Actual Use and Compliance Study Of Ibuprofen 600 Mg Immediate Release/Extended Release Tablets In At-Risk OTC Consumers

Study Overview
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Brief Summary
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This will be an open-label, multicenter, 30-day, unsupervised AUS among targeted (at-risk) adult and adolescent consumers designed to mimic an OTC-like environment. More specifically, at-risk consumers, as discussed with the FDA, will comprise elderly consumers (>65 years of age), consumers with an increased risk of gastrointestinal (GI) bleeding or cardiovascular (CV) adverse events, consumers who experience severe pain, low literacy subjects, and adolescents (12-17 years of age). The total number of subjects expected to enroll into the study is approximately 820. Sites will be pharmacies in diverse geographic locations around the US. Prospective adult subjects will be recruited via general population and targeted risk condition advertising (although participants will not be informed as to specific health conditions for which they are being recruited), while adolescents will be recruited using targeted, outbound pre-recruiting telephone calls. Subjects (or the parents/guardians of prospective adolescent subjects) responding to the advertisements or recruitment calls will be initially screened by telephone, and eligibility will subsequently be verified in-person at the pharmacy site.

Official Title
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MULTICENTER ACTUAL USE AND COMPLIANCE STUDY OF IBUPROFEN 600 MG IMMEDIATE RELEASE/EXTENDED RELEASE TABLETS AMONG TARGETED (AT-RISK) CONSUMERS IN A SIMULATED OVER-THE-COUNTER ENVIRONMENT

Conditions
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Pain

Intervention / Treatment
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* Drug: Ibuprofen 600 mg Immediate Release/Extended Release Caplet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: Male or female 18 years of age or older, has history of using oral OTC analgesics at OTC dose levels, defined as taking at least 5 doses/month on average during the past 3 months, and qualifies for inclusion in at least one risk group category, including cardiovascular, gastrointestinal bleeding, history of severe pain (≥5 episodes in last month) or >65 years of age (see Groups 1 4 in Section 3.1). OR Male or female 12-17 years of age and has history of using oral OTC analgesics at OTC dose levels, defined as taking at least 5 doses/month on average during the past 3 months. Evidence of a personally signed and dated informed consent document (ICD), and in the case of minor adolescent subjects (12-17 years of age or adolescent subjects residing in states where the age of majority is > than 18), an assent document, indicating that the subject and where applicable a legally acceptable representative/parent(s)/legal guardian has been informed of all pertinent aspects of the study. Willing and able to comply with scheduled visits, treatment plan, and other study procedures. Willing (or in the case of adolescent subjects, the parent/guardian is willing) and able to purchase study medication. Agrees the product purchased is for subject's own use and not to be shared. Willing (or in the case of adolescent subjects, the parent/guardian is willing) and able to provide contact information for follow up purposes. Exclusion Criteria Subjects with any of the following characteristics/conditions will not be included in the study: Subject (or parent/guardian, if applicable) cannot read, speak, and/or understand English. Trained or employed as a healthcare professional. Subject or someone else in the household is employed by a pharmaceutical company, medical practice or hospital, pharmacy, managed care or health insurance organization or a contract research organization. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or potential subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study. Participation in other studies involving investigational drug(s) within 6 months prior to study entry and/or during study participation. Known hypersensitivity to ibuprofen, aspirin, or any other NSAIDs. Subjects with the following clinical conditions which place them at excessively high risk or have ≥20% 10 year risk for atherosclerotic cardiovascular disease (ASCVD), as defined by the 2013 ACC/AHA Guidelines on the Assessment of Atherosclerotic Cardiovascular Risk, will not be included in the study: clinically established coronary heart disease; cerebrovascular disease; peripheral artery disease; abdominal aortic aneurysm; and chronic kidney disease. Subjects who have experienced a prior non fatal cardiovascular disease event (angina, heart failure, heart disease, heart attack, stroke/transient ischemic attack) or have had heart surgery or who currently have uncontrolled high blood pressure (either by self report or by measured systolic blood pressure higher than 180 mmHg or diastolic pressure higher than 120 mmHg at the time of the enrollment interview), will also be excluded from the study. Subjects with concurrent or recent (within 30 days) use of anticoagulants, a prior history of complicated peptic ulcer, or a gastrointestinal bleeding event requiring hospitalization or blood transfusion. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product (IP) administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. Pregnant female subjects; breastfeeding female subjects; and male and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for 28 days after the end of their 30-Day Use Phase or, for subjects who use the investigational product after Day 30, 28 days after the last recorded dose of investigational product. 18 years of age or older and classified as normal literacy (REALM Test score ≥61) after the normal literacy group quotas (approximately 70% of adult subjects) are full or refuses to complete the REALM Test (note there is no corresponding literacy exclusion criterion for adolescent subjects based on REALM Teen score). 18 years of age or older and classified as moderate (less frequent) oral OTC pain reliever user (<30 doses per month on average in the preceding 3 months) after the moderate user group quotas (approximately 33% of adult subjects) are full. Not capable of swallowing a vitamin sized tablet. Refuses to participate in required assessments (such as urine pregnancy, finger stick cholesterol or blood pressure tests, or unable or unwilling to comply with electronic diary procedures). The following additional exclusion criteria will be applied for adolescent subjects only (12-17 years of age): Has developmental or learning disabilities that, in the judgment of the parent/guardian or the investigator, would interfere with study participation. Another adolescent child from the family is already enrolled into the study, or parent/guardian does not agree that only one adolescent child from the family or household will be enrolled into the study.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Parallel Assignment
Interventional Model Description: The Actual Use Trial (AUT) design utilizes a real world setting to assess the ability of consumers to use an investigational product that will be marketed in an over-the-counter setting according to the proposed product labelling. The primary objective of this AUT is to evaluate compliance with the labeled dosing directions for Advil 12 Hour and to understand why misuse occurred and if it was a conscious decision by the subject. A secondary objective is to evaluate the safety of Advil 12 Hour in unsupervised actual use and how it relates to misuse.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ibuprofen 600 mg Immediate Release/Extended Release Tablets<br>Ibuprofen 600 mg Immediate Release/Extended Release Tablets | Drug: Ibuprofen 600 mg Immediate Release/Extended Release Caplet<br>* Ibuprofen 600 mg Immediate Release/Extended Release Tablet to be adminstered orally (i.e., one caplet every 12 hours, not to exceed 2 caplets per day) for pain.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Data Analysis Set 1 Exceeding the Maximum Daily Dose of 1200 mg on 2 or More Calendar Days During the Use Period | Use period was defined as 30 days from purchase. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 2 Exceeding the Maximum Daily Dose of 1200 mg on 2 or More Calendar Days During the Use Period | Use period was defined as 30 days from purchase. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 3 Exceeding the Maximum Daily Dose of 1200 mg on 2 or More Calendar Days During the Use Period | Use period was defined as 30 days from purchase. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 4 Exceeding the Maximum Daily Dose of 1200 mg on 2 or More Calendar Days During the Use Period | Use period was defined as 30 days from purchase. | From first purchase of study drug (Day 1) to Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Data Analysis Set 1 Exceeding the Maximum Daily Dose of 1200 mg on 1 or More Calendar Days During the Use Period | Use period was defined as 30 days from purchase. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 2 Exceeding the Maximum Daily Dose of 1200 mg on 1 or More Calendar Days During the Use Period | Use period was defined as 30 days from purchase. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 3 Exceeding the Maximum Daily Dose of 1200 mg on 1 or More Calendar Days During the Use Period | Use period was defined as 30 days from purchase. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 4 Exceeding the Maximum Daily Dose of 1200 mg on 1 or More Calendar Days During the Use Period | Use period was defined as 30 days from purchase. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 1 Exceeding the Maximum Daily Dose of 1200 mg on 1 or More Calendar Days During Use Period Due to Unintentional Misuse | Unintentional misuse: Participants who did not understand the dosing instructions on the package. Use period was defined as 30 days from purchase. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 2 Exceeding the Maximum Daily Dose of 1200 mg on 1 or More Calendar Days During Use Period Due to Unintentional Misuse | Unintentional misuse: Participants who did not understand the dosing instructions on the package. Use period was defined as 30 days from purchase. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 3 Exceeding the Maximum Daily Dose of 1200 mg on 1 or More Calendar Days During Use Period Due to Unintentional Misuse | Unintentional misuse: Participants who did not understand the dosing instructions on the package. Use period was defined as 30 days from purchase. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 4 Exceeding the Maximum Daily Dose of 1200 mg on 1 or More Calendar Days During Use Period Due to Unintentional Misuse | Unintentional misuse: Participants who did not understand the dosing instructions on the package. Use period was defined as 30 days from purchase. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 1 Exceeding the Maximum Amount Per Dose of 600 mg on 1 or More Occasions |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 2 Exceeding the Maximum Amount Per Dose of 600 mg on 1 or More Occasions |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 3 Exceeding the Maximum Amount Per Dose of 600 mg on 1 or More Occasions |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 4 Exceeding the Maximum Amount Per Dose of 600 mg on 1 or More Occasions |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 1 Exceeding the Maximum Amount Per Dose of 600 mg on 2 or More Occasions |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 2 Exceeding the Maximum Amount Per Dose of 600 mg on 2 or More Occasions |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 3 Exceeding the Maximum Amount Per Dose of 600 mg on 2 or More Occasions |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 4 Exceeding the Maximum Amount Per Dose of 600 mg on 2 or More Occasions |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 1 Exceeding the Maximum Daily Dose of 1200 mg on 10 or More Calendar Days | Participants did not need to necessarily use the study medication for 10 consecutive days. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 2 Exceeding the Maximum Daily Dose of 1200 mg on 10 or More Calendar Days | Participants did not need to necessarily use the study medication for 10 consecutive days. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 3 Exceeding the Maximum Daily Dose of 1200 mg on 10 or More Calendar Days | Participants did not need to necessarily use the study medication for 10 consecutive days. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 4 Exceeding the Maximum Daily Dose of 1200 mg on 10 or More Calendar Days | Participants did not need to necessarily use the study medication for 10 consecutive days. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 1 Exceeding the Maximum Daily Dose of 1200 mg on 7 or More Calendar Days | Participants did not need to necessarily use the study medication for 7 consecutive days. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 2 Exceeding the Maximum Daily Dose of 1200 mg on 7 or More Calendar Days | Participants did not need to necessarily use the study medication for 7 consecutive days. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 3 Exceeding the Maximum Daily Dose of 1200 mg on 7 or More Calendar Days | Participants did not need to necessarily use the study medication for 7 consecutive days. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 4 Exceeding the Maximum Daily Dose of 1200 mg on 7 or More Calendar Days | Participants did not need to necessarily use the study medication for 7 consecutive days. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 1 Who Took More Than 2 Doses on a Calendar Day | More than 2 doses on a calendar day means more than 2 dosing occasions on a calendar day. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 2 Who Took More Than 2 Doses on a Calendar Day | More than 2 doses on a calendar day means more than 2 dosing occasions on a calendar day. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 3 Who Took More Than 2 Doses on a Calendar Day | More than 2 doses on a calendar day means more than 2 dosing occasions on a calendar day. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 4 Who Took More Than 2 Doses on a Calendar Day | More than 2 doses on a calendar day means more than 2 dosing occasions on a calendar day. | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 1 Who Re-dosed in Less Than (<)12 Hours, <10 Hours and <8 Hours on 1 or More Occasions |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 2 Who Re-dosed in Less Than (<)12 Hours, <10 Hours and <8 Hours on 1 or More Occasions |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 3 Who Re-dosed in Less Than (<)12 Hours, <10 Hours and <8 Hours on 1 or More Occasions |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 4 Who Re-dosed in Less Than (<)12 Hours, <10 Hours and <8 Hours on 1 or More Occasions |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 1 Who Used the Product on More Than 10 Consecutive Calendar Days |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 2 Who Used the Product on More Than 10 Consecutive Calendar Days |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 3 Who Used the Product on More Than 10 Consecutive Calendar Days |  | From first purchase of study drug (Day 1) to Day 30 | 
| Percentage of Participants in Data Analysis Set 4 Who Used the Product on More Than 10 Consecutive Calendar Days |  | From first purchase of study drug (Day 1) to Day 30 |