaluation and Mitigation
`Strategies recommended.
`
`1.4 Recommendations for Postmarket Requirements and Commitments
`
`No changes to the currently established Postmarket Requirements and Commitments
`recommended.
`2 Introduction and Regulatory Background
`
`2.1 Product Information
`
`Oxycodone is semisynthetic drug with potent pain-relieving effects that is derived from
`thebaine, an alkaloid that occurs naturally in the opium poppy (Papaver somniferum).
`Oxycodone was first synthesized from in 1916 and was first used clinically the following
`year. It is an analgesic generally indicated for the relief of moderate to severe pain.
`
`In general, it is thoughts that oxycodone has a similar mechanism of action as other
`opioids: it binds to specific receptors, inhibits adenylyl-cyclase and it hyperpolarizes
`neurons, thus decreasing neuronal excitability. More specifically, oxycodone has
`different degrees of affinity and agonist activity on mu, kappa and delta opioid receptors.
`
`OxyContin is a modified-release formulation of oxycodone which was initially approved
`December 12, 1995 as 10 mg, 20 mg, and 40 mg tablets. An 80 mg tablet was
`approved in January 6, 1997, followed by a 160 mg tablet on March 15, 2000, and 15
`mg, 30 mg and 60 mg tablets on September 18, 2006. The Sponsor ceased distribution
`of the 160 mg tablet in April of 2001. Out of concerns of growing numbers of reports of
`misuse, abuse, and addiction to OxyContin, the Food and Drug Administration worked
`with Purdue to strengthen the product’s label and eventually re-formulate the product.
`The reformulation of OxyContin was intended to reduce the abuse liability of the product
`by making the modified-release characteristics more robust. In essence, the re-
`formulated tablet was designed to be more difficult to crush or dissolve, and more
`resistant to the extraction of oxycodone by chemical means. The re-formulated
`
`Reference ID: 3757294
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`

`

`Clinical Review
`
`CDR Javier A. Mufiiz, MD
`NDA 022272, Supplement 27
`OxyContin (controlled-release oxycodone HCI)
`
`OxyContin was approved in April 2010, and after a few months of overlap, the Sponsor
`ceased distribution of the non-abuse deterrent formulation of OxyContin later that year.
`
`2.2 Tables of Currently Available Treatments for Proposed Indications
`
`The table below summarizes the available US products with a chronic pain indication.
`
` Formulation
`
`Indication
`
`Fentanyl
`
`Extended-release
`fentanyl
`
`Single-entity
`hydrocodone
`
`Extended-release
`hydrocodone
`
`Management of persistent, moderate to severe chronic pain in
`opioid-tolerant patients 2 years of age and older when a
`continuous, around-the-clock opioid analgesic is required for an
`extended period of time, and the patient cannot be managed by
`other means such as non-steroidal analgesics. opioid
`combination products, or immediate-release opioids.
`
`Management of pain severe enough to require daily, around-
`the-clock, long-term opioid treatment and for which alternative
`treatment options are inadequate
`
`Combination hydrocodone- Hydrocodone-acetaminophen
`containing products
`
`Moderate to moderately severe pain
`
`Hydromorphone
`
`Methadone
`
`Immediate-release
`hydromorphone
`
`Extended-release
`hydromorphone
`
`Extended-release
`methadone
`
`Management of pain in patients where an opioid analgesic is
`appropriate
`
`Management of moderate to severe pain in opioid tolerant
`patients requiring continuous, around-the—clock opioid
`analgesia for an extended period of time
`
`Management of moderate to severe pain when a continuous,
`around-the-clock analgesic is needed for an extended period of
`time
`
`Single-entity morphine
`sulfate
`
`Immediate-release
`morphine sulfate
`
`Relief of moderate to severe acute and chronic pain where the
`use of an opioid analgesic is appropriate
`
`Extended-release morphine
`sulfate
`
`Management of moderate to severe pain when a continuous,
`around-th