Naproxen Sodium/Acetaminophen Proof of Concept Dosing Study

Phase 2

Completed

Conditions: Pain

Interventions: Drug: 10 mg hydrocodone + 650 mg acetaminophen
Drug: 440 mg naproxen sodium
Drug: 220 mg naproxen sodium with 650 mg acetaminophen
Drug: 440 mg naproxen sodium with 1000 mg acetaminophen
Drug: Placebo tablet

Registration Number: NCT03879408

Lead Sponsor: Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division

Brief Summary: Study assessing efficacy and safety of concomitantly dosed naproxen sodium with acetaminophen, compared with naproxen sodium, hydrocodone/acetaminophen and Placebo in a postoperative dental pain.

Detailed Description: This is a randomized, double-blind, placebo- and active-controlled, parallel-group study to evaluate the analgesic efficacy and safety of concomitantly administered naproxen sodium 440 mg with acetaminophen 1000 mg and concomitantly administered naproxen sodium 220 mg with acetaminophen 650 mg, compared with a fixed combination of hydrocodone 10 mg/acetaminophen 650 mg, naproxen sodium 440 mg, and placebo over a twelve-hour period after surgical extraction of four third molars.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 290

Inclusion Criteria

Males of females 17-50 years old
Weigh 100 pounds or greater and have a body mass index (BMI) of 18.5 to 35 (inclusive) at screening
Surgical removal of up to four third molars, of which, two must be mandibular impactions
Meets requirements for post -surgical pain level
Females of childbearing potential and males agree to contraceptive requirements of study
Have a negative urine drug screen at screening, and on day of surgical procedure

Exclusion Criteria

Pregnant female, breastfeeding, trying to become pregnant or male with pregnant partner or partner currently trying to become pregnant
Have known allergy or hypersensitivity to naproxen or other NSAIDS, including aspirin, or to acetaminophen, tramadol, hydrocodone or other opioids
Not able to swallow large tablets or capsules
History of any condition (s) in investigator's opinion, may jeopardize subject safety, well-being and integrity of study
Use analgesics 5 or more times per week
History of chronic tranquilizer use, heavy drinking, substance abuse as judged by investigator site staff within last 5 years
Use of immunosuppressive drugs within 2 weeks of screening
History of peptic ulcer disease or gastrointestinal bleeding in the last two years or hematologic bleeding

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
10 mg hydrocodone + 650 mg acetaminophen	10 mg hydrocodone + 650 mg acetaminophen	10 mg hydrocodone + 650 mg acetaminophen administered as a single dose of two hydrocodone 5 mg + acetaminophen 325 mg tablets and two placebo tablets
440 mg naproxen sodium	440 mg naproxen sodium	440 mg naproxen sodium administered as a single dose of two naproxen sodium 220 mg tablets and two placebo tablets
220 mg naproxen sodium with 650 mg acetaminophen	220 mg naproxen sodium with 650 mg acetaminophen	220 mg naproxen sodium with 650 mg acetaminophen administered as a single dose of one naproxen sodium 220 mg tablet and two acetaminophen 325 mg tablets and one placebo tablet
440 mg naproxen sodium with 1000 mg acetaminophen	440 mg naproxen sodium with 1000 mg acetaminophen	440 mg naproxen sodium with 1000 mg acetaminophen administered as a single dose of two naproxen sodium 220 mg tablets and two acetaminophen 500 mg tablets
Placebo tablet	Placebo tablet	Single dose of four placebo tablets

Primary Outcome Measures

Name	Time	Method
Time-weighted Sum of Pain Intensity Difference Score From Baseline (0 Hour) to 12 Hours (SPID 0-12)	Baseline (0 hour) up to 12 hours post-dose	Time-weighted sum of the pain intensity difference score was measured using a PI-NRS ranging from 0-10 (0 = no pain, 10 = very severe pain). The possible range of SPID for 0-12 hours was from -120 to 120. A higher value of SPID indicated greater pain relief. PID was the difference between baseline pain intensity and pain intensity at assessment (12 hours). Time-weighted sum of the pain intensity difference scores were derived by first multiplying each PID score by the time from the previous time point and adding these time-weighted PID scores together over the intervals from 0 to 12 hours.
Time-Weighted Sum of Pain Intensity Difference Score From Baseline (0 Hour) to 6 Hours (SPID 0-6)	Baseline (0 hour) up to 6 hours post-dose	Time-weighted sum of the pain intensity difference (SPID) score was measured using a Pain Intensity-Numerical Rating Scale (PI-NRS) ranging from 0-10 (0 = no pain, 10 = very severe pain). The possible range of SPID for 0-6 hours was from -60 to 60. A higher value of SPID indicated greater pain relief. PID was the difference between baseline pain intensity and pain intensity at assessment. Time-weighted sum of the pain intensity difference scores were derived by first multiplying each PID score by the time from the previous time point and adding these time-weighted PID scores together over the intervals from 0 to 6 hours.

Secondary Outcome Measures

Name	Time	Method
Time-Weighted Sum of Pain Intensity Difference Score From Baseline (0 Hour) to 8 Hours (SPID 0-8)	Baseline (0 hour) up to 8 hours post-dose	Time-weighted sum of the pain intensity difference score was measured using a PI-NRS ranging from 0-10 (0 = no pain, 10 = very severe pain). The possible range of SPID for 0-8 hours was from -80 to 80. A higher value of SPID indicated greater pain relief. PID was the difference between baseline pain intensity and pain intensity at assessment (8 hours). Time-weighted sum of the pain intensity difference scores were derived by first multiplying each PID score by the time from the previous time point and adding these time-weighted PID scores together over the intervals from 0 to 8 hours.
Pain Relief (PAR) Scores at Individual Timepoints	0.25 hours, 0.5 hours, 0.75 hours, 1 hours, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, and 12 hours	Participants answered a question at individual time points: "how much relief do you have from your starting pain?" on a 11-point PR-NRS. Scale ranged from 0=no relief to 10=complete relief. Higher score indicated improvement in pain.
Time-Weighted Sum of Total Pain Relief Score From Baseline (0 Hour) to 6 Hours (TOTPAR 0-6)	Baseline (0 hour) up to 6 hours post-dose	Time-weighted total pain relief (TOTPAR) was measured using a Pain Relief Numerical Rating Scale (PR-NRS) ranging from 0-10 (0 = no relief, 10 = complete relief). Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values. The minimum value was 0, and the maximum value was 60. Higher scores was indicative of more pain relief.
Pain Intensity Difference (PID) Scores at Individual Time Points	0.25 hours, 0.5 hours, 0.75 hours, 1 hours, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, and 12 hours	Pain Intensity was self-reported over 12 hours, using a pain rating of 0-10 on the PI-NRS, with score ranged from 0-10 (0= no pain; 10 = worst imaginable pain). Pain intensity differences were calculated with respect to baseline at each time point after study drug administration.
Time-Weighted Sum of Total Pain Relief Score From Baseline (0 Hour) to 8 Hours (TOTPAR 0-8)	Baseline (0 hour) up to 8 hours post-dose	TOTPAR was measured using a PR-NRS ranging from 0-10 (0 = no relief, 10 = complete relief). Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values. The minimum value was 0, and the maximum value was 80. Higher scores was indicative of more pain relief.
Time-Weighted Sum of Total Pain Relief Score From Baseline (0 Hour) to 12 Hours (TOTPAR 0-12)	Baseline (0 hour) up to 12 hours post-dose	TOTPAR was measured using a PR-NRS ranging from 0-10 (0 = no relief, 10 = complete relief). Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values. The minimum value was 0, and the maximum value was 120. Higher scores was indicative of more pain relief.
Participant's Global Evaluation of Study Medication OR Overall Impression of Study Medication According to Participant's Global Evaluation	Up to 12 hours	Participants were asked to rate their overall impression of the study medication using the following scale: poor (0), fair (1), good (2), very good (3), and excellent (4) where higher score represented better outcome.