a Bristol-Myers ,SquibbCompany 4iiiw
Worldwide Consumer Medicines
Hillsrde, New Jersey 07205 1350 Liberty Avenue 90s 551-2400
September 12,200l Dockets Management Branch (HFA-305) Food and Drug Administration Department of Health and Human Services 5630 Fishers Lane, Rm.1061 Rockville, MD 20852 Attention: Charles Ganley, MD, Director Division of OTC Drug Products (HFD-560) Food and Drug Administration Docket No. 77N-0094 / CP 15 Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Use Supplement Dear Dr. Ganley: Reference is made to the Citizen Petition (Docket No. 77N-0094 / CP 15) submitted on 7/30/01 by Bristol-Myers Squibb Company (BMS) requesting the Agency to Amend the Proposed Rule for Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Use. Due to inadvertent technical errors resulting from computer difficulties, BMS is providing correction pages to Volume 1 of the Citizen Petition. Please note that changes have been made only to the revised Figures being provided herein and that the information in the Citizen Petition, presented in the text and supporting tables, is correct. These revisions do not affect any of the summaries or conclusions. For ease of review, a listing of the changes is also provided herein. We apologize for any inconvenience this may have caused. If you have any questions or comments regarding this submission please contact me at (908) 851-6126. to Citizen Petition
Re:
Sincerely,
Director, Regulatory Affairs Worldwide Consumer Medicines Bristol-Myers Squibb Company
CC: Walt Ellenberg, Ph.D. (HFD-560)
Supplement to Citizen Petition Listing of Changes to Original Pages
Page 11
Figure A Pain Intensity Difference Tension Headache (ITT)
New Page 1 IA Revisions: Graph for Studv HPD-H203 - Deleted asterisk denoting statistical significance at 0.75 hour - Deleted asterisk denoting statistical significance at I .OO hour Graph for Study 170-02-88 - Added asterisks denoting statistical significance at 0.5, 1.00, 2.00, 3.00 & 4.00 hours
Page 12
Figure B Pain Relief Tension Headache (1-m
New Page 12A Revisions: Graph for Studv HPD-H203 - Deleted asterisk denoting statistical significance at 0.75 hour - Deleted asterisk denoting statistical significance at 1 .OO hour Graph for Pooled Studies - Repositioned asterisks to appear above APAPICAF fine at 0.50, l..OO, 1.25, 1.50, 2.00, & 3.00 hours - Added asterisk denoting statistical significance at 4.00 hours
Page 14
Figure D Pain Relief Dental Pain (ITT)
New Page 14A Revisions: Graph for Pooled Studies - Deleted asterisk denoting statistical significance at 4.0b hour
1
.
Page 38
Figure A Pain Intensity Difference Tension Headache (ITT)
New Page 38A Revisions: Graph for Studv HPD-H203 - Deleted asterisk denoting statistical significance at 0.75 hour - Deleted asterisk denoting statistical significance at 1 .OO hour
Page 39
Figure B Pain Relief Tension Headache v-f)
New Page 39A Revisions: Graph for Studv HPD-H203 - Deleted asterisk denoting statistical significance at 0.75 hour - Deleted asterisk denoting statistical significance ‘at 1 .OO hour Graph for Pooled Studies - Added asterisk dehoting statistical significance at 4.00 hours
Page 41
Figure D Pain Relief Dental Pain (ITT)
New Page 41A Revisions: Graph for Pooled Studies - Deleted asterisk denoting statistical significance at 4.01) hour
Page 59
Figure 4.1 .I Pain Intensity Difference Tension Headache (ITT)
New Page 59A Revisions: Graph for Studs HPD-H203 - Deleted asterisk denoting statistical significance at 0.75 hour - Deleted asterisk denoting statistical significance at 1.09 hour
Page 65
Figure 4.1.2 Pain Relief Tension Headache m--Q
New Page 65A Revisions: Graph for Studv HPD-H203 - Deleted asterisk denoting statistical significance at 0.75 hour - Deleted asterisk denoting statistical significance at 1 J’OO hour
, Page 72 Figure 4.2.1 Pain Intensity Difference Dental Pain (ITT) New Page 72A )I ! Revisions: Graph for Studv HPD-D105 - Added asterisk denbting statistical significance at 1.25 \ , / , New Page 78A ‘, Revisions: , Graph for Pooled Studies; - Deleted asterisk denoting statistical significance at 4.00 hour , I Page 90 Figure A Pain intensity Difference Tension Headache v-0 I ‘\
Page 78
Figure 4.2.2 Pain Relief Dental Pain (ITT)
New Page 9OA Revisions: Graph for Studv HPD-H203 - Added asterisk denoting significance at 1.25 hour Graph for Pooled Studies - Moved asterisk significance from 0.75
Page 93
Figure D Pain Relief Dental Pain (ITT)
New Page 93A Revisions: i Graph for Pooled Studies I Deleted asterisk denoting statistical significance at 4.00 hour \
I I
1 .
Figure A Pain intensity Difference Tension Headache (ITT)
Study HPD-H203
2.0 1.8 1.6 k 1.4 1.2 1.0
0.8 0.6
0.4 0.2 0.0 0.25 0.50 0.75 1.00 1.25 1.50 2.00 HOW 3.00 4.00
2.0 1.8
Study 170-01-88 * I
Study 170-02-88
Pooled Studies
0.0 4
025
0.50
075
I.03
1.25
1.50
*.w HOW
3.00
4w
-+-APAP
IOOOmg / CAF 130mg
w
- APAP 1 OOOmg
-
PLACEBO
* APAP 1000 mg/CAF 130 mg significantly greater than APAP 1000 mg
BRISTOL-MYERS SQUIBB Hillside, New Jersey 07205
IIA
Figure 6 Pain Relief Tension Headache (ITT)
Study HPD-HZ03
4.00 3.50 3.00 2.50 2 2.00 1.50 1.00 0.50 0.00 0.25 0.50 0.75 1.00 1.25 1.50 2.00 Hour 3.00 4.00
T
Study 170-01-88
Hour
Hour
Pooled Studies
Hour -APAP IOOOmg / CAF 130mg --I -APAP IOOOmca PLACEBO
* APAP 1000 mg/CAF 130 mg significantly greater than APAP 1000 mg
BRISTOL-MYERS SQUIBB Hillside, New Jersey 07205
12A
14
Figure D Pain Relief Dental Pain (ITT)
Study HPD-DIOB Study HPD-D104 2.50 I
Studv 171-01-88
Pooled Studies
-APAP -APAP
1OOOmg ! CAF 130mg IOOOmdCAF 65mp
--JI
-APAP
1000mg
-PLACEBO
* APAP 1000 mg/CAF significantly greater than APAP 1000 mg
BRISTOL-MYERS SQUIBB Hillside, New Jersey 07205
14A
P
*
12
Figure A Pain Intensity Difference Tension Headache (ITT)
Study HPD-H2b3
2.0 1.8 1.6 1.4
0.8 0.6 0.4 0.2 0.0 0.25 0.50 0.75 1.00 1.25 1.50 2.00 3.00 4.00
study
1704waa
Study 170-02-88
Pooled Studies
4 025 0.50 0.75 1.M 1.25 l.zx *.w SW 4.03
Hour APAP 1 OOOmg I CAF 130mg --I - APAP IOOOmg -PLACEBO
* APAP 1000 mg/CAF 130 mg significantly
greater than APAP 1000 mg
BRISTOL-MYERS SQUIBB Hillside, New Jersey 07205
38A
13
Figure B Pain Relief Tension Headache (ITT)
Study HPD-HZ03
3.50
2.50 2.00 1.50 1.00 0.50 0.00 0.25 0.50 0.75 1.00 1.25 1.50 2.00 HOW
Study 170-01-88
Study 170-02-88
Pooled Studies
00-J 025 053 0.75 1.w 115 150 200 HO”R 3.m 400
J
-APAP
IOOOmg ! CAF 130mg
-
-APAP
1000mg
-
PLACEBO
* APAP 1000 mg/CAF 130 mg significantly
greater than APAP 1000 mg
BRISTOL-MYERS SQUIBB Hillside, New Jersey 07205
39A
Figure D Pain Relief Dental Pain (ITT)
Study HPD-D104 Study HP’D-DIOB
Study 171-01-88
Pooled Studies
2.5
i
*
2.0
1.5
---
-i,
l --I
i
0.25
0.50
0.75
1.00
1.25
1.50
2.00 “our
3.00
4.00
-APAP ---APAP
IOOOmg / CAF 130mg IOOOmglCAF 65mg
M
-APAP
IOOOmg
-PLACEBO
* APAP 1000 mg/CAF significantly greater than APAP 1000 mg
BRISTOL-MYERS SQUIBB Hillside, New Jersey 07205
41A
33
Figure 4.1.1 Pain Intensity Difference Tension Headache (ITT)
Study HPD-HZ03
2.0 1.0 1.6 1.4 1.2 g 1.0 0.8 0.6 0.4 0.2 0.0 0.25 0.50 0.75 1.00 1.25 1.50 2.00 Hour 3.00 4.00
Study 170-01-88
2.0 ,
Study 170-02-88
Pooled Studies
025
0.50
0.75
100
125
1.50
2w
3.w
4.c.z
-+-
APAP 1OOOmg I CAF 130mg
Hour -m - APAP IOOOmg
-PLACEBO
*APAP 1000 mg/CAF 130 mg significantly greater than APAP 1000 mg
BRISTOL-MYERS SQUIBB Hillside, New Jersey 07205
59A
Figure 4.1.2 Pain Relief Tension Headache
Study HPD-I4203
(ITT)
3.50 3.00 2.50
0.25 0.60 0.75 1.00 1.25 1.50 2.00 3.00 4.00
~ i
Study 170-01-88
*1 4.0,
Study 170-02-88
Pooled Studies
-APAP
1 OOOmg / CAF 130mg
-
-APAP
1 OOOmg
-
PLACEBO
*APAP 1000 mg/CAF 130 mg significantly
greater than APAP 1000 mg
BRISTOL-MYERS SQUIBB Hillside, New Jersey 07205
65A
46
Figure 4.2.1 Pain Intensity Difference Dental Pain (ITT)
Study HPD-D104 1.5, Study HPD-D105
0.9
P
0.6
0.3
0.0
-0.3
HOW ,,5 , Study 171-01-88
Pooled Studies
HOW -APAP IOOOmg / CAF 130mg - APAP IOOOmg e PLACEBO
l
APAP 1000 mg/CAF significantly
greater than APAP 1000 mg
BRISTOL-MYERS SQUIBB Hillside, New Jersey 07205
72A
52
Figure 4.2.2 Pain Relief Dental Pain (ITT)
Studv HPD-DIOS
Study HPD-D104
Study 171-01-88
2.w
Hour
-A
-APAP ---APAP
1 OOOmg I CAF 130mg lOOOm~/CAF 65mg
*
-APAP
1 OOOmg
-PLACEBO
* APAP 1000 mg/CAF significantly greater than APAP 1000 mg
BRISTOL-MYERS SQUIBB Hillside, New Jersey 07205
78A
64
Figure A Pain Intensity Difference Tension Headache (ITT)
Study HPD-HZ03
2.0 1.8 1.6 1.4
_a 1.2 Q 1.0
0.6 0.6 0.4 0.2 0.0 0.25 0.50 0.75 1.00 1.25 1.50 2.00 HOW 3.00 4.00
-+
APAP
I ooomg
I
CAF 130mg
Hour -w - APAP IOOOmg
+
PLACEBO
* APAP 1000 mg/CAF 130 mg significantly greater than APAP 1000 mg
BRISTOL-MYERS SQUIBB Hillside, New Jersey 07205
90A
Figure D Pain Relief Dental Pain (ITT)
Study HPD-D104 * Study HPD-DIOB *
0.5
Study 171X11-88
2w
3.M)
4.w
Hour Pooled Studies
2.5
-APAP -APAP
IOOOmg / CAF 130mg 1000mq / CAF 65ma
-
-APAP
IOOOmg
-PLACEBO
+ APAP 1000 mg/CAF significantly greater than APAP 1000 mg
BRISTOL-MYERS SQUIBB Hillside, New Jersey 07205
93A