DRAFT SLIDES FOR NDA 21-198 ADVISORY COMMITTEE PRESENATIONS

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DRAFT SLIDES FOR NDA 21-198 ADVISORY COMMITTEE
PRESENATIONS
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Pravachol ? 10 mg Tablets Rx to OTC Switch

• Daiva Shetty, M.D.
• Division of Over-the-Counter
• Drug Products (HFD-560)
• Food and Drug Administration
• Friday, July 14, 2000

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Actual Use Studies Background

• Simulate OTC Use
• Have few exclusion criteria
• Objectives depend on the specific product and
  concerns related to that product such as
• compliance, dosing, duration of use
• off-label use
• safety and efficacy in OTC population

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Actual Use Issues for Pravachol?

• Are consumers able to
• self-diagnose
• know their own cholesterol values
• understand serum cholesterol values
• self-select
• identify risk factors for CHD

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Actual Use Issues for Pravachol?

• Are consumers able to
• self-treat hypercholesterolemia
• when to start treatment
• are they able to follow label directions for
  dosing and duration of use
• do they understand the treatment goal

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Review of Pravachol? Actual Use Trials

• PREDICT, Protocol 800-01-97
• OPTIONS, Protocol 800-03-97

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Actual Use Trials

• PREDICT
• 
  The Pravachol Experience
  
  Documented In a Consumer Trial
  
  

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Study PREDICT

• Study design
• multi-center
• randomized
• parallel
• open-label
• 6 months duration

• To test
• behavior
• efficacy
• tolerability

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Study PREDICT

• Study design (cont.)
• recruitment done via advertising (newspapers,
  radio, pharmacies)
• the call center directed interested subjects to
  the enrollment site
• the call center also served as a screening site
  for premenopausal or childbearing potential women

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Study PREDICT

• Study design (cont.)
• Inclusion criteria
• gt 18 years

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Study PREDICT

• Study design (cont.)
• Exclusion criteria
• less than 18 years old
• females of childbearing potential
• breast feeding females
• participation in a research study within the last
  30 days

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Study PREDICT

• Criteria for treatment on the label
• Total cholesterol 200-240 mg/dl
• LDL cholesterol gt 130 mg/dl

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Study PREDICT

• Primary Objective
• Proportion of OTC randomized subjects, who having
  purchased OTC Pravachol 10 mg, consult a
  physician within two months of using medication

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PREDICT Results
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PREDICT Results

• 119 subjects were ineligible to participate
• 61 (2) women of childbearing age
• Of the 11,065 who called, unknown how many were
  women of childbearing potential

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Behavior of OTC Population(n1,924)
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Treatment Guidelines
Initiate Treatment/LDL-C Goal/LDL-C
No CHD or diabetes 2 risk factors gt130 mg/dl, lt 190 mg/dl lt 130 mg/dl
No CHD or diabetes, lt1 risk factor gt160 mg/dl, lt 190 mg/dl lt 160 mg/dl
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PREDICT Results

• Lipid Profile at Baseline in Qualified and
  Treated Population
• LDL-C
• Mean 162 mg/dl 17
• Median 163 mg/dl
• TC
• Mean 245 mg/dl 21
• Median 245 mg/dl

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Behavior of OTC Treated Population

• 290 (58) withdrew from the study
• 123 were withdrawn from the study by a physician
• Discontinuation due to adverse events
• 8 OTC vs. 5 Rx
• 53 subjects were titrated to a higher dose

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PREDICT Results

• Compliance
• Assessed by pill count and self-report, and
  defined by 80-120
• 54 OTC vs. 65 Rx CI -19,-3.7
• Mean duration of treatment
• 109.4 days OTC vs. 152.5 days RX

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• Are consumers able to
• self-diagnose hypercholesterolemia?

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Knowledge about Cholesterol values Randomized
Population (n3,872)

• Healthy level TC
• lt 200 74
• Unknown 21
• Healthy level LDL-C
• lt 130 12
• Unknown 80
• Knowledge of HDL-C was not tested

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Actual Use Trials

• OPTIONS
• OTC Pravachol Trial In an Observed Naturalistic
  Setting

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Study OPTIONS

• Study design
• multi-center
• open-label
• pharmacy based
• 3 months duration

• To assess
• behavior
• compliance
• safety

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Study OPTIONS

• Study design (cont.)
• Inclusion criteria
• gt 18 years
• member of a participating HMO for at least 6
  months

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Study OPTIONS

• Study design (cont.)
• Exclusion criteria
• pregnancy or lactation
• participation in a research study within the last
  30 days
• less than 18 years old

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Study OPTIONS

• Study design (cont.)
• Recruitment was done via
• mailing the study brochure to the HMO members
• walk through traffic in the participating
  pharmacies
• radio
• newspaper

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Study OPTIONS

• Population was not representative of overall U.S.
  OTC population
• restricted to certain geographical areas
• all participants had health care insurance and
  prescription drug coverage

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Study OPTIONS

• Study design (cont.)
• Criteria for treatment on the label
• Total serum cholesterol 200-240 mg/dl
• gt 35 years for men
• gt 55 years for women

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Study OPTIONS

• Primary Objective
• To determine the proportion of subjects, who
  having purchased Pravachol 10 mg, contact their
  health care provider within 2 months of using the
  medication

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OPTIONS Results
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OPTIONS Results
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OPTIONS Results
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OPTIONS Results

• 95 (24) purchase population were not recommended
  Pravachol by their health care provider
• Median total-C level 235 mg/dl
• Median LDL-C level 151 mg/dl
• 59.8 women were lt55 years old

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Proposed Label

• Total cholesterol 200-240 mg/dl
• Bad cholesterol (LDL) gt 130 mg/dl
• Do not use
• if you are under 18 years
• if you have liver disease or drink gt3 alcoholic
  beverages daily
• if you are allergic to pravastatin

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Latest Proposed Label

• Total cholesterol 200-240 mg/dl
• Bad cholesterol (LDL) gt 130 mg/dl
• For men over 35 years of age
• For women over 45 years of age

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Overall Conclusions

• Low consumer understanding of specific serum
  cholesterol values
• Substantial number of self-selection errors
• High withdrawal rate
• Poor adherence

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Overall Conclusions

• Behavior of childbearing age women was not
  addressed in these 2 trials
• Consumer understanding was not assessed about
• the goal (to lower cholesterol)
• the length of the therapy
• titration to a higher dose
• Targeted OTC population on the current proposed
  label has not been studied