1. Orlistat OTC, 60 mg capsules GlaxoSmithKline (GSK) Consumer Healthcare New Drug Application 21-887 Actual Use Study NM17285 Joint Meeting of the Nonprescription Drugs Advisory Committee and Endocrinologic and Metabolic Advisory Committee Bethesda, Maryland January 23, 2006 Karen B. Feibus, M.D. Medical Officer Division of Nonprescription Clinical Evaluation Joint Meeting of the Nonprescription Drugs Advisory Committee and Endocrinologic and Metabolic Advisory Committee Bethesda, Maryland January 23, 2006 Karen B. Feibus, M.D. Medical Officer Division of Nonprescription Clinical Evaluation Center for Drug Evaluation and Research

2. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 2 Important elements of an actual use study (AUS)  Attempts to simulate OTC use of the product  Few exclusion criteria  Self selection: –Do people correctly choose to use or not use the product based on the label (ideally tested previously in LC studies)?  Compliance: –Do people dose and use the product based on the label directions?  Efficacy information often limited by open-label, uncontrolled design.  Objectives are product dependent  Attempts to simulate OTC use of the product  Few exclusion criteria  Self selection: –Do people correctly choose to use or not use the product based on the label (ideally tested previously in LC studies)?  Compliance: –Do people dose and use the product based on the label directions?  Efficacy information often limited by open-label, uncontrolled design.  Objectives are product dependent

3. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 3 Actual Use Issues and Objectives for Orlistat OTC  Who will use orlistat OTC?  Do subjects correctly choose to use or not use orlistat OTC based on label warnings and indications?  Do subjects dose orlistat correctly?  Do subjects lose weight?  Are there safety concerns? –Do subjects take a multivitamin correctly while using orlistat? –Do non overweight subjects choose to use orlistat? –Are there unexpected adverse events with orlistat use in the OTC environment?  Who will use orlistat OTC?  Do subjects correctly choose to use or not use orlistat OTC based on label warnings and indications?  Do subjects dose orlistat correctly?  Do subjects lose weight?  Are there safety concerns? –Do subjects take a multivitamin correctly while using orlistat? –Do non overweight subjects choose to use orlistat? –Are there unexpected adverse events with orlistat use in the OTC environment?

4. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 4 Study Design  90 days  18 U.S. pharmacies, six geographical areas  Certified weight scale in each pharmacy  Recruitment: in-store advertising; newspaper ads where recruitment slow.  Advertising notified consumers of compensation  Enrolled individuals ages 18 years and older  Subjects able and available to complete telephone interviews  Subjects with a “Do Not Use” condition could participate in self-selection but could not purchase orlistat.  90 days  18 U.S. pharmacies, six geographical areas  Certified weight scale in each pharmacy  Recruitment: in-store advertising; newspaper ads where recruitment slow.  Advertising notified consumers of compensation  Enrolled individuals ages 18 years and older  Subjects able and available to complete telephone interviews  Subjects with a “Do Not Use” condition could participate in self-selection but could not purchase orlistat.

5. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 5 Self-selection process  Consumer presented with orlistat package and told: Imagine you are in a store and this is a new over- the-counter medicine. You can take as much time as you need to look at the packaging. Let me know when you are finished.  Self-selection question asked when consumer finished examining the package: Do you think this medication is appropriate for you to use?  Consumer presented with orlistat package and told: Imagine you are in a store and this is a new over- the-counter medicine. You can take as much time as you need to look at the packaging. Let me know when you are finished.  Self-selection question asked when consumer finished examining the package: Do you think this medication is appropriate for you to use?

6. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 6 Purchase Decision  The cost of this medicine is $45 for a bottle of 90 capsules. Would you like to purchase the medicine today?  Information collected: –Reason why did or did not want to purchase orlistat –Height, weight  The cost of this medicine is $45 for a bottle of 90 capsules. Would you like to purchase the medicine today?  Information collected: –Reason why did or did not want to purchase orlistat –Height, weight

7. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 7 TreatmentTreatment  All purchasers initially received an OTC orlistat package containing: –Up to 3 bottles (#90) orlistat, 60 mg –Supplementary educational materials (behavioral and nutritional support) Orlistat User Guide: “How to Lose Weight with Orlistat.”Orlistat User Guide: “How to Lose Weight with Orlistat.” Personal food diaryPersonal food diary Pocket fat gram counterPocket fat gram counter Fat gram wheelFat gram wheel Portion size information cardPortion size information card Orlistat Diet Success Planner:Orlistat Diet Success Planner:  All purchasers initially received an OTC orlistat package containing: –Up to 3 bottles (#90) orlistat, 60 mg –Supplementary educational materials (behavioral and nutritional support) Orlistat User Guide: “How to Lose Weight with Orlistat.”Orlistat User Guide: “How to Lose Weight with Orlistat.” Personal food diaryPersonal food diary Pocket fat gram counterPocket fat gram counter Fat gram wheelFat gram wheel Portion size information cardPortion size information card Orlistat Diet Success Planner:Orlistat Diet Success Planner:

8. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 8 Data collection  Scripted telephone interviews –At about 14, 30, 60, 90, and 104 days after enrollment –Conducted by trained clinical interviewers –Interview content: Started orlistat? Contact with healthcare provider?Started orlistat? Contact with healthcare provider? Use patterns: dose, frequency, timing with foodUse patterns: dose, frequency, timing with food Multivitamin (MVI) useMultivitamin (MVI) use Diet and exerciseDiet and exercise Discomforts? Changes in health or other medicines?Discomforts? Changes in health or other medicines? Weight loss?Weight loss? Use of label, educational materials, websiteUse of label, educational materials, website –Interviews with at least one question answered were included in analysis.  Scripted telephone interviews –At about 14, 30, 60, 90, and 104 days after enrollment –Conducted by trained clinical interviewers –Interview content: Started orlistat? Contact with healthcare provider?Started orlistat? Contact with healthcare provider? Use patterns: dose, frequency, timing with foodUse patterns: dose, frequency, timing with food Multivitamin (MVI) useMultivitamin (MVI) use Diet and exerciseDiet and exercise Discomforts? Changes in health or other medicines?Discomforts? Changes in health or other medicines? Weight loss?Weight loss? Use of label, educational materials, websiteUse of label, educational materials, website –Interviews with at least one question answered were included in analysis.

9. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 9 Data collection  Pharmacy visits –Subjects could return to pharmacy as needed to purchase more orlistat (up to 3 bottles at a time) –One pharmacy visit required after enrollment, time unspecified –Information collected: Drug log form: dates, amount of drug purchasedDrug log form: dates, amount of drug purchased Weight measuredWeight measured Adverse events recordedAdverse events recorded  Pharmacy visits –Subjects could return to pharmacy as needed to purchase more orlistat (up to 3 bottles at a time) –One pharmacy visit required after enrollment, time unspecified –Information collected: Drug log form: dates, amount of drug purchasedDrug log form: dates, amount of drug purchased Weight measuredWeight measured Adverse events recordedAdverse events recorded

10. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 10 AUS Design: Comments  The Drug Facts label and supplementary educational materials used are similar to those submitted to the NDA; however, –some elements of Drug Facts are different in content or location –the actual educational materials submitted to the NDA were not tested.  Objective weight measurements were not required at the end of the study.  Subject diaries were not analyzed or collected.  Some telephone interactions may have influenced subject orlistat use behaviors.  No assessment of discontinuation of use.  90 day AUS. Proposed duration of orlistat use: 6 months.  The Drug Facts label and supplementary educational materials used are similar to those submitted to the NDA; however, –some elements of Drug Facts are different in content or location –the actual educational materials submitted to the NDA were not tested.  Objective weight measurements were not required at the end of the study.  Subject diaries were not analyzed or collected.  Some telephone interactions may have influenced subject orlistat use behaviors.  No assessment of discontinuation of use.  90 day AUS. Proposed duration of orlistat use: 6 months.

11. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 11 Actual Use Study Results

12. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 12 Disposition of Subjects 703 Screened subjects 681 Eligible subjects 543 answer “YES” Regardless of self-selection decision, all eligible subjects: Take REALM test Provide demographic and health history information 22 subjects protocol violation Yes No Eligible for analysis? Yes No “Do you think this medicine is appropriate for you to use?” 52 No 86 Don’t know At one pharmacy site, subjects were given information at enrollment that potentially biased the self-selection process.

13. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 13 Disposition of Subjects (cont.) 681 Eligible subjects 339 Want to purchase 262* Purchasers 261 No 66 Don’t know 15 missing Yes No Would you like to purchase the medicine today? Yes No Subject met inclusion/ exclusion criteria? 49 did not 49 did not meet criteria 237 Evaluable users Yes No Subject used orlistat and completed an interview? 7 did not use 18 no interview 28 did not purchase All 22 subjects excluded for protocol violations purchased orlistat, 21 used it.

14. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 14 Who enrolled? Who used orlistat? The AUS study population Demographic Eligible (N = 681) Users (N = 237) Gender Female 79.4%86% Mean age (years) 45.444.9 Age range (years) 18 – 85 18 – 75 Mean BMI (kg/m 2 ) 33.1 ± 6.7 32.0 ± 5.8 BMI range (kg/m 2 ) 20.9 – 62.6 21 - 53 Ethnicity Caucasian Hispanic Hispanic African American African American79.3%8.1%6.2%82%6%3% Education beyond high school 76.5%84.4% REALM test score Low literate (score ≤ 60) Low literate (score ≤ 60) Literate, > 8 th grade (score > 60) Literate, > 8 th grade (score > 60)8.1%91.5%4.2%95.8%

15. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 15 Correct self-selection responses  Subject meets a condition listed in Drug Facts Warnings under “Do Not Use”: –No, this medicine is not appropriate for me to use.  Subject meets a condition listed in Drug Facts Warnings under “Ask a doctor before use” or “Ask a doctor or pharmacist before use”: –No, this medicine is not appropriate for me to use. –Yes (or Don’t Know), but I need to check with my doctor first.  Subject meets a condition listed in Drug Facts Warnings under “Do Not Use”: –No, this medicine is not appropriate for me to use.  Subject meets a condition listed in Drug Facts Warnings under “Ask a doctor before use” or “Ask a doctor or pharmacist before use”: –No, this medicine is not appropriate for me to use. –Yes (or Don’t Know), but I need to check with my doctor first.

16. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 16 Drug Facts Label Comparison Orlistat OTC Label  Allergy to ingredients  Taking cyclosporine  Diagnosed with problems absorbing food  Not overweight  Gallbladder problems  Kidney stones  Taking diabetes medicine  Taking warfarin  Taking other weight loss drugs Orlistat OTC Label  Allergy to ingredients  Taking cyclosporine  Diagnosed with problems absorbing food  Not overweight  Gallbladder problems  Kidney stones  Taking diabetes medicine  Taking warfarin  Taking other weight loss drugs Actual Use Study Label  Allergy to ingredients  Taking cyclosporine  Taking warfarin  Taking prescription diabetes medicine  Problems absorbing food  Gallbladder problems  More than 30 lbs to lose  Given diet by doctor  Diabetes  High blood pressure  High cholesterol/triglycerides  Taking medicine for high blood pressure or high cholesterol/triglycerides  Taking other weight loss medicine or supplement DoNotUse AskDoctorBeforeUse AskDoctor/Pharm.BeforeUse

17. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 17 Self-selectionSelf-selection  Correct self-selection: 107 + 209 = 316  46.4% of all eligible subjects made a correct self-selection decision  Correct self-selection: 107 + 209 = 316  46.4% of all eligible subjects made a correct self-selection decision 681 Eligible subjects 216 No labeled exclusions 465 Labeled exclusion 7 Self-selected incorrectly209 Self-selected correctly 358 Self-selected incorrectly 107 Self-selected correctly

18. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 18 AUS self-selection decisions: “Do Not Use” AUS label exclusion Subjects w/ exclusion Correct self-selection decisions NumberPercentage Allergic to ingredients 0-- Taking cyclosporine 2 150 Taking warfarin 14750 Taking diabetes medicine 461635

19. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 19 AUS self-selection decisions: “Ask before use” warnings AUS label exclusion Subjects w/ exclusion % correct self selection Problems absorbing food 1217 Gallbladder problems 2540 High blood pressure 16644 High cholesterol/triglycerides 14746 More than 30 lbs to lose 34621 Taking a weight loss medicine 3312 On doctor-recommended diet 4854 NDA label warnings not tested in actual use study: –“Do not use” if you are not overweight –“Ask before use” if you have kidney stones

20. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 20 Purchase decision Purchase decision  Of 631 eligible subjects, 284 purchased orlistat.  Cost was the primary reason that most subjects (60%) did not want to purchase.  17% of those uncertain about purchasing cited a need to speak with a healthcare provider first.  Of 631 eligible subjects, 284 purchased orlistat.  Cost was the primary reason that most subjects (60%) did not want to purchase.  17% of those uncertain about purchasing cited a need to speak with a healthcare provider first.

21. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 21 Baseline BMI and perceptions of body weight Baseline BMI for orlistat users BMI (kg/m 2 ) Users (N = 237) 21 – 24.9 18 (8%) 25 – 29.9 76 (32%) ≥30 143 (60%) Subject self perceptions of body weight Subject responses Users (N = 237) Slightly/moderately underweight 2% Average for height and weight 0 Mildly/moderately overweight 81% Severely overweight 17%

22. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 22 Correct use decisions:  % subjects making correct use decisions –based on self-report at telephone interviews –Contact with healthcare provider was not confirmed.  % subjects making correct use decisions –based on self-report at telephone interviews –Contact with healthcare provider was not confirmed. AUS label exclusion # subjects w/ condition # purchasers w/ exclusion Appropriate use Decision (%) Problems absorbing food 1210 Gallbladder problems 25729 High blood pressure 1665439 High cholesterol/triglycerides 1474943 More than 30 lbs to lose 34611424 Taking a weight loss medicine 331050 On diet recommended by doctor 481225

23. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 23 Typical subject use behaviors (N = 237) Parameter % of subjects interviewed Day 14 (N = 217) Day 30 (N = 219) Day 60 (N = 197) Day 90 (N = 148) Average capsules per dose 0 – 2 more99.1097.30.598.5096.70.7 Average doses per day 0 – 3 more97.81.896.91.898.00.597.30 Average capsules per day 0 – 6 more99.2098.1098.0096.60.7 Taking orlistat with meals 97969895 Still using orlistat 87866346

24. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 24 Multivitamin (MVI) use among orlistat users (N = 237) during the AUS Pattern of MVI use by subjects Telephone interview Day 14 (N = 217) Day 30 (N = 219) Day 60 (N = 197) Day 90 (N = 148) Currently using MVI 163 (75.1%) 178 (81.3%) 163 (82.7%) 127 (85.8%) Taking MVI daily or more than once daily 156 (71.9%) 173 (79.0%) 158 (80.2%) 120 (81.1%) Taking MVI at least 2 hours before or after orlistat 83 (38.2%) 98 (44.7%) 88 (44.7%) 79 (53.4%)

25. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 25 Multivitamin Use: Comments  MVI directions in Drug Facts: –AUS label: Other Information –NDA label: Directions.  LC study results: –73% correct: How to time MVI correctly with orlistat.  Factors potentially influencing compliance: –Label comprehension –Conflicting label directions for MVI use with food  MVI directions in Drug Facts: –AUS label: Other Information –NDA label: Directions.  LC study results: –73% correct: How to time MVI correctly with orlistat.  Factors potentially influencing compliance: –Label comprehension –Conflicting label directions for MVI use with food

26. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 26 Use of educational materials Educational material % subjects using material % subjects who found material useful Fat Counter 6486 Fat Wheel 4679 Personal food diary 4280 Orlistat user guide 4285 Diet success planner 3177

27. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 27 Self-Reported Dietary Behavior Dietary behavior Interview data Day 14 (N = 217) Day 30 (N = 219) Day 60 (n = 197) Day 90 (N = 148) Following any kind of diet 80%69%58%61% Reduced calorie diet 43%41%33%36% Reduced fat diet 78%76%70%66% Somewhat or very successful staying on diet 95%96%98%97%

28. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 28 Weight loss efficacy  Weight loss was a secondary study endpoint  Self-reported weights collected telephone interviews. –Weight change was documented only for subjects who lost weight.  Objective weight measurements collected at enrollment and return pharmacy visits. –Only one return pharmacy visit was required at an unspecified time.  Weight loss was a secondary study endpoint  Self-reported weights collected telephone interviews. –Weight change was documented only for subjects who lost weight.  Objective weight measurements collected at enrollment and return pharmacy visits. –Only one return pharmacy visit was required at an unspecified time.

29. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 29 % Body weight lost % body weight lost Measured weight Day 61 – 90 (N = 60) > 0 – 5% 75% > 5% 42% > 10% 5%

30. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 30 Baseline BMI (kg/m 2 ) Number of subjects Median weight loss (lbs) Range of weight change (lbs) < 2561.5+3 to -7 25 – 29.9284.5+6 to -19 ≥ 30726.5+8 to -52 Total1066.0+8 to -52 Measured weight loss and baseline BMI (Pharmacy visit Days 61 – 90)

31. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 31 Actual Use Study Adverse Events (AEs)

32. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 32 Safety Population (N = 284)  The safety population included at least 8 subjects (and as many as 26 subjects) who did not use orlistat.  2 severe AEs possibly related to study drug: –One case of esophageal spasm –One case of abdominal pain with chronic anemia.  43 subjects experienced 65 adverse events that led to premature study discontinuation –12 non-gastrointestinal adverse events –53 gastrointestinal adverse events typically associated with orlistat use.  The safety population included at least 8 subjects (and as many as 26 subjects) who did not use orlistat.  2 severe AEs possibly related to study drug: –One case of esophageal spasm –One case of abdominal pain with chronic anemia.  43 subjects experienced 65 adverse events that led to premature study discontinuation –12 non-gastrointestinal adverse events –53 gastrointestinal adverse events typically associated with orlistat use.

33. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 33 Common GI Adverse events  Decreased defecation (4.9%)  Soft stools (4.2%)  Nausea (3.9%)  Abdominal distension (3.5%)  Abdominal pain, upper (3.5%)  Dyspepsia (1.8%)  Constipation (1.4%)  Hemorrhoids (1.4%)  Vomiting (1.1%)  Decreased defecation (4.9%)  Soft stools (4.2%)  Nausea (3.9%)  Abdominal distension (3.5%)  Abdominal pain, upper (3.5%)  Dyspepsia (1.8%)  Constipation (1.4%)  Hemorrhoids (1.4%)  Vomiting (1.1%)  Abdominal pain (15.1%)  Oily spotting (13.4%)  Fecal urgency (12.7%)  Flatulence (12.7%)  Liquid stools (10.9%)  Flatus with discharge (10.6%)  Fecal incontinence (8.1%)  Fatty/oily stool (7.0%)  Oily evacuation (7.0%)  Increased defecation (5.3%)

34. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 34 Actual Use Study Answers and Conclusions

35. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 35 Answers to our questions:  Who will use orlistat OTC? –92% of orlistat users were overweight or obese. –Compared to the American population, the study population under-represented consumers of low literacy and non-Caucasian ethnicity. This may or may not accurately reflect consumers likely to use orlistat OTC.This may or may not accurately reflect consumers likely to use orlistat OTC.  Who will use orlistat OTC? –92% of orlistat users were overweight or obese. –Compared to the American population, the study population under-represented consumers of low literacy and non-Caucasian ethnicity. This may or may not accurately reflect consumers likely to use orlistat OTC.This may or may not accurately reflect consumers likely to use orlistat OTC.

36. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 36 Answers to our questions (cont.):  Do subjects correctly choose to use or not use orlistat OTC based on label warnings and indications? –1 of 2 subjects taking cyclosporine and 7 of 14 subjects taking warfarin incorrectly self-selected. –Overall, 46% of eligible subjects self-selected correctly. –GSK conducted 3 self-selection studies focused on cyclosporine and warfarin users and teens. Studies not submitted to FDA.  Do subjects correctly choose to use or not use orlistat OTC based on label warnings and indications? –1 of 2 subjects taking cyclosporine and 7 of 14 subjects taking warfarin incorrectly self-selected. –Overall, 46% of eligible subjects self-selected correctly. –GSK conducted 3 self-selection studies focused on cyclosporine and warfarin users and teens. Studies not submitted to FDA.

37. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 37 Answers to our questions (cont.):  Do subjects dose orlistat correctly? –Yes. Subjects dosed orlistat according to labeled directions throughout the study. –Most subjects followed a diet plan. As labeled, most used a low-fat and/or reduced-calorie diet.  Do subjects lose weight using orlistat OTC? –The data suggest that 75% of subjects lost some weight, and 40% lost more than 5% body weight.  Do subjects dose orlistat correctly? –Yes. Subjects dosed orlistat according to labeled directions throughout the study. –Most subjects followed a diet plan. As labeled, most used a low-fat and/or reduced-calorie diet.  Do subjects lose weight using orlistat OTC? –The data suggest that 75% of subjects lost some weight, and 40% lost more than 5% body weight.

38. Joint Meeting of the Nonprescription Drugs Advisory Committee And Endocrinologic and Metabolic Drugs Advisory Committee January 23, 2006 38 Answers to our questions (cont.):  Are there safety concerns? –Do subjects take a multivitamin correctly while using orlistat? 38 – 53% of users used a MVI according to label directions during the study.38 – 53% of users used a MVI according to label directions during the study. –Do non overweight subjects choose to use orlistat? 7.6% of users had a normal baseline BMI. No underweight individuals enrolled.7.6% of users had a normal baseline BMI. No underweight individuals enrolled. –Are there unexpected adverse events with orlistat use in the OTC environment? No.No.  Are there safety concerns? –Do subjects take a multivitamin correctly while using orlistat? 38 – 53% of users used a MVI according to label directions during the study.38 – 53% of users used a MVI according to label directions during the study. –Do non overweight subjects choose to use orlistat? 7.6% of users had a normal baseline BMI. No underweight individuals enrolled.7.6% of users had a normal baseline BMI. No underweight individuals enrolled. –Are there unexpected adverse events with orlistat use in the OTC environment? No.No.