Antibiotic plus MucinexD Annotated

Antibiotic + Your guide to the Antibiotic + MUCINEX D Study Detail Aid As part of the Reckitt Benckiser mission to be a leader in respiratory relief, we strive to add value through innovation and build support to ensure the success of our product lines. Delivering new data and proven clinical results is a key focus and will help our products capture and hold the health care community’s interest. MUCINEX D is already one of the best-selling products in the MUCINEX family. Now there’s even more exciting news to help you sell MUCINEX D to health care professionals (HCPs). We are thrilled to provide the results of this innovative clinical study, with data demonstrating that adding MUCINEX D to an antibiotic regimen helps patients feel better faster.

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This rigorously designed study is unique because it examines the benefits of using an over-the-counter (OTC) product (MUCINEX D) for symptom relief as an adjunct to an antibiotic in patients with an ARI. The study demonstrates that MUCINEX D speeds symptom relief while the antibiotic fights the infection.

Antibiotic + MUCINEX D

The Antibiotic + MUCINEX D study is the first and only published placebo-controlled study to examine the benefits of an OTC medicine (MUCINEX D) for symptom relief as an adjunct to an antibiotic in the treatment of acute respiratory infections (ARI).* Placebo control is a key feature of the Antibiotic + MUCINEX D study; including a placebo control group as part of research design helps to ensure validity and credibility of the clinical results.

The Antibiotic + MUCINEX D study gives physicians results proven in a clinical study with a clear message: when you prescribe an antibiotic for an ARI, recommend MUCINEX D as well.

Look inside to start learning more about this exciting clinical study and what it means for selling MUCINEX D!

Insight: You may find that some of your physicians are already recommending MUCINEX D for use with an antibiotic. Data from this study validate this recommending practice. * Based on a search (several databases, including PubMed, as of June 6, 2008) of clinical trials conducted over the past 10 years in which an OTC medication was used as an adjunct to an antibiotic.

Sales representatives: For informational purposes only. Not to be distributed, copied, or used as a selling tool.

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Power Proven in a Clinical Study

The Antibiotic + MUCINEX D Clinical Study ®

How to use this annotated guide to get the most out of every Antibiotic + MUCINEX® D sales call: Use this guide as a reference tool prior to each sales call for MUCINEX D and to reinforce key selling messages.

Focus on the objectives indicated for each page.

Practice your presentations for each section.

Tailor each presentation by concentrating on the most relevant messages for that particular HCP.

The Graphic

Open your sales call to gain interest and engage the HCP.

The Antibiotic + MUCINEX D graphic is a visual cue that reinforces the selling message of adding MUCINEX D to provide relief of respiratory symptoms when prescribing an antibiotic for an ARI.

• S tate your purpose: to give the HCP important clinical information about using MUCINEX D for respiratory symptom relief as an adjunct to antibiotic therapy for an ARI

The Look

During EVERY call

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— State the value of MUCINEX D: it is proven in a clinical study to speed symptom relief when used with an antibiotic to fight an ARI — Check for acceptance: ask for permission to provide more information about adding MUCINEX D to an antibiotic regimen

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Antibiotic + MUCINEX D

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Probe the HCP about both the role of an antibiotic for treating an ARI and the role of MUCINEX D for providing symptom relief for an ARI. • Explore his or her need to speed symptom relief for patients who are taking an antibiotic for an ARI

Support your presentation.

• A cknowledge the HCP’s need: recognize that the HCP would like to offer faster symptom relief to patients with symptoms of an ARI • P resent the results of the Antibiotic + MUCINEX D clinical study, emphasizing that the addition of MUCINEX D to an antibiotic regimen significantly shortens time to relief and improves respiratory symptoms vs an antibiotic alone studied in the trial (see page 7)

The Antibiotic + MUCINEX D study sales aid has a clean, clinical look. The sales aid is simple but impactful, concentrating on 3 visuals—the 2 line graphs and the “5 to 1” claim visual. The visuals deliver 3 key points: • Symptom relief • Patient satisfaction • Physician satisfaction

The Message The message encapsulates the study findings— that taking MUCINEX D with an antibiotic for an ARI helps patients feel better faster.

The message to the physician is simple—“When you prescribe an antibiotic for an ARI, always think antibiotic + MUCINEX D to speed symptom relief while fighting an ARI.”

heck for acceptance: ask whether adding MUCINEX D to an antibiotic regimen for an ARI • C offers the benefits patients are looking for

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close your presentation.

• Summarize the results of the Antibiotic + MUCINEX D clinical study • P ropose next steps: offer a day and time when you plan to return to hear about how MUCINEX D is helping patients with ARI symptoms and gain agreement from the HCP to recommend MUCINEX D for respiratory symptom relief as an adjunct to an antibiotic for the treatment of an ARI • C heck for acceptance: ask the HCP if he or she has any questions and provide any additional information

2 Sales representatives: For informational purposes only. Not to be distributed, copied, or used as a selling tool.

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3 Sales representatives: For informational purposes only. Not to be distributed, copied, or used as a selling tool.

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Help Patients Feel Better Faster

Bring the Clinical Research to Life Objective: Explain the objectives and methodology of the Antibiotic + MUCINEX® D study to underscore the credibility of this carefully designed research study.

Key Messages • Open by stating the overall outcome of the Antibiotic + MUCINEX D clinical study • P oint out that this placebo-controlled research study is the first of its kind to be published.

It examines the clinical benefits of using an OTC medicine (MUCINEX D) for symptom relief as an adjunct to an antibiotic in the treatment of an ARI • E xplain that this study was designed and executed according to rigorous clinical research standards

Understanding the study This was a multicenter study, performed at 30 clinical sites. A total of 601 adult patients participated. Patients were randomized to 2 separate treatment groups: 303 patients received an antibiotic + MUCINEX D and 298 received an antibiotic + placebo. All patients were prescribed an antibiotic regimen determined by the treating physician for an ARI.1 To participate in the study, patients had to: • B e 18 to 75 years of age • Have significant respiratory symptoms (defined as a total symptom score of at least 10, based on a 0 to 3 severity rating) for each of the following: chest congestion, nasal congestion, thickened sputum or phlegm, facial pain/pressure/tenderness, cough, breathlessness, runny nose, sinus headache, sore throat, postnasal drip • Have met the physician’s diagnostic criteria for the prescription of oral antibiotic therapy Exclusion criteria included: • C hronic or recurring medical conditions • Certain medications • Hypersensitivity to study medications Patients were instructed to take 2 tablets of MUCINEX D or matching placebo twice daily, morning and evening, for 7 days. They started taking their medication the evening of Day 1 and recorded their ratings of the 10 respiratory symptoms measured in the study in a daily diary. In addition, patients answered questions for other outcome measures, including “How do you feel today compared to when you started the study medicine?” (worse, the same, better, much better, all better) and “Did you feel that the medication was helping you during the day?” (yes/no).1 Patients returned to their doctor’s office on Day 4 and Day 8 (at the end of treatment). At the final visit, patients rated overall efficacy of the treatment in relieving symptoms, and physicians made a global assessment of the efficacy of the treatment by answering the question, “Based on the observed treatment outcome for this patient, would you recommend the study medication for future use as adjunct therapy with antibiotics for treatment of acute respiratory infections?” (yes/no).1 The percentage of patients who discontinued the study because of adverse events was 5% (15 patients) in the MUCINEX D group and 2.7% (8 patients) in the placebo group.1 [Note: Patients took 2 MUCINEX D tablets (600 mg guaifenesin and 60 mg pseudoephedrine HCl) twice daily. If asked, this is equivalent to 1 Maximum Strength MUCINEX D tablet (1200 mg guaifenesin and 120 mg pseudoephedrine HCl) twice daily.]2,3

Insight: This study design set a high standard for measuring MUCINEX D performance because ALL patients took active medication—an antibiotic + MUCINEX D or an antibiotic + placebo.1 No patient took placebo only.

4 Sales representatives: For informational purposes only. Not to be distributed, copied, or used as a selling tool.

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5 Sales representatives: For informational purposes only. Not to be distributed, copied, or used as a selling tool.

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The Clinical Data Equation

Antibiotic + MUCINEX D = Faster Symptom Relief ®

Objective: Explain that this clinical study proves that adding MUCINEX® D to an antibiotic regimen in patients being treated for an ARI speeds symptom relief vs an antibiotic alone.

Key messages • Point out the key overall symptom relief results of the study • E mphasize that early in the study (Day 3), significant improvement in the total symptom score was seen in patients taking an antibiotic + MUCINEX D vs an antibiotic + placebo.

Patients in the study rated the following 10 respiratory symptoms twice daily*1 ON LABEL2

OFF LABEL

Chest congestion Nasal congestion Thickened sputum or phlegm Facial pain/pressure/tenderness

Cough Breathlessness Runny nose

Sinus headache Postnasal drip Sore throat

Each symptom was rated on a severity scale of 0=none, 1=mild, 2=moderate, and 3=severe.1 The total symptom score was calculated for each patient by day and averaged.

The 10.6 score (antibiotic + MUCINEX D) and the 11.6 score (antibiotic + placebo) are magnified to highlight the clinically significant difference. These numbers demonstrate that patients in the MUCINEX D group rated their symptoms as significantly less severe than patients in the placebo group on Day 3 of the study. * MUCINEX D is approved to: help loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive; temporarily relieve nasal congestion due to common cold, hay fever, upper respiratory allergies; temporarily restore freer breathing through the nose; promote nasal and/or sinus drainage; temporarily relieve sinus congestion and pressure.2

Insight: “P value” or “probability value” is the likelihood of getting positive clinical data/results strictly by chance. P values are used to indicate the statistical significance of the clinical findings. Clinical research results are considered statistically significant if the P value is 0.05 or less.4,5 The lower the P value, the more significant the result is considered to be; ie, the less likely it is to get a positive result by chance.

In this case, the P value is 0.026—around half of the 0.05 cutoff point for statistical significance. So, you can see it’s a strong P value!

MUCINEX D demonstrated significant clinical benefits in the relief of respiratory symptoms.

• R efer to this bullet when/if you are asked about the combined antibiotic + MUCINEX D regimen

Trial Bridging Statement WE’VE REVIEWED CLINICAL FINDINGS that DEMONSTRATE ADDING MUCINEX D TO AN ANTIBIOTIC REGIMEN SIGNIFICANTLY IMPROVES SYMPTOM RELIEF. NOW LET’S TALK ABOUT SYMPTOM RELIEF HELPING PATIENTS DURING THE DAY. 6 Sales representatives: For informational purposes only. Not to be distributed, copied, or used as a selling tool.

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7 Sales representatives: For informational purposes only. Not to be distributed, copied, or used as a selling tool.

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For Relief of ARI Symptoms…

…Patients Prefer Antibiotic + MUCINEX D ®

ObjectivES: 1. Explain that the study clearly demonstrates that physicians and patients agree—both prefer the effectiveness of adding MUCINEX D to an antibiotic regimen for respiratory symptom relief. 2. Gain the physician’s commitment to adding MUCINEX D as an adjunct to an antibiotic for symptom relief in patients with an ARI. Key messages • P oint out that as early as Day 2 of the combined regimen, MUCINEX D made a significant difference in helping patients during the day — This chart illustrates how quickly MUCINEX D started helping patients. Patients were asked, “Did you feel the medication was helping during the day?” and recorded a “yes” or “no” in a daily diary each evening. This question was excluded from Day 1 evening.1 The percentage of patients answering “yes” for each day is plotted in this graph. The 68% (antibiotic + MUCINEX D) and 55% (antibiotic + placebo) are magnified to highlight the clinically significant difference between them. Remember, the lower the P value, the more statistically significant it is, so 0.002 is highly significant!

• P atient preference for antibiotic + MUCINEX D treatment effectiveness measured at the end of the study was also strong. Patients in each group (antibiotic + MUCINEX D and antibiotic + placebo) rated overall efficacy of symptom relief as1: 0=Not effective 1=Somewhat effective 2=Moderately effective 3=Very effective 4=Extremely effective

insight: A higher percentage (44.6%) of patients in the antibiotic + MUCINEX D group rated treatment efficacy as very/extremely effective compared with patients in the antibiotic + placebo group (37.5%). This difference was statistically significant in favor of MUCINEX D (P=0.021).1

• P hysician preference for the combined antibiotic + MUCINEX D regimen is dramatic as well.

At the end of treatment, physicians were asked, “Based on the observed treatment outcome for this patient, would you recommend the study medication for future use as adjunct with antibiotics for the treatment of acute respiratory infection?” and answered “yes” or “no”1 — The number of physicians recommending the antibiotic + MUCINEX D regimen was significantly higher than those recommending the antibiotic + placebo regimen (P=0.048) — For patients on the combined antibiotic + MUCINEX D regimen, physicians answered “yes” 236 times and “no” 51 times, approximately a 5-to-1 ratio

8 Sales representatives: For informational purposes only. Not to be distributed, copied, or used as a selling tool.

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9 Sales representatives: For informational purposes only. Not to be distributed, copied, or used as a selling tool.

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For ARI Symptom Relief

...Physicians Prefer Antibiotic + MUCINEX D ®

Objectives: Highlight the study results and ask for the physician’s commitment to recommend MUCINEX D as an adjunct for respiratory symptom relief to an antibiotic in patients with an ARI.

Key messages • R einforce that recommending MUCINEX D as an adjunct to an antibiotic has significant patient benefits because it speeds symptom relief while the antibiotic fights the infection • Re-emphasize the MUCINEX D brand story

Selling Tip: Leave behind a copy of the Antibiotic + MUCINEX D study DVD

Close “ DO I HAVE YOUR COMMITMENT TO RECOMMEND ADDING MUCINEX D FOR RESPIRATORY SYMPTOM RELIEF TO ANTIBIOTIC THERAPY FOR YOUR PATIENTS WITH AN ACUTE RESPIRATORY INFECTION?”

For complete Drug Facts, visit www.mucinex.com or call 1-866-MUCINEX (1-866-682-4639).

References: 1. Data on file [Antibiotic + Mucinex D clinical study (ITT analysis)], Reckitt Benckiser, Parsippany, NJ. 2. Mucinex D product labeling.

3. Maximum Strength Mucinex D product labeling. 4. Merriam-Webster Web site. http://www.merriam-webster.com/dictionary/P%20value.

Accessed May 29, 2008. 5. Cochrane handbook Web site. Glossary. http:// www.cochrane.dk/cochrane/handbook/glossary. Accessed May 29, 2008.

6. National Cancer Institute Web site. NCI dictionary of cancer terms. http://www.cancer.gov/dictionary. Accessed May 29, 2008. 7. National Institutes of Health. Glossary of clinical trials terms. http://www.clinicaltrials.gov/ct/info/glossary. Accessed May 29, 2008.

10 Sales representatives: For informational purposes only. Not to be distributed, copied, or used as a selling tool.

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11 Sales representatives: For informational purposes only. Not to be distributed, copied, or used as a selling tool.

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Clinical Study Glossary Acute Respiratory Infection (ARI)

Placebo

Any rapid-onset and short-lasting infection of the respiratory tract.

An inactive substance designed to resemble the investigational drug being tested (matching placebo).

A placebo-controlled trial is a trial design in which a placebo is given to 1 group of participants while the investigational drug is given to another group. The results obtained in the 2 groups are then compared to see if the investigational treatment is more effective in treating the condition.

Adverse Event (AE) Any unwanted event experienced by a participant in a clinical trial. An AE can include new symptoms or exacerbation of an existing condition. It may be related or unrelated to the investigational product; if related, it can be termed an adverse drug reaction (ADR).6

Double-Blind Trial A clinical trial design in which NEITHER the participants NOR the study staff know which participants are receiving the investigational drug and which are receiving another therapy or placebo.7

Global Assessment Overall treatment assessment by the investigator at the end of the study.

Intent-to-Treat (ITT) Analysis of clinical trial results that includes all data from participants in the groups to which they were randomized (see randomized trial), even if they only received 1 dose.7

Multicenter Trial A clinical trial involving several investigating institutions. The benefits of multicenter trials include a larger number of participants, different geographic locations, and the possibility of inclusion of a wider range of population groups.

PubMed Search A text-based search and retrieval system for National Library of Medicine databases.

P Value The probability (ranging from 0 to 1) that the results observed in a study could have occurred by chance.

The cutoff for statistical significance is usually taken as 0.05 (see statistical significance).5

Randomized Trial A clinical trial design in which participants are assigned to a study arm based on random chance.

Randomization ensures that no specific criteria are used to assign any participants to a particular group, so all groups will be equally comparable.7

Statistical Significance An estimate of the probability of an effect as large or larger than what is observed by chance, usually expressed as a P value (see P value). A statistically significant result is one that is unlikely to have occurred by chance.5

Parallel-Group Trial A clinical trial design that compares 2 or more groups of participants, 1 of which receives the investigational drug. The other group(s) receive placebo or a standard treatment (see placebo).5

Please see page 11 for references.

Š RBI 2008 1035 REV. 080408 Ž

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