Clinical Trial Results:
An Open Label, Actual Use Study in Consumers Taking an Extended-Release Over-the-Counter NSAID in a Naturalistic Setting
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Summary
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EudraCT number |
2014-005268-13 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
14 Nov 2008
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Results information
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Results version number |
v2(current) |
This version publication date |
07 Sep 2016
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First version publication date |
15 Jul 2015
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BAYH6689/13129
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00751400 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Bayer AG
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Sponsor organisation address |
Kaiser-Wilhelm-Allee, D-51368, Leverkusen, Germany,
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Public contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Scientific contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Nov 2008
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Nov 2008
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess subjects’ patterns of use of the extended release (ER) naproxen sodium product.
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects and/or their legally authorized representative. Participating subjects and/or their legally authorized representative signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Jul 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 562
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Worldwide total number of subjects |
562
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
2
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Adults (18-64 years) |
444
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From 65 to 84 years |
109
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85 years and over |
7
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Recruitment
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Recruitment details |
Recruitment for the study was conducted using newspaper ads, direct mailing, in-store pharmacy posters, and flyers. Potential subjects who learned about the study through local advertising were directed to call a toll-free number (call center at the contract research organization [CRO]) where minimal screening questions were asked. | ||||||||||||||||
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Pre-assignment
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Screening details |
Once at the pharmacy, if the screening criteria were met, subjects were given an (empty) over-the-counter (OTC) package and were allowed as much time as needed to review the label. They were then told the cost of the investigational product and asked if they would like to purchase it for their own use. | ||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Naproxen Sodium ER (BAYH6689) | ||||||||||||||||
Arm description |
Subjects received 1 tablet of naproxen sodium ER every 24 hours while symptoms lasted for no more than 10 consecutive days for pain and no more than 3 consecutive days for fever. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Naproxen Sodium ER
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Investigational medicinal product code |
BAYH6689
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received 1 tablet of naproxen sodium ER every 24 hours while symptoms lasted for no more than 10 consecutive days for pain and no more than 3 consecutive days for fever.
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| Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: A few subjects had used product outside of both 5-day interview windows but considered as study completers (subjects who completed at least 1 interview), as planned. Hence, the number of subjects at this milestone differs with the number of subjects in the arm. [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: A few subjects did not use study product but considered as study completers (subjects who completed at least 1 interview), as planned. Hence, the number of subjects at this milestone differs with the number of subjects in the arm. |
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Baseline characteristics reporting groups [1]
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Reporting group title |
Naproxen Sodium ER (BAYH6689)
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Reporting group description |
Subjects received 1 tablet of naproxen sodium ER every 24 hours while symptoms lasted for no more than 10 consecutive days for pain and no more than 3 consecutive days for fever. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same. Justification: Not all the enrolled subjects were provided with study drugs. As baseline included only subjects who were provided with the study drug, the worldwide number enrolled in the trial differs with the number of subjects reported in the baseline period. |
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End points reporting groups
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Reporting group title |
Naproxen Sodium ER (BAYH6689)
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Reporting group description |
Subjects received 1 tablet of naproxen sodium ER every 24 hours while symptoms lasted for no more than 10 consecutive days for pain and no more than 3 consecutive days for fever. | ||
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End point title |
Use Days With One or More Misuse Occasions [1] | ||||||||||
End point description |
Misuse occasion: any reported use of 2 or more tablets within a 22 hour period (included use of 2 tablets in 1 dose or the use of 1 tablet at one time and 1+ tablets at a later time within the same 22 hour period). Use-days were calculated based on days in which there was subject-reported product consumption, meaning that if a tablet was consumed on a day this resulted in 1 use-day. If a subject reported product consumption on 3 different days this resulted in 3 use-days. The cumulative expression of use-days is the total number of use-days reported by all subjects with follow up data. Here, "Number of subjects analysed" reflects subjects that completed at least one interview and provided use information for the previous 5 days.
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End point type |
Primary
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End point timeframe |
1 month
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Dosing Occasions With One and More Than One Tablet Taken | ||||||||||||
End point description |
Dosing occasion means a single occasion in which a subject reported consuming the study drug. Multiple dosing occasions were possible throughout one use-day. For example, if a subject took one tablet at 6 anti-meridian (am), this would result in one dosing occasion. If the same subject took one tablet later that same day at 8 post-meridian (pm), this would result in a second dosing occasion. Here, "Number of subjects analysed" reflects subjects that completed at least one interview and provided use information for the previous 5 days.
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End point type |
Secondary
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End point timeframe |
1 month
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Use Days With and Without Next Dose Less Than 22 Hours Later | ||||||||||||
End point description |
Use-days were calculated based on days in which there was subject-reported product consumption, meaning that if a tablet was consumed on a day this resulted in one use-day. If a subject reported product consumption on three different days this resulted in three use-days. The cumulative expression of use-days is the total number of use-days reported by all subjects with follow up data. Here, "Number of subjects analysed" reflects subjects that completed at least one interview and provided use information for the previous 5 days.
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End point type |
Secondary
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End point timeframe |
1 month
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Subjects With and Without More Than One Tablet Taken Per Dose | ||||||||||
End point description |
Here, "Number of subjects analysed" reflects subjects that completed at least one interview and provided use information for the previous 5 days.
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End point type |
Secondary
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End point timeframe |
1 month
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of Subjects With and Without Next Dose Less Than 22 Hours Later | ||||||||||
End point description |
This endpoint is a measure of subjects while endpoint titled "Use Days With and Without Next Dose Less Than 22 Hours Later" provides the outcome as a measure of cumulative number of use-days for all subjects involved. Here, "Number of subjects analysed" reflects subjects that completed at least one interview and provided use information for the previous 5 days.
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End point type |
Secondary
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End point timeframe |
1 month
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of Subjects With and Without More Than 660 milligram (mg) at Least Once | ||||||||||
End point description |
This measure refers to number of subjects that exceeded 660 mg of naproxen sodium per day at least once during the reporting period. The maximum dose (660 mg) may have been exceeded with one dose (if a subject consumed two tablets in one dosing occasion) or may have been exceeded throughout the course of a use-day (if a subject took one tablet in one dosing occasion and then later in the same day took one or more tablets in another dosing occasion). Here, "Number of subjects analysed" reflects subjects that completed at least one interview and provided use information for the previous 5 days.
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End point type |
Secondary
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End point timeframe |
1 month
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| No statistical analyses for this end point | |||||||||||
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End point title |
Average Daily Dose | ||||||||
End point description |
Here, "Number of subjects analysed" reflects subjects that completed at least one interview and provided use information for the previous 5 days.
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End point type |
Secondary
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End point timeframe |
1 month
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Subjects That Have Taken Study Drug on More Than 10 Consecutive Days and Not on More Than 10 Consecutive Days | ||||||||||
End point description |
This endpoint is reporting how many subjects exceeded the label limit for consecutive days of study drug dosing. Here, "Number of subjects analysed" reflects number of subjects reporting at least one tablet taken at any point during study.
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End point type |
Secondary
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End point timeframe |
1 month
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of Total Dosing Occasions Per Subject | ||||||||
End point description |
Dosing occasion means a single occasion in which a subject reported consuming the study drug. Multiple dosing occasions were possible throughout one use-day. For example, if a subject took one tablet at 6 am this would result in one dosing occasion. If the same subject took one tablet later that same day at 8 pm this would result in a second dosing occasion. Here, "Number of subjects analysed" reflects subjects that completed at least one interview and provided use information for the previous 5 days.
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End point type |
Secondary
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End point timeframe |
1 month
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Dosing Occasions Per Subject That Exceeded 660 milligram (mg) | ||||||||
End point description |
Dosing occasion means a single occasion in which a subject reported consuming the study drug. Multiple dosing occasions were possible throughout one use-day. For example, if a subject took one tablet at 6 am this would result in one dosing occasion. If the same subject took one tablet later that same day at 8 pm this would result in a second dosing occasion. Here, "Number of subjects analysed" reflects subjects that completed at least one interview and provided use information for the previous 5 days.
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End point type |
Secondary
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End point timeframe |
1 month
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the date of informed consent signed until the end of 28-day follow-up period
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.1
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Reporting groups
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Reporting group title |
Naproxen Sodium ER (BAYH6689)
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Reporting group description |
Single dose (1 tablet) of naproxen sodium ER 660 mg every 24 hours while symptoms lasted for not more than 10 consecutive days for pain and not more than 3 consecutive days for fever. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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09 Jun 2008 |
The protocol was amended to reflect changes requested by the Food and Drug Administration (FDA).
1. Dose of 440 mg was administered within the first hour
2. Clarified details about periodic follow-up interviews
3. Moderate OTC analgesic users had self-reported taking at least 5 doses per month
4. Study was conducted in 3 parts: screening, enrolment and use phase, and clarifications were provided on these phases
5. Tracking of recruitment was briefly explained
6. Subjects who had inquired about the study were excluded in the enrolment phase if they had participated in an OTC analgesic-related study in the last 12 months, healthcare and related professionals, history of known allergies to non-steroidal antiinflammatory drugs, heart surgery in the last 60 days or plans for it in the next 60 days, female pregnant or breast-feeding
7. Eligibility screener period was included as an assessment period
8. The primary endpoint was updated as the proportion of the total number of use days with a misuse occasion among all use-days in the User population. A cut point of 22 hours had been established in order to account for some variability in the reporting of exact dosing timing by subjects during follow-up interviews.
9. The following secondary endpoints were included: a) average daily dose of naproxen on use days in the user population; b) number/percentage of subjects in the safety population who took Aleve 24 Hour more than 10 consecutive days; c) total number of dosing occasions during use days per subject among the user population. All analyses were performed for the heavy, regular, normal and low literate use cohorts. |
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17 Jun 2008 |
The following statement was included under phone eligibility screener section:
"The purpose of this study was to collect information about how an investigational dose of an approved medication was used by consumers". |
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02 Jul 2008 |
The drug label was updated with revised expiry date and a statement that product might take longer to work if taken with food. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| No control group, detailed data collected for up to 10 days during 1 month follow-up, data recall by subjects may vary. | |||
