Clinical Trial Results:
An Actual Use Trial In A Simulated OTC Environment of an Extended-Release Over-the-Counter NSAID
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Summary
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EudraCT number |
2014-005316-41 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
28 Dec 2011
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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 |
26 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 |
BAYH6689/15647
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01427803 | ||
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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 Dec 2011
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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 |
28 Dec 2011
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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 |
An actual use trial was designed to demonstrate whether consumers will exceed the labeled daily dose of Aleve 24 Hour at an unacceptable rate. Two aspects of consumer use of Aleve 24 Hour were examined: 1) the frequency at which consumers exceed the label-defined daily dose, thus putting themselves at clinical risk, and 2) the reasons for exceeding the labeled daily dose.
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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 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 |
14 Sep 2011
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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: 778
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Worldwide total number of subjects |
778
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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) |
4
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Adults (18-64 years) |
651
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From 65 to 84 years |
119
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85 years and over |
4
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Recruitment
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Recruitment details |
Thirty two sites in the United States enrolled subjects in the trial between 14 September 2011 (First subject first visit) and 28 December 2011 (Last subject last visit). | |||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
The total 1931 subjects were screened over the telephone, 924 subjects began the enrollment interview, 778 subjects were randomized, and 777 subjects purchased product. | |||||||||||||||||||||||||||||||||||||||
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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 |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Patterns of Use Cohort | |||||||||||||||||||||||||||||||||||||||
Arm description |
A subject was included in the Patterns of Use User Population if he/she completed the enrollment interview, purchased the investigational product, was randomized into the Patterns of Use Cohort, and provided e-diary data regarding their use. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Naproxen Sodium Extended Release (ER) Tablet
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Investigational medicinal product code |
BAYH6689
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Other name |
Aleve 24 Hour
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
660 milligram Naproxen Sodium extended release tablet orally administered.
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Arm title
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Reasons for Misuse Cohort | |||||||||||||||||||||||||||||||||||||||
Arm description |
A subject was included in the Reasons for Misuse Interviewed Population if he/she completed the enrollment interview, purchased the investigational product, was randomized into the Reasons for Misuse Cohort, misused on one or more occasions (did not comply with the label directions [took more than one tablet per dose or a subsequent dose less than 22 hours later]), and completed the reasons for misuse questions. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Naproxen Sodium Extended Release Tablet
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Investigational medicinal product code |
BAYH6689
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Other name |
Aleve 24 Hour
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
660 milligram Naproxen Sodium extended release tablet orally administered.
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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: Only interviewed subjects were assessed for the baseline assessment and hence, number of subjects for baseline assessment were less than number of subjects completed the study period. |
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Baseline characteristics reporting groups
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Reporting group title |
Patterns of Use Cohort
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Reporting group description |
A subject was included in the Patterns of Use User Population if he/she completed the enrollment interview, purchased the investigational product, was randomized into the Patterns of Use Cohort, and provided e-diary data regarding their use. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Reasons for Misuse Cohort
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Reporting group description |
A subject was included in the Reasons for Misuse Interviewed Population if he/she completed the enrollment interview, purchased the investigational product, was randomized into the Reasons for Misuse Cohort, misused on one or more occasions (did not comply with the label directions [took more than one tablet per dose or a subsequent dose less than 22 hours later]), and completed the reasons for misuse questions. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Patterns of Use Cohort
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Reporting group description |
A subject was included in the Patterns of Use User Population if he/she completed the enrollment interview, purchased the investigational product, was randomized into the Patterns of Use Cohort, and provided e-diary data regarding their use. | ||
Reporting group title |
Reasons for Misuse Cohort
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Reporting group description |
A subject was included in the Reasons for Misuse Interviewed Population if he/she completed the enrollment interview, purchased the investigational product, was randomized into the Reasons for Misuse Cohort, misused on one or more occasions (did not comply with the label directions [took more than one tablet per dose or a subsequent dose less than 22 hours later]), and completed the reasons for misuse questions. | ||
Subject analysis set title |
Naproxen Sodium ER (BAYH6689)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects were allowed to purchase a maximum of two bottles of Naproxen Sodium ER during their participation in the trial. The package instructed subjects to take one tablet every 24 hours while symptoms lasted for no more than 10 consecutive days for pain and no more than three consecutive days for fever.
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End point title |
Estimated Percentage of Misuse for Non-Therapeutic Reasons [1] | ||||||||
End point description |
The primary objective of this trial was to determine the percentage of non-therapeutic misuse. Two aspects of consumer use of Aleve 24 Hour were examined: the frequency at which consumers exceeded the label-defined daily dose modified by those who did so for non-therapeutic reasons.
Subjects in Patterns of Use cohort who took the product and subjects in Reason for Misuse cohort who completed interview were included in this analysis.
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End point type |
Primary
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End point timeframe |
28 days
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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 |
Non-therapeutic Reasons for Misuse | ||||||||
End point description |
Those subjects in the Reasons for Misuse Cohort who did not state misuse due to need for additional pain relief were categorized to Non-therapeutic misuse. Subjects in Reason for Misuse cohort who misused the product due to non-therapeutic reasons were included in this analysis.
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End point type |
Secondary
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End point timeframe |
28 days
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| No statistical analyses for this end point | |||||||||
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End point title |
Estimated Percentage of Misuse for Non-Therapeutic Reasons Using the First 10-Day Treatment Course | ||||||||
End point description |
This endpoint was an assessment of whether the rate of non-therapeutic misuse exceeded the pre-defined acceptable threshold for non-therapeutic misuse. The difference lay in the estimation of misuse in the Patterns of Use Cohort by using 10-day treatment courses rather than by “use day”. A treatment course for each subject began on the first day they recorded taking one or more tablets which was followed by nine consecutive “evaluable days.”
Subjects in Patterns of Use cohort who took the product and Reasons for misuse interviewed population were included in this analysis.
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End point type |
Secondary
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End point timeframe |
28 days
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects Took >/= 2 Tablets/Use Day in Any 10 Use Days | ||||||||
End point description |
Percentage of subjects took greater than or equal to (>/=) 2 tablets/use day in any 10 use days thus exceeding the label directions during a treatment course. Subjects in Patterns of Use User Population who had at least 10 use days of the product were included in this analysis.
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End point type |
Secondary
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End point timeframe |
28 days
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects Who Took Product With Mean Daily Use >/= 2 Tablets /Use Day | ||||||||
End point description |
Percentage of subjects who took product with mean daily use >/= 2 tablets /use day thus exceeding the label directions on any use day. Subjects in Patterns of Use User Population who had at least 10 use days of the product were included in this analysis.
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End point type |
Secondary
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End point timeframe |
28 days
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With at Least One Dosing Occasion Where More Than One Tablet Was Taken | ||||||||
End point description |
Percentage of subjects with at least one dosing occasion where more than one tablet was taken thus exceeding the label directions. Subjects in Patterns of Use cohort who took the product were included in the analysis.
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End point type |
Secondary
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End point timeframe |
28 days
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Dosing Occasions Where More Than One Tablet Was Taken | ||||||||
End point description |
Percentage of dosing occasions where more than one tablet was taken thus exceeding the label directions. Subjects in Patterns of Use cohort who took the product were included in this analysis.
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End point type |
Secondary
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End point timeframe |
28 days
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| Notes [2] - Number of Dosing occasions Analyzed = 9895. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects Where a Dose Was Taken Less Than 22 Hours After the Most Recent Previous Dose | ||||||||
End point description |
Percentage of subjects where a dose was taken less than 22 hours after the most recent previous dose thus exceeding the label directions. 22 hours was chosen to allow for some imprecision in subjects' recollection. Subjects in Patterns of Use cohort who took the product were included in this analysis.
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End point type |
Secondary
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End point timeframe |
28 days
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Dosing Occasions Where a Dose Was Taken Less Than 22 Hours After the Most Recent Previous Dose | ||||||||
End point description |
Percentage of dosing occasions where a dose was taken less than 22 hours after the most recent previous dose. 22 hours was chosen to allow for some imprecision in subjects' recollection. Subjects in Patterns of Use cohort who took the product were included in this analysis.
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End point type |
Secondary
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End point timeframe |
28 days
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| Notes [3] - Number of Dosing occasions Analyzed = 9895. |
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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 |
28 days
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Adverse event reporting additional description |
Adverse events were collected at the Follow-up telephone interview after completion of the 28 day Use Phase or sooner if they discontinued from the study. The safety population consisted of all subjects who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.
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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 |
Subjects were allowed to purchase a maximum of two bottles of Naproxen Sodium ER during their participation in the trial. The package instructed subjects to take one tablet every 24 hours while symptoms lasted for no more than 10 consecutive days for pain and no more than three consecutive days for fever. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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21 Sep 2011 |
The amendment included below changes -
- Added upper age limit for assent for subjects in Alabama
- Added Rapid Estimate of Adult Literacy in Medicine (REALM) Teen Test
- Added condition for closing enrollment for non-heavy users
- Added follow-up for unresolved Adverse events at completion or early discontinuation of study
- Changed when subjects were sent a reminder via the e-diary from “only if thy missed entry for that day” to “regardless of entering data for that day”
- Specified that adverse event severity and relationship to investigational product would be assigned by the principal investigator at PEGUS physician. |
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03 Nov 2011 |
This amendment included below changes -
- Added telephone contact with subjects who had missing e-diary days after 28 days to ask about product use on days subject did not make e-diary entries, if applicable
- Clarified that enrollment would be closed after approximately 500 subjects had been enrolled into the Patterns of Use Cohort.
- Added end-of-study e-diary review and process for subject to review and add information to e-diary prior to returning it
- Adjusted sample size from 400 to 500 based on estimated percentage of subjects who would provide detailed use information. |
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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. | |||
| Decimal places were automatically truncated if last decimal equals zero. | |||
