# Presentation: 696753

## 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_
- Dose			10 mg				20 mg
- Target Population	> 12 years			> 18 years
- 				Anybody with HB		HB _>_ 2 x/week
- Uses			Relief and prevention	      	Prevention of
- 								frequent HB
- Duration		10 days			14 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**

## Results: Self-Selection

**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

## Chose Not to Participate	   N=384

**Chose **_**Not**_** to Participate****	****   N=384**

- Study participation inconvenient		115
- Don’t try new medicine without
- 	MD approval						104
- Happy with current HB medication		  32
- Too expensive						  19
- Don’t use medication				    5
- Other							113

## Chose to Participate N=863

**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

## Returned One or More Diaries  N=762

**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
- 16-91 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 months****	****29 (2.3%)**
- 			4-12 months	99 (7.9%)
- 			1-2 years		238 (19%)
- 			3-5 years 		314 (25%)
- 			> 5 years		567 (45%)

**19**

## Heartburn History: Frequency 

- 	(Self-Selection Population N=1,251)
- 			_**<**_** 1 day a week****	****	****169 (14%)**
- 			2-3 days a week		425 (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 days	249	(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**