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

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04307940
• Collaborator: (none)
• Enrollment: 221
• Location: 1
• Arms: 3
• Actual Duration (Months): 6.8
• Patients Per Site Per Month: 32.5

Study Details

Study Description

Brief Summary

With this study researchers want to collect information on how long the pain relief lasts after a fixed dose of naproxen sodium or hydrocodone/acetaminophen or placebo (contains no medication) over 12 hours in subjects experiencing moderate to severe pain after having their wisdom teeth removed. Naproxen Sodium (Aleve®) is a drug that is used for the temporary relief of minor aches and pains.

Hydrocodone/Acetaminophen is a combination drug used to relieve moderate to severe pain. It contains an opioid (narcotic) pain reliever (hydrocodone) and a non-opioid pain reliever (acetaminophen).

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: Naproxen Sodium (Aleve, BAY117031); Drug: Hydrocodone/Acetaminophen; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 221 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Trial to Compare the Analgesic Efficacy and Safety of Naproxen Sodium Tablets and Hydrocodone/Acetaminophen Tablets in Postsurgical Dental Pain
• Actual Study Start Date: Mar 12, 2020
• Actual Primary Completion Date: Oct 2, 2020
• Actual Study Completion Date: Oct 5, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Naproxen sodium After completion of the surgical teeth extractions, qualified participants will be randomized into one of three treatments with a 2:2:1 ratio. (Naproxen sodium=2, Hydrocodone/Acetaminophen=2, Placebo=1)	Drug: Naproxen Sodium (Aleve, BAY117031); 220 mg per tablet, two tablets (440 mg), intake a single dose orally.
Active Comparator: Hydrocodone/Acetaminophen After completion of the surgical teeth extractions, qualified participants will be randomized into one of three treatments with a 2:2:1 ratio. (Naproxen sodium=2, Hydrocodone/Acetaminophen=2, Placebo=1)	Drug: Hydrocodone/Acetaminophen; 5/325 mg per tablet, two tablets (10/650 mg), intake a single dose orally.
Placebo Comparator: Placebo After completion of the surgical teeth extractions, qualified participants will be randomized into one of three treatments with a 2:2:1 ratio. (Naproxen sodium=2, Hydrocodone/Acetaminophen=2, Placebo=1)	Drug: Placebo; two tablets, intake a single dose orally.

Outcome Measures

Primary Outcome Measures

1. Sum of Pain Intensity Difference Over 12 Hours (SPID 0-12) [Up to 12 hours postdose]

   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.

Secondary Outcome Measures

1. Total Pain Relief Over 12 Hours (TOTPAR 0-12) [Up to 12 hours postdose]

   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.

2. Total Pain Relief Over 6 Hours (TOTPAR 0-6) [Up to 6 hours postdose]

   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.

3. Sum of Pain Intensity Difference Over 6 Hours (SPID 0-6) [Up to 6 hours postdose]

   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.

4. Number of Participants Required or Did Not Reqiure Rescue Pain Medication [Up to 12 hours postdose]

5. Amount of Rescue Medication [Up to 12 hours postdose]

   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

6. Time to First Use of Rescue Medication [Up to 12 hours postdose]

   If a subject did not take the rescue medication during the treatment period, (s)he was censored at the time of last assessment.

7. Duration of Pain at Least Half Gone Over 12 Hours [Up to 12 hours postdose]

8. Duration of Pain at Least Half Gone Over 6 Hours [Up to 6 hours postdose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Healthy, ambulatory, male or female volunteers 18 to 40 years of age;

• Subjects will undergo surgical extraction of three or four third molars, two of which must be mandibular molars. Maxillary third molars may be removed regardless of impaction level. The mandibular extractions must have a trauma rating of mild or moderate and meet one of the following scenarios:

• two full bony impactions

• two partial bony impactions

• one full bony impaction in combination with one partial bony impaction Supernumerary teeth present may also be removed at the discretion of the oral surgeon;

• Have not consumed alcoholic beverages, or foods and beverages containing caffeine (examples; coffee, tea, chocolate, and colas) after midnight prior to surgery and agree not to consume any of these foods or beverages throughout their stay at the study site;

• Use of only short-acting local anesthetic (e.g., mepivacaine or lidocaine) preoperatively, with or without a vasoconstrictor and nitrous oxide at the discretion of the Investigator;

• Have moderate to severe postoperative pain on the Categorical Pain Intensity Scale (a score of at least 2 on a 4 point scale) and a score of ≥ 5 on the 0-10 pain intensity NRS within 4.5 hours postsurgery;

• Ability to understand and follow study-related instructions;

• Be willing and able to participate in all scheduled visits, treatment plan, and trial procedures according to the clinical protocol;

Exclusion Criteria:

• History of hypersensitivity to naproxen sodium, hydrocodone/acetaminophen, ibuprofen, NSAIDS, aspirin, similar pharmacological agents, local anesthetics, rescue medication or components of the investigational products;

• Evidence or history of clinically significant (in the judgment of the investigator) hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including hypertension), hepatic, psychiatric, neurologic diseases, or malignancies within the last 5 years;

• Subjects with the following medical conditions may be eligible at the discretion of the investigator: ADHD on a stable dose regimen of methylphenidate/(dextro)amphetamine for at least 6 months; subjects with hypothyroidism on a stable dose of synthetic thyroid hormone for at least 6 months;

• Have received any form of treatment in the form of medication for depression in the past 6 months or any form of psychotropic agent (including selective serotonin uptake inhibitors [SSRI] but excluding ADHD medications described above) within the last 6 months;

• Use of any OTC or prescription medications with which the administration of naproxen, hydrocodone/acetaminophen, acetaminophen, ibuprofen, any other NSAID, (e.g., tramadol) or if a medication is contraindicated;

• Females who are planning to become pregnant, pregnant or lactating;

• Habituation to analgesic drugs including opioids (i.e., routine use of oral analgesics 5 or more times per week for greater than 3 weeks within the past 2 years);

• Alcoholism or drug abuse within 2 years prior to the Screening Visit or routine consumption of 3 or more alcohol containing beverages per day; Alcohol containing beverages are defined as one beer (5%), one glass of wine (11%) and one shot (40%) hard liquor;

• Surgeon's trauma rating of severe following surgery;

• Unwilling or unable to comply with all requirements outlined in the protocol;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	JBR Clinical Research	Salt Lake City	Utah	United States	84107

Sponsors and Collaborators

• Bayer

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 19, 2019
• Statistical Analysis Plan - Jan 21, 2021

More Information

Additional Information:

• Click here to find results for studies related to Bayer products

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT04307940
• Other Study ID Numbers: 20536
• First Posted: Mar 13, 2020
• Last Update Posted: Jul 14, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Bayer: Postsurgical Dental Pain
• Additional relevant MeSH terms: Acetaminophen; Naproxen; Acetaminophen, hydrocodone drug combination; Hydrocodone

Study Results

Participant Flow

Recruitment Details	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).
Pre-assignment Detail	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.

Arm/Group Title	Naproxen Sodium	Hydrocodone / APAP	Placebo
Arm/Group Description	Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
Period Title: Overall Study
STARTED	90	87	44
COMPLETED	85	84	42
NOT COMPLETED	5	3	2

Baseline Characteristics

Arm/Group Title	Naproxen Sodium	Hydrocodone / APAP	Placebo	Total
Arm/Group Description	Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions	Total of all reporting groups
Overall Participants	90	87	44	221
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	19.3 (1.62)	19.3 (1.69)	19.3 (2.00)	19.3 (1.72)
Sex: Female, Male (Count of Participants)
Female	50 55.6%	42 48.3%	20 45.5%	112 50.7%
Male	40 44.4%	45 51.7%	24 54.5%	109 49.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	18 20%	18 20.7%	6 13.6%	42 19%
Not Hispanic or Latino	72 80%	69 79.3%	38 86.4%	179 81%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Baseline pain intensity (Count of Participants)
Moderate	34 37.8%	36 41.4%	17 38.6%	87 39.4%
Severe	56 62.2%	51 58.6%	27 61.4%	134 60.6%

Outcome Measures

1. Primary Outcome

Title	Sum of Pain Intensity Difference Over 12 Hours (SPID 0-12)
Description	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.
Time Frame	Up to 12 hours postdose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Naproxen Sodium	Hydrocodone / APAP	Placebo
Arm/Group Description	Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
Measure Participants	86	83	43
Least Squares Mean (Standard Error) [Scores on a scale*hours]	53.20 (3.09)	38.39 (3.14)	13.57 (4.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Naproxen Sodium, Hydrocodone / APAP
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	All p-values were presented using two-sided test with alpha 0.05 and were considered statistically significant.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	14.81
	Confidence Interval	(2-Sided) 95%; 6.10 to 23.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Naproxen Sodium, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	All p-values were presented using two-sided test with alpha 0.05 and were considered statistically significant.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	39.63
	Confidence Interval	(2-Sided) 95%; 29.08 to 50.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Hydrocodone / APAP, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	All p-values were presented using two-sided test with alpha 0.05 and were considered statistically significant.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	24.82
	Confidence Interval	(2-Sided) 95%; 14.26 to 35.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Total Pain Relief Over 12 Hours (TOTPAR 0-12)
Description	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.
Time Frame	Up to 12 hours postdose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Naproxen Sodium	Hydrocodone / APAP	Placebo
Arm/Group Description	Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
Measure Participants	86	83	43
Least Squares Mean (Standard Error) [Scores on a scale*hours]	28.41 (1.36)	21.31 (1.39)	10.63 (1.92)

3. Secondary Outcome

Title	Total Pain Relief Over 6 Hours (TOTPAR 0-6)
Description	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.
Time Frame	Up to 6 hours postdose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Naproxen Sodium	Hydrocodone / APAP	Placebo
Arm/Group Description	Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
Measure Participants	86	83	43
Least Squares Mean (Standard Error) [Scores on a scale*hours]	14.53 (0.61)	12.69 (0.62)	5.14 (0.87)

4. Secondary Outcome

Title	Sum of Pain Intensity Difference Over 6 Hours (SPID 0-6)
Description	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.
Time Frame	Up to 6 hours postdose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Naproxen Sodium	Hydrocodone / APAP	Placebo
Arm/Group Description	Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
Measure Participants	86	83	43
Least Squares Mean (Standard Error) [Scores on a scale*hours]	28.41 (1.46)	24.35 (1.48)	6.23 (2.05)

5. Secondary Outcome

Title	Number of Participants Required or Did Not Reqiure Rescue Pain Medication
Time Frame	Up to 12 hours postdose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Naproxen Sodium	Hydrocodone / APAP	Placebo
Arm/Group Description	Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
Measure Participants	86	83	43
Number of participants required rescue pain medication	18 20%	43 49.4%	29 65.9%
Number of participants did not require any rescue pain medication	68 75.6%	40 46%	14 31.8%

6. Secondary Outcome

Title	Amount of Rescue Medication
Description	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
Time Frame	Up to 12 hours postdose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Naproxen Sodium	Hydrocodone / APAP	Placebo
Arm/Group Description	Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
Measure Participants	18	43	29
Mean (Standard Deviation) [Morphine Milligram Equivalent (MME)]	7.8 (3.08)	9.3 (4.02)	10.5 (4.50)

7. Secondary Outcome

Title	Time to First Use of Rescue Medication
Description	If a subject did not take the rescue medication during the treatment period, (s)he was censored at the time of last assessment.
Time Frame	Up to 12 hours postdose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Naproxen Sodium	Hydrocodone / APAP	Placebo
Arm/Group Description	Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
Measure Participants	86	83	43
Median (95% Confidence Interval) [Hours]	NA	10.42	2.57

8. Secondary Outcome

Title	Duration of Pain at Least Half Gone Over 12 Hours
Time Frame	Up to 12 hours postdose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Naproxen Sodium	Hydrocodone / APAP	Placebo
Arm/Group Description	Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
Measure Participants	86	83	43
Least Squares Mean (Standard Error) [Hours]	8.87 (0.46)	6.57 (0.46)	3.31 (0.64)

9. Secondary Outcome

Title	Duration of Pain at Least Half Gone Over 6 Hours
Time Frame	Up to 6 hours postdose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Naproxen Sodium	Hydrocodone / APAP	Placebo
Arm/Group Description	Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions	Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
Measure Participants	86	83	43
Least Squares Mean (Standard Error) [Hours]	4.60 (0.22)	4.08 (0.22)	1.49 (0.31)

Adverse Events

Time Frame	From first dose of the study drug administration until end of study treatment, up to 1 day
Arm/Group Title	Naproxen Sodium		Hydrocodone/APAP		Placebo
Arm/Group Description	Participants received a single dose of naproxen sodium tablets 440 mg (220 mg × 2 tablets) after surgical teeth extractions		Participants received a single dose of hydrocodone/acetaminophen tablets 10/650 mg (5/325 mg × 2 tablets) after surgical teeth extractions		Participants received a single dose of matching placebo tablets (2 tablets) after surgical teeth extractions
All Cause Mortality
	Naproxen Sodium		Hydrocodone/APAP		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/90 (0%)		0/87 (0%)		0/44 (0%)
Serious Adverse Events
	Naproxen Sodium		Hydrocodone/APAP		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/90 (0%)		0/87 (0%)		0/44 (0%)
Other (Not Including Serious) Adverse Events
	Naproxen Sodium		Hydrocodone/APAP		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/90 (2.2%)		33/87 (37.9%)		11/44 (25%)
Gastrointestinal disorders
Gastrointestinal disorders	1/90 (1.1%)	1	30/87 (34.5%)	53	9/44 (20.5%)	16
General disorders
General disorders and administration site conditions	0/90 (0%)	0	1/87 (1.1%)	1	0/44 (0%)	0
Nervous system disorders
Nervous system disorders	1/90 (1.1%)	1	9/87 (10.3%)	9	4/44 (9.1%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.