Acetaminophen/Naproxen Sodium Dose Ranging Study

Phase 2

Completed

Conditions: Pain

Interventions: Drug: Acetaminophen/naproxen sodium Dose A
Drug: Acetaminophen/naproxen sodium Dose D
Drug: Placebo
Drug: Acetaminophen/naproxen sodium Dose B
Drug: Acetaminophen/naproxen sodium Dose C
Drug: Acetaminophen/naproxen sodium Dose E

Registration Number: NCT04447040

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

Brief Summary: Study assessing the relative efficacy of five strengths of a fixed combination of acetaminophen and naproxen sodium is being investigated to help inform selection of dose(s) for further development and to evaluate the safety of a fixed combination of naproxen sodium and acetaminophen.

Detailed Description: This is a randomized, double-blind, placebo-controlled study to evaluate the analgesic efficacy and safety profile of the following doses of a fixed combination of Acetaminophen (APAP)/Naproxen sodium (NPX) administered as a single two-tablet dose:\[Acetaminophen/Naproxen Sodium Dose A, Acetaminophen/Naproxen Sodium Dose B, Acetaminophen/Naproxen Sodium Dose C, Acetaminophen/Naproxen Sodium Dose D, Acetaminophen/Naproxen Sodium Dose E and Placebo\] following surgical extraction of four third molars.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 304

Inclusion Criteria

Males or females 17-50 years old
Weigh 100 pounds or greater and have a body mass index (BMI) of 17.5-35.4 (inclusive) at screening
Surgical removal of three or 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 a known allergy or hypersensitivity to naproxen or other NSAIDs, including aspirin, or to acetaminophen, oxycodone or other opioids;
Not able to swallow whole 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, or substance abuse, as judged by the investigator site staff, in the last 5 years
Use of any immunosuppressive drugs within 2 weeks of screening
History of endoscopically documented peptic ulcer disease or bleeding disorder in the last 2 years

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acetaminophen/naproxen sodium Dose A	Acetaminophen/naproxen sodium Dose A	Acetaminophen/naproxen sodium Dose A administered as a single two-tablet dose.
Acetaminophen/naproxen sodium Dose D	Acetaminophen/naproxen sodium Dose D	Acetaminophen/naproxen sodium Dose D administered as a single two-tablet dose.
Placebo	Placebo	Placebo tablets administered as a single two-tablet dose.
Acetaminophen/naproxen sodium Dose B	Acetaminophen/naproxen sodium Dose B	Acetaminophen/naproxen sodium Dose B administered as a single two-tablet dose.
Acetaminophen/naproxen sodium Dose C	Acetaminophen/naproxen sodium Dose C	Acetaminophen/naproxen sodium Dose C administered as a single two-tablet dose.
Acetaminophen/naproxen sodium Dose E	Acetaminophen/naproxen sodium Dose E	Acetaminophen/naproxen sodium Dose E administered as a single two-tablet dose.

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 on Day 1	Time weighted sum of the pain intensity difference (SPID) score is derived from pain intensity difference (PID) score. Pain intensity-numerical rating scale (PI-NRS) was used to assess pain intensity on scale ranged from 0 (no pain) to 10 (very severe pain), higher score indicated severe pain intensity. PID score was the difference between baseline pain intensity and pain intensity at assessment timepoint (12 hours). The SPID 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 interval from 0 to 12 hours. The possible range of SPID for 0 to 12 hours was from -120 to 120. A higher value of SPID indicated greater pain relief.

Secondary Outcome Measures

Name	Time	Method
Time Weighted Sum of Pain Intensity Difference Score From 6 Hours to 12 Hours (SPID 6-12)	From 6 hours up to 12 hours post-dose on Day 1	Time weighted sum of the pain intensity difference (SPID) score is derived from PID score. PI-NRS was used to assess pain intensity on scale ranged from 0 (no pain) to 10 (very severe pain), higher score indicated severe pain intensity. PID was the difference between pain intensity at 6 hours and pain intensity at assessment timepoint (12 hours). The SPID 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 6 to 12 hours (6 hours). The possible range of SPID for 6 to12 hours was from -60 to 60. A higher value of SPID indicated greater pain relief.
Time to First Use of Rescue Analgesic Medication	From 0 minute up to 1440 minutes post-dose (that is, up to 24 hours post-dose) on Day 1	Time to first use of rescue analgesic medication was measured as the elapsed time (in minutes) from when the investigational product was given until the time rescue analgesic was first given. Participants who did not use rescue medication during the 24 hour study period had their time to rescue set to 24 hours and were censored at 24 hours. Kaplan-Meier method was used for the analysis.
Proportion of Participants Who Required Rescue Analgesic Medication	From 0 hour up to 24 hours post-dose on Day 1	Proportion (cumulative data) of participants who used rescue analgesic medication through 24 hours post study drug administration on Day 1 which was assessed by using Kaplan-Meier estimates were reported.
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 on Day 1	Time weighted total pain relief (TOTPAR) was measured using a Pain Relief Numerical Rating Scale (PR-NRS) ranging from 0 to10 (0 = no relief, 10 = complete relief). A higher score indicated greater pain relief. Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each post-dose 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 were indicative of more pain relief.