Trial Outcomes & Findings for Actual Use Trial of Naproxen Sodium (NCT NCT01427803)

NCT ID: NCT01427803

Last Updated: 2015-10-15

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 778 participants
• Primary outcome timeframe: 28 days
• Results posted on: 2015-10-15

Participant Flow

Participant milestones

Measure	Patterns of Use Cohort 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.	Reasons for Misuse Cohort 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.
Overall Study STARTED	526	252
Overall Study Purchased Product	525	252
Overall Study Baseline Assessment	516	130
Overall Study Took Product	508	237
Overall Study COMPLETED	463	226
Overall Study NOT COMPLETED	63	26

Reasons for withdrawal

Measure	Patterns of Use Cohort 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.	Reasons for Misuse Cohort 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.
Overall Study Lost to Follow-up	32	26
Overall Study Withdrawal by Subject	20	0
Overall Study Unable to complete full treatment period	6	0
Overall Study Protocol Violation	1	0
Overall Study Physician Decision	3	0
Overall Study did not take product	1	0

Baseline Characteristics

Actual Use Trial of Naproxen Sodium

Baseline characteristics by cohort

Measure	Patterns of Use User Population n=516 Participants 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.	Reasons for Misuse Interviewed Population n=130 Participants 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.	Total n=646 Participants Total of all reporting groups
Age, Customized 12 to 17 Years	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Age, Customized 18 to 24 Years	25 Participants n=5 Participants	4 Participants n=7 Participants	29 Participants n=5 Participants
Age, Customized 25 to 34 Years	63 Participants n=5 Participants	13 Participants n=7 Participants	76 Participants n=5 Participants
Age, Customized 35 to 44 Years	81 Participants n=5 Participants	28 Participants n=7 Participants	109 Participants n=5 Participants
Age, Customized 45 to 54 Years	142 Participants n=5 Participants	30 Participants n=7 Participants	172 Participants n=5 Participants
Age, Customized 55 Years or Older	202 Participants n=5 Participants	55 Participants n=7 Participants	257 Participants n=5 Participants
Sex: Female, Male Female	295 Participants n=5 Participants	68 Participants n=7 Participants	363 Participants n=5 Participants
Sex: Female, Male Male	221 Participants n=5 Participants	62 Participants n=7 Participants	283 Participants n=5 Participants

PRIMARY outcome

Timeframe: 28 days

Population: Participants in Patterns of Use cohort who took the product + Participants in Reason for Misuse cohort who completed interview

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.

Outcome measures

Measure	Naproxen Sodium ER (BAYH6689) n=632 Participants 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.
Estimated Percentage of Misuse for Non-Therapeutic Reasons	6.5 Percentage of Participants

SECONDARY outcome

Timeframe: 28 days

Population: Participants in Reason for Misuse cohort who misused the product due to non-therapeutic reasons were included in this analysis

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.

Outcome measures

Measure	Naproxen Sodium ER (BAYH6689) n=130 Participants 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.
Non-therapeutic Reasons for Misuse	52 Participants

SECONDARY outcome

Timeframe: 28 days

Population: Participants in Patterns of Use cohort who took the product + Reasons for misuse interviewed population

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."

Outcome measures

Measure	Naproxen Sodium ER (BAYH6689) n=632 Participants 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.
Estimated Percentage of Misuse for Non-Therapeutic Reasons Using the First 10-Day Treatment Course	5 Percentage of participants

SECONDARY outcome

Timeframe: 28 days

Population: Participants in Patterns of Use User Population who had at least 10 use days of the product

Percentage of participants took >/= 2 tablets/use day in any 10 use days thus exceeding the label directions during a treatment course.

Outcome measures

Measure	Naproxen Sodium ER (BAYH6689) n=375 Participants 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.
Percentage of Participants Took >/= 2 Tablets/Use Day in Any 10 Use Days	14.9 Percentage of participants

SECONDARY outcome

Timeframe: 28 days

Population: Participants in Patterns of Use User Population who had at least 10 use days of the product

Percentage of participants who took product with mean daily use >/= 2 tablets /use day thus exceeding the label directions on any use day.

Outcome measures

Measure	Naproxen Sodium ER (BAYH6689) n=375 Participants 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.
Percentage of Participants Who Took Product With Mean Daily Use >/= 2 Tablets /Use Day	4.8 Percentage of participants

SECONDARY outcome

Timeframe: 28 days

Population: Participants in Patterns of Use cohort who took the product

Percentage of participants with at least one dosing occasion where more than one tablet was taken thus exceeding the label directions.

Outcome measures

Measure	Naproxen Sodium ER (BAYH6689) n=502 Participants 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.
Percentage of Participants With at Least One Dosing Occasion Where More Than One Tablet Was Taken	19.7 Percentage of participants

SECONDARY outcome

Timeframe: 28 days

Population: Participants in Patterns of Use cohort who took the product

Percentage of dosing occasions where more than one tablet was taken thus exceeding the label directions.

Outcome measures

Measure	Naproxen Sodium ER (BAYH6689) n=9895 Dosing occasions 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.
Percentage of Dosing Occasions Where More Than One Tablet Was Taken	5.4 Percentage of dosing occasions

SECONDARY outcome

Timeframe: 28 days

Population: Participants in Patterns of Use cohort who took the product

Percentage of participants where a dose was taken less than 22 hours after the most recent previous dose thus exceeding the label directions. 22 hrs was chosen to allow for some imprecision in subjects' recollection.

Outcome measures

Measure	Naproxen Sodium ER (BAYH6689) n=502 Participants 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.
Percentage of Participants Where a Dose Was Taken Less Than 22 Hours After the Most Recent Previous Dose	72.5 Percentage of participants

SECONDARY outcome

Timeframe: 28 days

Population: Participants in Patterns of Use cohort who took the product

Percentage of dosing occasions where a dose was taken less than 22 hours after the most recent previous dose. 22 hrs was chosen to allow for some imprecision in subjects' recollection

Outcome measures

Measure	Naproxen Sodium ER (BAYH6689) n=9895 Dosing occasions 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.
Percentage of Dosing Occasions Where a Dose Was Taken Less Than 22 Hours After the Most Recent Previous Dose	27.8 Percentage of dosing occasions

Adverse Events

Naproxen Sodium ER (BAYH6689)

Serious events: 6 serious events

Other events: 89 other events

Deaths: 0 deaths

Serious adverse events

Measure	Naproxen Sodium ER (BAYH6689) n=745 participants at risk 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.
Injury, poisoning and procedural complications overdose	0.13% 1/745 • Number of events 1 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.
Cardiac disorders cardiac failure congestive	0.13% 1/745 • Number of events 1 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.
Gastrointestinal disorders diarrhea haemorrhagic	0.13% 1/745 • Number of events 1 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.
Infections and infestations viral infection	0.13% 1/745 • Number of events 1 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.
Hepatobiliary disorders gallbladder disorder	0.13% 1/745 • Number of events 1 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.
Immune system disorders hypersensitivity	0.13% 1/745 • Number of events 1 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.

Other adverse events

Measure	Naproxen Sodium ER (BAYH6689) n=745 participants at risk 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.
Gastrointestinal disorders abdominal pain upper	1.9% 14/745 • Number of events 15 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.
Gastrointestinal disorders constipation	1.6% 12/745 • Number of events 12 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.
Gastrointestinal disorders diarrhoea	1.5% 11/745 • Number of events 11 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.
Infections and infestations nasopharyngitis	2.7% 20/745 • Number of events 20 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.
Nervous system disorders headache	1.9% 14/745 • Number of events 15 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.
Infections and infestations sinusitis	1.3% 10/745 • Number of events 10 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.
Musculoskeletal and connective tissue disorders back pain	1.1% 8/745 • Number of events 8 • 28 days AEs 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 participants who took product. Safety data from the two cohorts were pooled in one group as both cohorts received the same treatment.

Additional Information

Head Medical Affairs

Bayer HealthCare LLC, Consumer Care

Email: clinical-trials-contact@bayerhealthcare.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60