Trial Outcomes & Findings for Study to Collect Information on How Well the Study Drug Naproxen Sodium Tablets Works Compared to Hydrocodone/Acetaminophen Tablets in Order to Relieve Pain in Participants Experiencing Moderate to Severe Pain After Having Their Wisdom Teeth Removed (NCT NCT04307940)
NCT ID: NCT04307940
Last Updated: 2022-07-14
Results Overview
Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. Sum of Pain Intensity Differences (SPIDs) was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 12 hours ranges from -120 to 120. A higher value indicates a better pain reduction.
COMPLETED
PHASE4
221 participants
Up to 12 hours postdose
2022-07-14
Participant Flow
Study was conducted at one center in the US between 12-MAR-2020 (first participant first visit) and 05-OCT-2020 (last participant last visit).
Overall, 221 participants were randomized into this post-operative dental pain study; 90 participants received naproxen sodium treatment, 87 participants received hydrocodone/APAP (acetaminophen) treatment, and 44 participants received placebo.
Participant milestones
| Measure |
Naproxen Sodium
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone / APAP
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
|---|---|---|---|
|
Overall Study
STARTED
|
90
|
87
|
44
|
|
Overall Study
COMPLETED
|
85
|
84
|
42
|
|
Overall Study
NOT COMPLETED
|
5
|
3
|
2
|
Reasons for withdrawal
| Measure |
Naproxen Sodium
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone / APAP
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
3
|
1
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
1
|
Baseline Characteristics
Study to Collect Information on How Well the Study Drug Naproxen Sodium Tablets Works Compared to Hydrocodone/Acetaminophen Tablets in Order to Relieve Pain in Participants Experiencing Moderate to Severe Pain After Having Their Wisdom Teeth Removed
Baseline characteristics by cohort
| Measure |
Naproxen Sodium
n=90 Participants
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone / APAP
n=87 Participants
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
n=44 Participants
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
Total
n=221 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
19.3 Years
STANDARD_DEVIATION 1.62 • n=5 Participants
|
19.3 Years
STANDARD_DEVIATION 1.69 • n=7 Participants
|
19.3 Years
STANDARD_DEVIATION 2.00 • n=5 Participants
|
19.3 Years
STANDARD_DEVIATION 1.72 • n=4 Participants
|
|
Sex: Female, Male
Female
|
50 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
112 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
40 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
109 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
18 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
42 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
72 Participants
n=5 Participants
|
69 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
179 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Baseline pain intensity
Moderate
|
34 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
87 Participants
n=4 Participants
|
|
Baseline pain intensity
Severe
|
56 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
134 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to 12 hours postdosePopulation: PP Population: all subjects in safety population who provided at least one pain assessment after the first dose of study drug and did not have any major protocol violations and completed the 12-hour assessments.
Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. Sum of Pain Intensity Differences (SPIDs) was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 12 hours ranges from -120 to 120. A higher value indicates a better pain reduction.
Outcome measures
| Measure |
Naproxen Sodium
n=86 Participants
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone / APAP
n=83 Participants
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
n=43 Participants
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
|---|---|---|---|
|
Sum of Pain Intensity Difference Over 12 Hours (SPID 0-12)
|
53.20 Scores on a scale*hours
Standard Error 3.09
|
38.39 Scores on a scale*hours
Standard Error 3.14
|
13.57 Scores on a scale*hours
Standard Error 4.35
|
SECONDARY outcome
Timeframe: Up to 12 hours postdosePopulation: PP Population: all subjects in safety population who provided at least one pain assessment after the first dose of study drug and did not have any major protocol violations and completed the 12-hour assessments.
Pain relief is measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = A little relief, 2 = Some relief, 3 = A lot of relief, 4 = Complete relief). Total Pain Relief is calculated as the area under the curve of pain relief score over time for the given time period by multiplying the pain relief score at each time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. TOTPAR over 12 hours ranges from 0 to 48, a higher value indicates more pain relief.
Outcome measures
| Measure |
Naproxen Sodium
n=86 Participants
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone / APAP
n=83 Participants
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
n=43 Participants
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
|---|---|---|---|
|
Total Pain Relief Over 12 Hours (TOTPAR 0-12)
|
28.41 Scores on a scale*hours
Standard Error 1.36
|
21.31 Scores on a scale*hours
Standard Error 1.39
|
10.63 Scores on a scale*hours
Standard Error 1.92
|
SECONDARY outcome
Timeframe: Up to 6 hours postdosePopulation: PP Population: all subjects in safety population who provided at least one pain assessment after the first dose of study drug and did not have any major protocol violations and completed the 12-hour assessments.
Pain relief is measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = A little relief, 2 = Some relief, 3 = A lot of relief, 4 = Complete relief). Total Pain Relief is calculated as the area under the curve of pain relief score over time for the given time period by multiplying the pain relief score at each time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. TOTPAR over 6 hours ranges from 0 to 24, a higher value indicates more pain relief.
Outcome measures
| Measure |
Naproxen Sodium
n=86 Participants
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone / APAP
n=83 Participants
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
n=43 Participants
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
|---|---|---|---|
|
Total Pain Relief Over 6 Hours (TOTPAR 0-6)
|
14.53 Scores on a scale*hours
Standard Error 0.61
|
12.69 Scores on a scale*hours
Standard Error 0.62
|
5.14 Scores on a scale*hours
Standard Error 0.87
|
SECONDARY outcome
Timeframe: Up to 6 hours postdosePopulation: PP Population: all subjects in safety population who provided at least one pain assessment after the first dose of study drug and did not have any major protocol violations and completed the 12-hour assessments.
Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. Sum of Pain Intensity Differences (SPIDs) was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 6 hours ranges from -60 to 60. A higher value indicates a better pain reduction.
Outcome measures
| Measure |
Naproxen Sodium
n=86 Participants
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone / APAP
n=83 Participants
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
n=43 Participants
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
|---|---|---|---|
|
Sum of Pain Intensity Difference Over 6 Hours (SPID 0-6)
|
28.41 Scores on a scale*hours
Standard Error 1.46
|
24.35 Scores on a scale*hours
Standard Error 1.48
|
6.23 Scores on a scale*hours
Standard Error 2.05
|
SECONDARY outcome
Timeframe: Up to 12 hours postdosePopulation: PP Population: all subjects in safety population who provided at least one pain assessment after the first dose of study drug and did not have any major protocol violations and completed the 12-hour assessments.
Outcome measures
| Measure |
Naproxen Sodium
n=86 Participants
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone / APAP
n=83 Participants
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
n=43 Participants
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
|---|---|---|---|
|
Number of Participants Required or Did Not Reqiure Rescue Pain Medication
Number of participants required rescue pain medication
|
18 Participants
|
43 Participants
|
29 Participants
|
|
Number of Participants Required or Did Not Reqiure Rescue Pain Medication
Number of participants did not require any rescue pain medication
|
68 Participants
|
40 Participants
|
14 Participants
|
SECONDARY outcome
Timeframe: Up to 12 hours postdosePopulation: PP Population: all subjects in safety population who provided at least one pain assessment after the first dose of study drug and did not have any major protocol violations and completed the 12-hour assessments.
To quantify the use of opioid analgesics in treatment of post-operative dental pain, the amount of rescue medications (opioids) was converted to a standard unit, which was Morphine Milligram Equivalent (MME) using below formula: MME/Day = Strength per Unit × (Number of units / Days supply) × MME conversion factor
Outcome measures
| Measure |
Naproxen Sodium
n=18 Participants
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone / APAP
n=43 Participants
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
n=29 Participants
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
|---|---|---|---|
|
Amount of Rescue Medication
|
7.8 Morphine Milligram Equivalent (MME)
Standard Deviation 3.08
|
9.3 Morphine Milligram Equivalent (MME)
Standard Deviation 4.02
|
10.5 Morphine Milligram Equivalent (MME)
Standard Deviation 4.50
|
SECONDARY outcome
Timeframe: Up to 12 hours postdosePopulation: PP Population: all subjects in safety population who provided at least one pain assessment after the first dose of study drug and did not have any major protocol violations and completed the 12-hour assessments.
If a subject did not take the rescue medication during the treatment period, (s)he was censored at the time of last assessment.
Outcome measures
| Measure |
Naproxen Sodium
n=86 Participants
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone / APAP
n=83 Participants
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
n=43 Participants
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
|---|---|---|---|
|
Time to First Use of Rescue Medication
|
NA Hours
NA = not estimable due to insufficient number of participants with events.
|
10.42 Hours
Interval 8.27 to
NA = not estimable due to insufficient number of participants with events.
|
2.57 Hours
Interval 1.83 to 7.6
|
SECONDARY outcome
Timeframe: Up to 12 hours postdosePopulation: PP Population: all subjects in safety population who provided at least one pain assessment after the first dose of study drug and did not have any major protocol violations and completed the 12-hour assessments.
Outcome measures
| Measure |
Naproxen Sodium
n=86 Participants
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone / APAP
n=83 Participants
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
n=43 Participants
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
|---|---|---|---|
|
Duration of Pain at Least Half Gone Over 12 Hours
|
8.87 Hours
Standard Error 0.46
|
6.57 Hours
Standard Error 0.46
|
3.31 Hours
Standard Error 0.64
|
SECONDARY outcome
Timeframe: Up to 6 hours postdosePopulation: PP Population: all subjects in safety population who provided at least one pain assessment after the first dose of study drug and did not have any major protocol violations and completed the 12-hour assessments.
Outcome measures
| Measure |
Naproxen Sodium
n=86 Participants
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone / APAP
n=83 Participants
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
n=43 Participants
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
|---|---|---|---|
|
Duration of Pain at Least Half Gone Over 6 Hours
|
4.60 Hours
Standard Error 0.22
|
4.08 Hours
Standard Error 0.22
|
1.49 Hours
Standard Error 0.31
|
Adverse Events
Naproxen Sodium
Hydrocodone/APAP
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Naproxen Sodium
n=90 participants at risk
Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions
|
Hydrocodone/APAP
n=87 participants at risk
Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions
|
Placebo
n=44 participants at risk
Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
|
|---|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
1.1%
1/90 • Number of events 1 • From first dose of the study drug administration until end of study treatment, up to 1 day
|
34.5%
30/87 • Number of events 53 • From first dose of the study drug administration until end of study treatment, up to 1 day
|
20.5%
9/44 • Number of events 16 • From first dose of the study drug administration until end of study treatment, up to 1 day
|
|
General disorders
General disorders and administration site conditions
|
0.00%
0/90 • From first dose of the study drug administration until end of study treatment, up to 1 day
|
1.1%
1/87 • Number of events 1 • From first dose of the study drug administration until end of study treatment, up to 1 day
|
0.00%
0/44 • From first dose of the study drug administration until end of study treatment, up to 1 day
|
|
Nervous system disorders
Nervous system disorders
|
1.1%
1/90 • Number of events 1 • From first dose of the study drug administration until end of study treatment, up to 1 day
|
10.3%
9/87 • Number of events 9 • From first dose of the study drug administration until end of study treatment, up to 1 day
|
9.1%
4/44 • Number of events 4 • From first dose of the study drug administration until end of study treatment, up to 1 day
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place