692009 5:57 PM

1
Allergan, Inc.NDA 21-701tazarotene 1.5 and 4.5
mg capsules

• Backup slides presented
• FDA Advisory Committee July 12, 2004

2
Prior and Concomitant Therapy

• Patients were not to have used
• Systemic medications (other than corticosteroids)
  known to affect bone (eg, alendronate sodium) in
  the 12 months before study entry
• Systemic retinoids (eg, isotretinoin, acitretin,
  bexarotene) or oral or injectable systemic
  corticosteroids in the 8 weeks before study entry
• PUVA, methotrexate, or cyclosporine in the 4
  weeks before study entry
• UVB treatment or topical therapies (eg, topical
  corticosteroids, topical retinoids, topical
  calcipotriene) that may have altered the course
  of psoriasis in the 2 weeks before study entry
• Daily vitamin A supplements 5,000 IU, vitamin D
  supplements 400 IU, or calcium supplements
  1,300 mg in the 7 days before study entry

C-028
3
Prior and Concomitant Therapy(cont.)

• During their participation in the study, other
  than the use of study medication, patients were
  not to use any medications that could alter the
  course of their psoriasis or could interfere with
  the evaluation of the study medication
• Therapies considered necessary for the patients
  welfare could be given at the discretion of the
  investigator
• If the decision was made to administer a
  medication that may have affected the outcome of
  the study, the medication was to be administered
  in constant doses throughout the study

C-029
4
Liver Function TestsNot Elevated Compared With
Placebo
Placebo higher than tazarotene in 12 weeks tx
study Higher than placebo and higher with long
term tx
S-035
5
Patients Treated with Oral Tazarotene Had
Greater Satisfaction with Their Study
Medication(Study 048P/049P)
Oral Tazarotene 4.5 mg 79.5were satisfied with
their study medication
Placebo 52.3were satisfied with their study
medication
Patient Satisfaction with Treatment at Week 12
Mean satisfaction scores indicate statistically
significant greater satisfaction with oral
tazarotene than with placebo (pE-134
6
Improvement in PQOL-12 is Correlated to
Improvement in OLA (048P/049P)and Greater Than
Placebo
OLA Improvement at Week 12Relative to PQOL-12
Change Scores
1 grade OLA Improvement
2 grade OLA Improvement
OLA ofmin or none
Placebo
MID1.24
-1.05, -0.62
Mean PQOL-12 Change Score
-2.08, -1.65
-2.79, -2.07
-3.42, -2.50
95 confidence interval of the mean
E-141
7
Bone Mineral Density Issue
Femoral Neck BMD Data, 95 Tolerance Region, and
/-5 Straight-Line Tolerance Region

• 94 of points in TR
• 83 in slice (vs. 81 expected)
• 11 below slice (vs. 13 exp.)
• 6 above slice (vs. 5 exp.)
• Mean shift -0.01 (0.943 vs 0.933)
• Median shift -0.003

S-212
8
Bone Fractures Reported in 9 Patients in 048P,
049P, 052P, and 050P Trials
S-086
9
No Apparent Association Between Fractures and BMD
LS lumbar spine, H total hip, FN femoral
neck
S-087
10
Patient 1115 (Apparent Loss of 50 Hip BMD Due
to Scan of Unacceptable Quality)
Unacceptable quality scan
S-183
11
Apparent Loss of 20 BMD from Baseline (Patient
3409)

• 50-year old male with obesity (151 kg), diabetes,
  and sleep apnea
• BMD assessment at limits of capability of BMD
  technology due to obesity
• Patient started with high BMD/T score
• Concomitant meds aspirin, Glucovance,
  benazepril, amfebutamone, sertraline,
  pramipexole, saw palmetto

S-206
12
Risk of Osteopenia and Osteoporosis In Patients
with 5 Loss in BMD (050P)

• Of 32 patients with 5 loss in BMD at any time
• 14 (44) had normal BMD throughout the study
• 12 (38) had osteopenia at baseline and never
  became osteoporotic
• 5 (16) developed osteopenia (from normal at
  baseline)
• None developed osteoporosis 1 (3) had
  osteoporosis at baseline and follow-up
• No greater risk of osteoporosis in patients with
  5 loss vs. patients who do not have 5 loss

S-196
13
Minimal Effects on Thyroid Function
S-188
14
Education Materials for Physicians

• What Prescribers Need to Know Brochure
• Prescriber Introduction Letter
• Prescriber certification test
• Medication Guide

R-052
15
RiskMAP Roll-out

• Broad target audience
• Registration kits for physicians and pharmacies
• Educational seminars
• Professional meetings
• Field force participation

R-055
16
Body Weight, Gender, and Age Have No Effects on
PK
Study 048P
Study 049P
PC-017
17
Logistic Regression Clinical Success Versus
Possible CovariatesStudies 048P/049P(N 689)
Clinical success None/Minimal OLA at Week 12
C-136
18
Incidence of Hyperglycemia
S-189