Prilosec1 ® 20 mg Tablets Rx to OTC Switch Daiva Shetty, M.D. Division of Over-the-Counter Drug Products (HFD-560) Food and Drug Administration 1

Prilosec1 ® Rx to OTC Switch: Overview Regulatory History Proposed Label Target Population Actual Use Study #007 2

Differences Between the Original and Resubmission NDA Original Resubmitted Dose10 mg20 mg Target Population> 12 years> 18 years Anybody with HBHB > 2 x/week UsesRelief and prevention Prevention of frequent HB Duration10 days14 days (intermittent)(continuous) 3

Overview of the Program Actual Use Study –#007 Three Label Comprehension Studies –#02255 –#12179 –#17859 Proposed OTC Labeling Safety Update 4

Prilosec1 ® Rx to OTC Switch: Overview Regulatory History Proposed Label Target Population Actual Use Study #007 5

Proposed Label: Uses for prevention of the symptoms of frequent heartburn for 24 hours only for those who suffer heartburn two or more days a week 6

Proposed Label: Directions Adults 18 years of age or older: for prevention of frequent heartburn, swallow 1 tablet with a glass of water in the morning take every day for 14 days do not continue beyond 14 days unless directed by your doctor. If your frequent heartburn continues or returns, it could be a sign of a more serious condition. 7

Proposed Label: Warning Heartburn warning. Heartburn can be a sign of a more serious condition. Notify your doctor if you have had heartburn for 3 months or longer without talking to your doctor. 8

Prilosec1 ® Rx to OTC Switch: Overview Regulatory History Proposed Label Target Population Actual Use Study #007 9

OTC Issues for Prilosec1 ® Are consumers able to: self-select/de-select –identify risk factors self-treat –follow label directions for dosing and duration of use –follow label directions when to see their HCP 10

Actual Use Study #007: Study Design Multi-center Open-label All-comers Minimal inclusion/exclusion criteria 3-month duration 11

Primary Objective How consumers use omeprazole in naturalistic OTC conditions following proposed labeling instructions 12

13 Results: Self-Selection Participated in a self-selection interview 1,301 Answer not available 1 Self-selected product “Not appropriate” 49 Self-selected product “Appropriate” 1,251 (Self-Selection Population) Answer not available 1 Subject < 18 years of age 3 Chose not to participate 384 Chose to participate 863

14 Chose Not to Participate N=384 Study participation inconvenient115 Don’t try new medicine without MD approval104 Happy with current HB medication 32 Too expensive 19 Don’t use medication 5 Other113

15 Chose to Participate N=863 Did not meet study criteria 9 Purchased study medication 854 Did not return any diaries 92 Lost to follow-up 82 Withdrew consent 8 Adverse event 1 Investigator decision 1 Returned one or more diaries 762

16 Returned One or More Diaries N=762 Returned blank diaries 4 Returned diaries & used study drug 758 (Treated population) Not available for 3-month follow-up 109 Available for 3-month follow-up 649

Subject Disposition: Summary Excluded from Study (N=12) + 17

Demographics (Self-Selection Population N=1,251) 59% Females Years of age, mean 48 65% Caucasian 18% Black 2% Asian 1.2% American Indian 9.4% Low Literacy Group 18

Heartburn History: Duration (Self-Selection Population N=1,251) < 3 months29 (2.3%) 4-12 months99 (7.9%) 1-2 years238 (19%) 3-5 years 314 (25%) > 5 years567 (45%) 19

Heartburn History: Frequency (Self-Selection Population N=1,251) < 1 day a week169 (14%) 2-3 days a week425 (34%) 4-5 days a week 164 (13%) 6-7 days a week 489 (39%) 20

Consultation for HB with Health Care Provider (HCP): Definition Advice from a physician or supporting HCP, or Use of a prescription HB medication The contact was not confirmed Specific information was not collected (what issue was discussed and what advice was given) 21

Consultation for HB with HCP Self-Selection Population (N=1,251) 22 over 1 year (17%) within 1 year (46%) never (37%)

Correct Self-Selection: Definition HB > 2 days/week > 18 years old Not pregnant/lactating Not allergic to omeprazole No contraindicated symptoms that were not reported to HCP No contraindicated medications that were not discussed with a HCP 23

Correct Self-Selection: Results Self-Selection Population (N=1,251) Correct 76% (n=961) Incorrect 24% (n=290) HB < 1 day/week 169 Contraindicated symptoms 134 Contraindicated medications 15 Age < 18 years 3 Pregnant or nursing 1 24

Purchasing Patterns Purchase Population (N=854) 94% (799) 1 carton* 2% (20) 2 cartons 1% (8) 3 cartons 3% (27) 4 cartons * Each carton contained 14 tablets 25

Compliance with Labeled Directions Treated Population (N=758) Compliant 478 (63%) Not compliant:280 (27%) Exceeded 1 dose per day 69 (9%) Exceeded 1 tablet per dose 31 (4%) Exceeded 14 consecutive days 23 (3%) Took for less than 14 days249(33%) 26

Return of Frequent Heartburn Treated Population available for 3-month follow-up (N=649) 43% (n=276) Did not have HB 57% (n=373) Frequent HB returned: –46% (171) Antacid HB medicine –27% (99) Rx HB medicine –21% (78) OTC acid reducer –20% (75) Consulted HCP –10% (36) Changed lifestyle – 6% (22) Did not do anything 27

Study Limitations Relatively short duration (3 months) Did not address if Prilosec1 will be used intermittently (few courses over a year) Did not address the concomitant usage of other HB medications Did not assess if consumers understand that Prilosec1 is not for relief of acute HB 28

Actual Use Study: Conclusions Most of the consumers who self-selected Prilosec1 as appropriate for their use had a long history of frequent HB 29

Overall Conclusions (cont.) Even though the label stated to see HCP prior to the use of Prilosec1, 1/3 of the subjects did not do so More than half of the treated population had their HB return: –Majority switched to other HB medicine (Rx or OTC) –1/5 went to see their HCP Unclear how the interaction with HCP prior or after the use of Prilosec1 would have influenced consumer behavior 30

Overall Conclusions (cont.) Prilosec1 is likely to be used by consumers with contraindicated symptoms Prilosec1 is likely to be used by consumers with infrequent HB 31