21945Orig1s000 - Food and Drug Administration

CENTER FOR DRUG EVALUATION AND RESEARCH

APPLICATION NUMBER:

21945Orig1s000

MEDICAL REVIEW(S)

Clinical Review Barbara Wesley NDA 21-945 17-alpha hydroxyprogesterone caproate 3 February 2011

CLINICAL REVIEW

Application Type Application Number(s)

Priority or Standard Submit Date(s)

Received Date(s) PDUFA Goal Date

Division / Office

Reviewer Name(s) Review Completion Date

Established Name (Proposed) Trade Name

Therapeutic Class Applicant

Formulation(s) Dosing Regimen

Indication(s)

Intended Population(s)

NDA 21-945 Priority 12 July 2010 13 July 2010 13 April 2011 Division of Reproductive and Urologic Products Barbara Wesley, M.D., M.P.H. 3 February 2011 hydroxyprogesterone caproate Makena Progestin Hologic Inc. Injectable (Intramuscular - IM) 250 mg (1 mL) weekly from between 16 weeks, 0 days, and 20 weeks 6 days to 37 weeks of gestation or until delivery Reduction of the Risk of Preterm Birth Pregnant women with a history of at least one spontaneous singleton preterm birth

Reference ID: 2900781

Primary Medical Officer Review Barbara Wesley, M.D., M.P.H. NDA 21-945 17-alpha hydroxyprogesterone caproate Final 3 February 2011

Table of Contents

1 RECOMMENDATIONS/RISK BENEFIT ASSESSMENT.............................................. 5

1.1 Recommendation on Regulatory Action .......................................................................... 5 1.2 Risk Benefit Assessment .................................................................................................. 5

1.2.1 Efficacy ..................................................................................................................... 6 1.2.2 Safety......................................................................................................................... 7 1.2.3 Summary ................................................................................................................... 8 1.3 Recommendations for Postmarket Risk Evaluation and Mitigation Strategies................ 9 1.4 Recommendations for Postmarket Requirements and Commitments .............................. 9

2 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

2.4.1 Castor Oil ................................................................................................................ 12 2.5 Summary of Previous Regulatory Activity .................................................................... 13

2.5.1 Pre-NDA Activity.................................................................................................... 13 2.5.2 Regulatory Summary and NDA Actions................................................................. 14 2.5.3 Studies to Support NDA 21-945 (Original NDA Submission April 14, 2006)....... 18 2.5.4 Advisory Committee (August 29, 2006) ................................................................. 28 2.5.5 Literature ? Late Preterm Births.............................................................................. 30

3 ETHICS AND GOOD CLINICAL PRACTICES ............................................................ 32

3.1 Submission Quality and Integrity ................................................................................... 32 3.1.1 Institutional Review/Ethics/Consent Form: ............................................................ 32

3.2 Compliance with Good Clinical Practices...................................................................... 32 3.3 Financial Disclosures...................................................................................................... 33

4 SIGNIFICANT EFFICACY/SAFETY ISSUES RELATED TO OTHER REVIEW DISCIPLINES...................................................................................................................... 33

4.1 Chemistry Manufacturing and Controls ......................................................................... 33 4.2 Clinical Microbiology..................................................................................................... 34 4.3 Preclinical Pharmacology/Toxicology ........................................................................... 34 4.4 Clinical Pharmacology ................................................................................................... 34

5 SOURCES OF CLINICAL DATA..................................................................................... 36

6 REVIEW OF EFFICACY .................................................................................................. 36

6.1 Indication ........................................................................................................................ 36 6.1.1 Methods ................................................................................................................... 36 6.1.2 Primary Endpoint(s) ................................................................................................ 36

Reference ID: 2900781

2

Primary Medical Officer Review Barbara Wesley, M.D., M.P.H. NDA 21-945 17-alpha hydroxyprogesterone caproate Final 3 February 2011

6.1.3 Secondary Endpoints(s)........................................................................................... 37 6.1.4 Other Endpoints....................................................................................................... 38 6.1.5 Study Design ........................................................................................................... 38

7 REVIEW OF SAFETY ....................................................................................................... 47

7.7 Additional Submissions/Safety Issues............................................................................ 47 7.7.1 Data Safety Monitoring Board (DSMB) ................................................................. 47 7.7.2 Recent Safety Literature .......................................................................................... 48 7.7.3 Follow-up Study (17P-FU-004) .............................................................................. 49 7.7.4 Safety Update .......................................................................................................... 50

8 POSTMARKET EXPERIENCE........................................................................................ 51

9 APPENDICES...................................................................................................................... 52

9.1 Labeling Recommendations ........................................................................................... 52 9.2 Bibliography ................................................................................................................... 52

Reference ID: 2900781

3

Primary Medical Officer Review Barbara Wesley, M.D., M.P.H. NDA 21-945 17-alpha hydroxyprogesterone caproate Final 3 February 2011

Table of Tables

Table 1 Proportion of Subjects with Delivery at ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download