1 Omeprazole Magnesium Keith C. Triebwasser, Ph.D. Senior Director Regulatory Affairs Procter &...

1

Omeprazole Omeprazole MagnesiumMagnesium

Keith C. Triebwasser, Ph.D.Keith C. Triebwasser, Ph.D.Senior DirectorSenior Director

Regulatory AffairsRegulatory AffairsProcter & GambleProcter & Gamble

2

Rx to OTC SwitchRx to OTC Switch

OmeprazoleOmeprazolefor the Prevention offor the Prevention of

Frequent Heartburn SymptomsFrequent Heartburn Symptoms

3Target Population: People withTarget Population: People withFrequent HeartburnFrequent Heartburn

Heartburn symptoms 2 or more days Heartburn symptoms 2 or more days per week (40 million people)per week (40 million people)

Affects their daily livesAffects their daily lives

Goal: to prevent vs. treat symptomsGoal: to prevent vs. treat symptoms

4Target Population Tries to Manage Target Population Tries to Manage Frequent HeartburnFrequent Heartburn

77% use OTC medications77% use OTC medications

OTC product useOTC product use

- 80% use antacids- 80% use antacids

- 48% use OTC H- 48% use OTC H22RAsRAs

- 38% use both- 38% use both

Only 19% report satisfactionOnly 19% report satisfaction

5Current OTC Therapies Not Well-SuitedCurrent OTC Therapies Not Well-Suitedfor People with Frequent Heartburnfor People with Frequent Heartburn

Pharmacology limits effectivenessPharmacology limits effectiveness– Short duration of actionShort duration of action

– Intended for episodic heartburnIntended for episodic heartburn

Current therapies lack all day efficacyCurrent therapies lack all day efficacy

6Omeprazole Ideally Suited for Target Omeprazole Ideally Suited for Target PopulationPopulation

Pharmacology provides forPharmacology provides for– Prolonged acid suppressionProlonged acid suppression

– 24 hour prevention of symptoms24 hour prevention of symptoms

– Once daily dosingOnce daily dosing

7Omeprazole Ideally Suited for Target Omeprazole Ideally Suited for Target PopulationPopulation

Omeprazole’s excellent safety profileOmeprazole’s excellent safety profile– 15 years15 years

– 125 countries125 countries

– 450 million patient treatments450 million patient treatments

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OTC Label OTC Label

Label clearly directs consumers:Label clearly directs consumers:

How to select the productHow to select the product

How to use the productHow to use the product

What to do if symptoms continueWhat to do if symptoms continueor returnor return

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OTC Label ElementsOTC Label Elements

Target populationTarget population– Frequent heartburn sufferers (2 or more days/week)Frequent heartburn sufferers (2 or more days/week)

Indication Indication – Prevention of the symptoms of frequent heartburn Prevention of the symptoms of frequent heartburn

for 24 hoursfor 24 hours

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for 24 hoursfor 24 hours Dose Dose

– 20 mg of omeprazole as omeprazole magnesium20 mg of omeprazole as omeprazole magnesium

11





– 20 mg of omeprazole as omeprazole magnesium20 mg of omeprazole as omeprazole magnesium Directions for useDirections for use

– Take 1 tablet in the morningTake 1 tablet in the morning

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– Take 1 tablet in the morningTake 1 tablet in the morning– Take every day for 14 consecutive daysTake every day for 14 consecutive days

13






– Take 1 tablet in the morningTake 1 tablet in the morning– Take every day for 14 daysTake every day for 14 days

Instructions to see a doctorInstructions to see a doctor– If you have warning signsIf you have warning signs– If heartburn continues or returnsIf heartburn continues or returns

14

Omeprazole, properly labeled, can Omeprazole, properly labeled, can be safely and effectively used in be safely and effectively used in

an OTC settingan OTC setting

15

Presentation AgendaPresentation Agenda

OTC Omeprazole for Frequent Heartburn OTC Omeprazole for Frequent Heartburn David Peura, M.D.David Peura, M.D.

Professor of MedicineProfessor of MedicineAssociate Chief of Gastroenterology, University of VirginiaAssociate Chief of Gastroenterology, University of Virginia

Efficacy and Consumer UseEfficacy and Consumer UseDouglas Bierer, Ph.D.Douglas Bierer, Ph.D.

Director, OTC Drug Development, The Procter & Gamble Co.Director, OTC Drug Development, The Procter & Gamble Co.

Safe Use in OTC SettingSafe Use in OTC SettingNora Zorich, M.D., Ph.D.Nora Zorich, M.D., Ph.D.

Vice President, Pharmaceuticals, The Procter & Gamble Co.Vice President, Pharmaceuticals, The Procter & Gamble Co.

SummarySummaryKeith Triebwasser, Ph.D.Keith Triebwasser, Ph.D.

Senior Director, Regulatory Affairs, The Procter & Gamble Co.Senior Director, Regulatory Affairs, The Procter & Gamble Co.

SafetySafetyDouglas Levine, M.D.Douglas Levine, M.D.

Chief Medical Officer, AstraZeneca LPChief Medical Officer, AstraZeneca LP

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Proposed OmeprazoleRX to OTC Switch:

A Clinician’s Perspective

David Peura, M.D. FACP FACGProfessor of Medicine

Associate Chief of Gastroenterology and HepatologyUniversity of Virginia

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Gap in OTC Therapy for Frequent Heartburn

Heartburn frequency variesHeartburn frequency varies

Current OTC meds are inadequate Current OTC meds are inadequate therapy for frequent HBtherapy for frequent HB

Condition does not require intensive Condition does not require intensive physician involvement physician involvement

Consumers could self-manage frequent Consumers could self-manage frequent HB with effective OTC therapyHB with effective OTC therapy

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More than 50% GI patients on PPIs

Primary care physicians comfortable prescribing PPIs for frequent heartburn

Endoscopy/diagnostic tests unnecessary for uncomplicated frequent heartburn

Symptom management/prevention is current practice

Current Physician ExperienceWith PPIs and Frequent Heartburn

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OTC Omeprazole Consistent withCurrent Practice Guidelines

Therapy should be aimed at treating or preventing heartburn symptoms with

acid-reducing medications

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Frequent Heartburn Can Be Self-Managed With OTC Omeprazole

Label encourages people to see their doctor

People will continue to see doctors

Low risk/high benefit to consumer

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OTC Omeprazole Would Benefit Consumers

Symptom prevention is key

PPI best therapy to prevent frequent heartburn symptoms

Proposed dose and duration appropriate

Omeprazole safe and effective

22

Efficacy and Efficacy and Consumer UseConsumer Use

Douglas Ws. Bierer, Ph.D.Douglas Ws. Bierer, Ph.D.Director, OTC Drug DevelopmentDirector, OTC Drug Development

Procter & GambleProcter & Gamble

23Efficacy and ConsumerEfficacy and ConsumerBehavior ProgramBehavior Program

Pivotal efficacy studiesPivotal efficacy studies

Consumer understanding Consumer understanding and behavior studiesand behavior studies

– Label comprehensionLabel comprehension

– Appropriate OTC useAppropriate OTC use

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Efficacy TrialsEfficacy Trials

Two efficacy trialsTwo efficacy trials

Study populationsStudy populations– Heartburn symptoms Heartburn symptoms >> 2 days a week 2 days a week

– No physician diagnosis of GERD or erosive No physician diagnosis of GERD or erosive esophagitisesophagitis

DosingDosing– One tablet in the morning forOne tablet in the morning for

14 consecutive days14 consecutive days

EndpointEndpoint– % subjects heartburn-free% subjects heartburn-free

– % days heartburn-free% days heartburn-free

25Percent of Subjects Heartburn Free ForPercent of Subjects Heartburn Free For24 Hours: Time Course Over 14 Days 24 Hours: Time Course Over 14 Days

00

1010

2020

3030

4040

5050

6060

7070

8080

9090

11 22 33 44 55 66 77 88 99 1010 1111 1212 1313 1414

Time (days)Time (days)

% S

ub

ject

s W

ith

No

Hea

rtb

urn

% S

ub

ject

s W

ith

No

Hea

rtb

urn

Study 17120 mg OME

Study 171Placebo

Study 183 20 mg OME

Study 183Placebo

* p < .001 (day 1, day 14, across 14 days)* p < .001 (day 1, day 14, across 14 days)

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Conclusion: Efficacy StudiesConclusion: Efficacy Studies

20 mg provides prevention of heartburn 20 mg provides prevention of heartburn symptoms for 24 hourssymptoms for 24 hours

Uses:Uses:For the prevention of the symptoms ofFor the prevention of the symptoms offrequent heartburn for 24 hoursfrequent heartburn for 24 hours

Dose:Dose:20 mg20 mg

Directions:Directions:1 tablet in the morning for 14 consecutive 1 tablet in the morning for 14 consecutive daysdays

27Consumer Understanding and Consumer Understanding and Behavior ProgramBehavior Program

ObjectivesObjectives– Correct self-selectionCorrect self-selection

– Understand how to use productUnderstand how to use product

– Understand and adhere to product Understand and adhere to product warningswarnings

StudiesStudies– Label comprehension Label comprehension

– Actual use Actual use

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Label Comprehension Study DesignLabel Comprehension Study Design

Subjects recruited from 12 sites across U.S.Subjects recruited from 12 sites across U.S.

n=684n=684

Study populationStudy population

– Infrequent or no heartburnInfrequent or no heartburn

– Frequent heartburnFrequent heartburn

– Low-literacy with frequent heartburnLow-literacy with frequent heartburn

– Potential drug-drug interactionsPotential drug-drug interactions

– Pregnant/nursing Pregnant/nursing

29Label Comprehension Study ResultsLabel Comprehension Study ResultsWho Should Use the ProductWho Should Use the Product

Infrequent/Infrequent/No HeartburnNo Heartburn

22%22%

78%78%Chose CorrectlyChose Correctly

n=229n=229

30Label Comprehension Study ResultsLabel Comprehension Study ResultsWho Should Use the ProductWho Should Use the Product

FrequentFrequentHeartburnHeartburn

1%1%

99%99%Chose CorrectlyChose Correctly

n=200n=200

31Label Comprehension of Low LiterateLabel Comprehension of Low LiteratePeople with Frequent HeartburnPeople with Frequent Heartburn

Frequent heartburn situationsFrequent heartburn situations79%79%

Infrequent heartburn situationsInfrequent heartburn situations49%49%

% Correct% Correct ResponseResponse

(n=162)(n=162)

32Subjects Understood How to UseSubjects Understood How to Usethe Productthe Product

1 tablet per day1 tablet per day 95%95%

Take for 14 consecutive daysTake for 14 consecutive days 91%91%

Contact healthcare professional Contact healthcare professional before using beyond 14 daysbefore using beyond 14 days 92%92%

33Subjects Understood When Not toSubjects Understood When Not toUse/Ask a Health ProfessionalUse/Ask a Health Professional

Drug-drug interactionsDrug-drug interactions

–Generic + brand namesGeneric + brand names

82%82%–Generic names aloneGeneric names alone

50%50% Pregnant/nursingPregnant/nursing

91%91%

General warning signsGeneral warning signs 81%81%

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Actual Use Study: ObjectivesActual Use Study: Objectives

Evaluate consumer use in Evaluate consumer use in naturalistic OTC settingnaturalistic OTC setting

– Correct self-selectionCorrect self-selection

– Appropriate useAppropriate use

– Complied with label Complied with label instructionsinstructions

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Actual Use Study DesignActual Use Study Design

Design mimicked consumer Design mimicked consumer purchase decisions:purchase decisions:– Mall kiosk site – not clinical siteMall kiosk site – not clinical site

– No health care professional on siteNo health care professional on site

– No subject contact in use phaseNo subject contact in use phase

– Purchase productPurchase product

– Product repurchase allowedProduct repurchase allowed

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Follow-UpFollow-UpInterviewInterview

4 Weeks After Usage Period

Product Use/Product Use/RepurchaseRepurchase 8 Week Period

Study PhasesStudy Phases

Self Selection Self Selection DecisionDecision

At Mall Kiosk

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Disposition of SubjectsDisposition of Subjects

Population Approached at MallPopulation Approached at Malln = 5060n = 5060

Population Approached at MallPopulation Approached at Malln = 5060n = 5060

No Heartburn/No Heartburn/Not InterestedNot Interested

Not Appropriate to useNot Appropriate to usen = 3809n = 3809

No Heartburn/No Heartburn/Not InterestedNot Interested

Not Appropriate to useNot Appropriate to usen = 3809n = 3809

Said They Could Said They Could Use ProductUse Product

n = 1251n = 1251

Said They Could Said They Could Use ProductUse Product

n = 1251n = 1251

Would Not Would Not PurchasePurchasen = 385n = 385

Would Not Would Not PurchasePurchasen = 385n = 385

Agreed to Purchase ProductAgreed to Purchase Product[Self-Selection Population][Self-Selection Population]

n = 866n = 866


n = 866n = 866

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Demographics of Self-Selection PopulationDemographics of Self-Selection Population

CharacteristicCharacteristic

Gender (% female) Gender (% female) 58%58%

Race Race

% Caucasian% Caucasian 68%68%

% African American% African American 16%16%

% Hispanic% Hispanic 11%11%

Mean age/rangeMean age/range 48/18-9148/18-91

Low reading ability (REALM Test)Low reading ability (REALM Test) 8% 8%

Heartburn symptoms Heartburn symptoms 2days/wk 2days/wk 90%90%

Use OTC heartburn medicationsUse OTC heartburn medications 90%90%

Use Rx heartburn medicationsUse Rx heartburn medications 40%40%

n=866n=866

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Results of Self-Selection Results of Self-Selection

Correct self-selection ofCorrect self-selection ofall 6 selection criteriaall 6 selection criteria: : 81%81%

Heartburn Heartburn 2 days per week 2 days per week

18 years of age18 years of age

Not allergic to omeprazoleNot allergic to omeprazole

Not pregnant or nursingNot pregnant or nursing

No general warning signsNo general warning signs

No drug-drug interactionsNo drug-drug interactionsn=866n=866

40People Who Did Not CorrectlyPeople Who Did Not CorrectlySelf- SelectSelf- Select

< 18 years of age< 18 years of age 33

Pregnant/nursingPregnant/nursing 1 1

Allergic to omeprazoleAllergic to omeprazole 0 0

General warning signsGeneral warning signs 82 82

Drug-drug interactionsDrug-drug interactions 8 8

Infrequent heartburnInfrequent heartburn 86 86

NumberNumberof Subjectsof Subjects

n=866n=866

41Disposition of Subjects WhoDisposition of Subjects WhoPurchased ProductPurchased Product


n = 866n = 866


n = 866n = 866

WithdrewWithdrewConsentConsent n = 4n = 4Did Not MeetDid Not MeetStudy CriteriaStudy Criteria n = 8n = 8

WithdrewWithdrewConsentConsent n = 4n = 4Did Not MeetDid Not MeetStudy CriteriaStudy Criteria n = 8n = 8

No DiaryNo Diaryn = 96n = 96

No DiaryNo Diaryn = 96n = 96

Used Product and Used Product and Returned DiaryReturned Diary

[Use Population][Use Population]n = 758n = 758

Used Product and Used Product and Returned DiaryReturned Diary

[Use Population][Use Population]n = 758n = 758

42Subjects Are Compliant WithSubjects Are Compliant WithDosing DirectionsDosing Directions

No more than No more than 1 tablet per dose1 tablet per dose 96%96%

99% 99%

No more than No more than 1 tablet per day1 tablet per day 91%91%

98%98%

Per DosingPer Dosing Occasion OccasionPer SubjectPer Subject

43Compliance With the 14-DayCompliance With the 14-DayDosing RegimenDosing Regimen

Definition of complianceDefinition of compliance– 80-100% of the product within80-100% of the product within

14 14 ± 3 ± 3 daysdays

– Physician consultation if exceeded Physician consultation if exceeded 14 doses14 doses

(11-14 doses within 11-17 days)(11-14 doses within 11-17 days)

44Compliance With the 14-DayCompliance With the 14-DayDosing RegimenDosing Regimen

People achieved high People achieved high compliance withcompliance withdosing directionsdosing directions

79%79%AccordingAccording

to label to label directionsdirections

3% > 14 doses w/o 3% > 14 doses w/o doctor contactdoctor contact

9% 11-14 doses in > 17 days9% 11-14 doses in > 17 days

< 1% Multiple daily doses< 1% Multiple daily doses

9% < 11 doses9% < 11 doses

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Rx Therapy15%

Return of Frequent HeartburnReturn of Frequent HeartburnFour Weeks After TrialFour Weeks After Trial

No Medication8%

Antacids 22%

H2RA

9%

Antacids + H2RAs3%

No FrequentHeartburn

43%

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Actual Use Study: ConclusionsActual Use Study: Conclusions

Consumers appropriately self-selectConsumers appropriately self-select

Consumers understood the labelConsumers understood the label

Consumers used product for prevention of frequent Consumers used product for prevention of frequent heartburnheartburn

Consumers used omeprazole according to label Consumers used omeprazole according to label directionsdirections

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SummarySummary

Indication Indication – Prevention of the symptoms of frequent Prevention of the symptoms of frequent

heartburn for 24 hoursheartburn for 24 hours

Dose Dose – 20 mg of omeprazole as omeprazole 20 mg of omeprazole as omeprazole

magnesiummagnesium

Directions for useDirections for use– Take 1 tablet in the morningTake 1 tablet in the morning

– Take every day for 14 daysTake every day for 14 days

48

Our proposed label, the efficacy data Our proposed label, the efficacy data and the consumer’s abilityand the consumer’s ability

to understand and use this product to understand and use this product safely and appropriately are congruentsafely and appropriately are congruent

49

OTC OmeprazoleOTC OmeprazoleUpdate on SafetyUpdate on Safety

Doug Levine, M.D.Doug Levine, M.D.

Chief Medical OfficerChief Medical OfficerAstraZeneca LPAstraZeneca LP

50

OTC Omeprazole Product SafetyOTC Omeprazole Product Safety

Product safety is defined as adverse Product safety is defined as adverse events occurring in relation to product events occurring in relation to product use during short or long termuse during short or long term

Safety of omeprazole is established Safety of omeprazole is established based on:based on:

Clinical trials with Rx productClinical trials with Rx product Rx post-marketing surveillance Rx post-marketing surveillance OTC clinical trialsOTC clinical trials

Adverse event profile of omeprazole is Adverse event profile of omeprazole is established, and is acceptable for OTCestablished, and is acceptable for OTC

51

OTC Omeprazole Product SafetyOTC Omeprazole Product Safety

Sponsor intent = short term useSponsor intent = short term use

If unintended long-term use occurs If unintended long-term use occurs without medical supervision, product without medical supervision, product adverse event profile is acceptable adverse event profile is acceptable (based on Rx product experience)(based on Rx product experience)

52Long-term Safety Issues Not Directly Long-term Safety Issues Not Directly Related to the Product Related to the Product

Potential consequences of consumer Potential consequences of consumer behavior without medically behavior without medically supervised usesupervised use

Involves medical diseases other than Involves medical diseases other than acid reflux diseaseacid reflux disease

Involves the natural history of acid reflux Involves the natural history of acid reflux induced damage to the esophagusinduced damage to the esophagus

Not directly linked to omeprazoleNot directly linked to omeprazole

53Long-term Safety Issues Not Directly Long-term Safety Issues Not Directly Related to the ProductRelated to the Product

Not likely with alarm symptoms (labeled)Not likely with alarm symptoms (labeled)– Dysphagia (trouble swallowing food)Dysphagia (trouble swallowing food)

– Frequent chest painFrequent chest pain

– Unexplained weight lossUnexplained weight loss

– Frequent wheezing, chronic coughFrequent wheezing, chronic cough

– Chest pain with shortness of breath; sweating; Chest pain with shortness of breath; sweating; pain spreading to arm, neck or shoulders; or pain spreading to arm, neck or shoulders; or lightheadednesslightheadedness


Possible with responders who do not seek Possible with responders who do not seek medical advice (despite label instructions):medical advice (despite label instructions):

Non-neoplastic upper GI conditionNon-neoplastic upper GI condition

– Esophageal erosionsEsophageal erosions

– Gastric/duodenal ulcersGastric/duodenal ulcers

Upper GI malignanciesUpper GI malignancies

Upper GI conditions with risk of malignancyUpper GI conditions with risk of malignancy


Unlikely with upper GI malignancy Unlikely with upper GI malignancy (esophagus, stomach)(esophagus, stomach)

Different symptoms (e.g., dysphagia, Different symptoms (e.g., dysphagia, nausea, vomiting, early satiety, weight nausea, vomiting, early satiety, weight loss) do not respond to omeprazoleloss) do not respond to omeprazole

Malignancy usually present at first Malignancy usually present at first presentation for medical care, without presentation for medical care, without antecedent heartburn, other symptomsantecedent heartburn, other symptoms

Malignancy is unusual in endoscoped Malignancy is unusual in endoscoped populations with frequent heartburnpopulations with frequent heartburn


Possible with upper GI conditions with risk Possible with upper GI conditions with risk of malignancyof malignancy

Barrett’s esophagus (complication of acid reflux Barrett’s esophagus (complication of acid reflux induced esophageal damage)induced esophageal damage)

Common, but rare progression to malignancyCommon, but rare progression to malignancy

Difficult to effectively manage cancer riskDifficult to effectively manage cancer risk

Omeprazole does not increase cancer riskOmeprazole does not increase cancer risk

Omeprazole does not induce regression Omeprazole does not induce regression

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Heartburn and Esophageal CancerHeartburn and Esophageal Cancer

Increasing incidence of esophageal Increasing incidence of esophageal adenocarcinoma is not related toadenocarcinoma is not related toacid reducersacid reducers

Afflicted patients generally present without Afflicted patients generally present without heartburn or Barrett’s esophagusheartburn or Barrett’s esophagus

Presently, incidence rate approximately Presently, incidence rate approximately equals mortality rate for this cancer, equals mortality rate for this cancer, suggesting lack of clinical “signal” to draw suggesting lack of clinical “signal” to draw medical attentionmedical attention

No evidence that acid reducers mask such No evidence that acid reducers mask such “signals”“signals”

Cancer development is rareCancer development is rare Omeprazole does not increase cancer riskOmeprazole does not increase cancer risk

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ConclusionsConclusions

Product-related safety profile of Product-related safety profile of omeprazole is acceptableomeprazole is acceptable

The natural history of esophageal acid The natural history of esophageal acid reflux damage can involve rare, serious reflux damage can involve rare, serious consequencesconsequences

Omeprazole does not directly increase the Omeprazole does not directly increase the risk of esophageal adenocarcinomarisk of esophageal adenocarcinoma

Based on overall safety considerations, Based on overall safety considerations, omeprazole is acceptable for OTC useomeprazole is acceptable for OTC use

59

Benefit/Risk Assessment Benefit/Risk Assessment of Omeprazole in the of Omeprazole in the

OTC MarketOTC Market

Nora Zorich, M.D., Ph.D.Nora Zorich, M.D., Ph.D.Vice President Pharmaceuticals Vice President Pharmaceuticals

Procter & GambleProcter & Gamble

60Considerations of Chronic Use of Considerations of Chronic Use of Omeprazole Without Physician Involvement Omeprazole Without Physician Involvement

1.1. What proportion of consumers may use What proportion of consumers may use OTC omeprazole on a regular basis?OTC omeprazole on a regular basis?

2.2. Do consumers with FHB go to their Do consumers with FHB go to their physicians? Will OTC omeprazole physicians? Will OTC omeprazole change that?change that?

3.3. What benefits and risks might result What benefits and risks might result from use without physician from use without physician involvement?involvement?

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NDC Prescription Database: PPI UseNDC Prescription Database: PPI Use

1.1. What Proportion of Consumers May Use What Proportion of Consumers May Use OTC Omeprazole on a Regular Basis?OTC Omeprazole on a Regular Basis?

20.720.76+6+

4.44.455

6.26.244

9.09.033

15.415.422

44.344.311

Patients (%)Patients (%)Rx Dispensed/YearRx Dispensed/Year

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Bardhan Study DesignBardhan Study Design


Patients with frequent heartburnPatients with frequent heartburn

Controlled study to assess omeprazole Controlled study to assess omeprazole usage pattern over 1 year periodusage pattern over 1 year period

Omeprazole 20mg daily for 14 daysOmeprazole 20mg daily for 14 days

If FHB returned (in 1 year) patients selfIf FHB returned (in 1 year) patients selfmanaged additional courses of therapy managed additional courses of therapy

Bardhan et al., BMJ, 1999, 18:502-507Bardhan et al., BMJ, 1999, 18:502-507

63

Bardhan Study ResultsBardhan Study Results


72% used intermittent 14-day regimens72% used intermittent 14-day regimens

– Of these, 68% requested 3 or fewer Of these, 68% requested 3 or fewer treatment courses over the yeartreatment courses over the year

– Symptom control after 2 weeks was a Symptom control after 2 weeks was a strong predictor of outcomestrong predictor of outcome

28% required maintenance therapy at 28% required maintenance therapy at some point during the yearsome point during the year

Bardhan et al., BMJ, 1999, 18:502-507Bardhan et al., BMJ, 1999, 18:502-507

64

Actual Use Trial ResultsActual Use Trial Results

No Frequent Heartburn

43%

Antacids/H2RAs/No Medicine

42%


Rx Therapy15%


Administrative claims databaseAdministrative claims database– 21% used chronically21% used chronically

Published literaturePublished literature– 28% required maintenance therapy28% required maintenance therapy

Actual Use TrialActual Use Trial– 15% returned to prescription PPI15% returned to prescription PPI– An additional 4% took two or moreAn additional 4% took two or more

14 day regimens14 day regimensMost of the people who use Most of the people who use

omeprazole don’t use it chronicallyomeprazole don’t use it chronically

66

1.1. What proportion of consumers may use What proportion of consumers may use OTC omeprazole on a regular basis??OTC omeprazole on a regular basis??

2.2. Do consumers with FHB go to their Do consumers with FHB go to their physicians? Will OTC omeprazole physicians? Will OTC omeprazole change that?change that?

3.3. What benefits and risks might result What benefits and risks might result from use without physician from use without physician involvement?involvement?

Considerations of OTC Chronic Use of Considerations of OTC Chronic Use of Omeprazole Without Physician InvolvementOmeprazole Without Physician Involvement

67

Oliveria Study DesignOliveria Study Design

2.2. Do Consumers With FHB Go toDo Consumers With FHB Go toTheir Physicians?Their Physicians?

Survey of 2000 people with heartburnSurvey of 2000 people with heartburn

How they understand their heartburnHow they understand their heartburn

How they manage their symptomsHow they manage their symptoms

How often they have physician How often they have physician contactcontact

Oliveria et al., Arch Intern Med. 1999;159:1592-1598Oliveria et al., Arch Intern Med. 1999;159:1592-1598

68

Oliveria Study ResultsOliveria Study Results

2.2. Do Consumers With FHB Go toDo Consumers With FHB Go toTheir Physicians? Their Physicians?

Over 90% were taking therapy for Over 90% were taking therapy for symptomssymptoms

Physician contact directly correlates Physician contact directly correlates to the frequency of symptomsto the frequency of symptoms– People with frequent HB were 4 times People with frequent HB were 4 times

more likely to see their physicianmore likely to see their physician

– 78% of people with most frequent HB 78% of people with most frequent HB had physician contacthad physician contact

Oliveria et al., Arch Intern Med. 1999;159:1592-1598Oliveria et al., Arch Intern Med. 1999;159:1592-1598

69

OTC HOTC H22RA’s Effect on Physician VisitsRA’s Effect on Physician Visits

2.2. Do Consumers With FHB Go to Their Do Consumers With FHB Go to Their Physicians? Will OME Change That? Physicians? Will OME Change That?

Fallon Community Healthcare SystemFallon Community Healthcare System– 2000 patients with acid-related diseases2000 patients with acid-related diseases

Minneapolis Cross-Sectional Survey Minneapolis Cross-Sectional Survey (1993-1997)(1993-1997)– 3400 consumers3400 consumers

MEDSTAT Marketscan data base MEDSTAT Marketscan data base (1995-1998)(1995-1998)– Database of >7 million peopleDatabase of >7 million people

70

Fallon Community Healthcare SystemFallon Community Healthcare SystemPre & Post OTC HPre & Post OTC H22RARA

2.2. Do Consumers With FHB Go to Their Do Consumers With FHB Go to Their Physicians? Will OME Change That?Physicians? Will OME Change That?

0.670.670.720.72GERD-related GERD-related clinic visits/yr clinic visits/yr (mean)(mean)

7/95-7/967/95-7/967/94-7/957/94-7/95

33SE Andrade et al, Med Care; 1999; 37:424-430SE Andrade et al, Med Care; 1999; 37:424-430

71

Minneapolis Cross-Sectional Survey:Minneapolis Cross-Sectional Survey:Physician Visits in Past YearPhysician Visits in Past Year


23.523.522.022.0DyspepsiaDyspepsia

21.921.923.623.6HeartburnHeartburn

19971997(n=1238)(n=1238)

%%

19931993(n=1141)(n=1141)

%%

MJ. Shaw et al, Am J Gastroenterol 2001, 96(3):673-6MJ. Shaw et al, Am J Gastroenterol 2001, 96(3):673-6

72

MEDSTAT Marketscan Data BaseMEDSTAT Marketscan Data Base1995-19981995-1998


2.122.122.002.002.042.04

0.160.160.180.180.160.160.140.14

UGIUGIEndoscopyEndoscopy(% of pop)(% of pop)

19981998199719971996199619951995

2.092.09

Visits/UGIVisits/UGIDx Code (mean)Dx Code (mean)


Rate of physician consultation for Rate of physician consultation for heartburn doubled during the studyheartburn doubled during the study

20% contacted a doctor for the first 20% contacted a doctor for the first time about their heartburn duringtime about their heartburn duringthe study the study

53% of people taking more than53% of people taking more than14 doses, talked to their physician 14 doses, talked to their physician during or just after the studyduring or just after the study

Actual Use Trial ResultsActual Use Trial Results


The majority of people with FHB The majority of people with FHB see a doctor for their symptomssee a doctor for their symptoms

Physician visits stayed the same Physician visits stayed the same after Hafter H22RA’s were available OTCRA’s were available OTC

The Actual Use Trial suggests The Actual Use Trial suggests that physician visits will not that physician visits will not decrease and may increasedecrease and may increasewith OTC omeprazolewith OTC omeprazole

75

1.1. What proportion of consumers may use What proportion of consumers may use OTC omeprazole on a regular basis?OTC omeprazole on a regular basis?

2.2. Do consumers with FHB go to their Do consumers with FHB go to their physicians? Will OTC omeprazolephysicians? Will OTC omeprazolechange that?change that?

3.3. What benefits and risks might result from What benefits and risks might result from use without physician involvement?use without physician involvement?

Considerations of OTC Chronic Use of Considerations of OTC Chronic Use of Omeprazole Without Physician InvolvementOmeprazole Without Physician Involvement

763.3. Considerations of OTC Chronic Use of Considerations of OTC Chronic Use of Omeprazole Without Physician InvolvementOmeprazole Without Physician Involvement

The label is clear - see physician if The label is clear - see physician if FHB returnsFHB returns

OTC omeprazole a better option than OTC omeprazole a better option than current OTC therapiescurrent OTC therapies

Benefit to UserBenefit to User

77Short-term PPI Superior to Long-Term Short-term PPI Superior to Long-Term HH22RA for Healing of EsophagitisRA for Healing of Esophagitis

Chiba et al., Gastroenterology 1997, 112:1798-1810Chiba et al., Gastroenterology 1997, 112:1798-1810

783.3. Considerations of OTC Chronic Use of Considerations of OTC Chronic Use of Omeprazole Without Physician InvolvementOmeprazole Without Physician Involvement

The majority of consumers won’t The majority of consumers won’t use chronicallyuse chronically

Consumers who use chronically Consumers who use chronically will involve their physicianwill involve their physician

The risks of use without physician The risks of use without physician involvement are minimal and the involvement are minimal and the benefits are substantialbenefits are substantial

79

SummarySummary

Omeprazole will fill a critical gap in OTC Omeprazole will fill a critical gap in OTC for frequent heartburnfor frequent heartburn

The target population is those people with The target population is those people with frequent heartburnfrequent heartburn

The label is understood and it is congruent The label is understood and it is congruent with OTC omeprazole usewith OTC omeprazole use

The label should specify a 14-day regimenThe label should specify a 14-day regimen

Omeprazole is acceptable for use OTCOmeprazole is acceptable for use OTC

80

ConclusionConclusion

Omeprazole can be safely Omeprazole can be safely and effectively used OTCand effectively used OTC

1 Omeprazole Magnesium Keith C. Triebwasser, Ph.D. Senior Director Regulatory Affairs Procter &...

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Transcript of 1 Omeprazole Magnesium Keith C. Triebwasser, Ph.D. Senior Director Regulatory Affairs Procter &...