Dental Pain
Conditions
Keywords
Acetaminophen, Paracetamol Analgesics, Analgesics, Non-Narcotic Pain, Postoperative Pain, Antipyretics Dental Surgery, Third molar extraction
Brief summary
The purpose of the study is to evaluate the efficacy and safety of acetaminophen ER 1500 mg (two 750 mg tablets) over 10 to 12 hours in the dental pain model following third molar extraction(s) and to evaluate the pharmacokinetics of acetaminophen ER 1500 mg (two 750 mg tablets) in a sub-group of subjects.
Interventions
DRUGAcetaminophen ER
Single dose (2 tablets) Acetaminophen ER 750 mg
DRUGPlacebo
Single dose (2 tablets) Acetaminophen ER 750 mg matching placebo
Sponsors
McNeil Consumer Healthcare Division of McNEIL-PPC, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
17 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Must be at least 17 and less than 46 years of age * Must weigh at least 100 lbs with a body mass index of at least 18 and less than 30 * Scheduled to undergo surgical extraction of one impacted third molar from the lower jaw. The third molar from the upper jaw from the same side may also be removed. * Experiencing moderate to severe pain after extraction of third molars.
Exclusion criteria
* Cannot be allergic to acetaminophen (Tylenol) or any non-steroidal anti-inflammatory drugs (e.g., Motrin, Advil, Aleve, Naproxen). * Cannot be pregnant (or planning to be pregnant) or nursing a baby * Unable to swallow whole large tablets or caplets. * Cannot have any other medical conditions that the investigator feels may compromise your safety or the study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Weighted Sum of Pain Intensity Difference (PID) Over 10 Hours (SPID 0-10) | 10 Hours | Time weighted sum of pain intensity difference scores from baseline over 10 hours. Pain intensity was evaluated using a 0-10 numerical rating scale (NRS) where 0 = no pain and 10 = very severe pain. SPID 0-10 = 0.25 x (PID at 15 min + PID at 30 min + PID at 45 min + PID at 60 min + PID at 75 min + PID at 90 min) + 0.5 x (PID at 120 min) + PID at 3 h + PID at 4 h + PID at 5 h + PID at 6 h + PID at 7 h + PID at 8 h + PID at 9 h + PID at 10 h. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Confirmed First Perceptible Pain Relief | Within 12 Hours | Minutes until confirmed first perceptible pain relief was achieved. Stopwatch was started after the subject took the study medication. The subject was instructed to stop the stopwatch when they first began to feel any pain relief. The first perceptible pain relief was confirmed if the subject also stopped the second stopwatch indicating meaningful pain relief. |
| Time to Meaningful Pain Relief | Within 12 Hours | Minutes until meaningful pain relief was achieved. Stopwatch was started after the subject took the study medication. The subjects were instructed to stop the stopwatch when the relief from the starting pain was meaningful to them. |
| Duration of Pain Relief | Within 12 Hours | Minutes until rescue medication was given. |
| Patient Global Evaluation | 12 Hours | Patient Assessment of the pain medication - Number of subjects rating the medication they received as a pain reliever on a score of 0-4, where 0=poor, 1=fair, 2=good, 3=very good, 4=excellent. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (two matching placebo tablets) | 134 |
| ACE ER 1500 mg Acetaminophen ER 1500 mg (two 750 mg ER tablets) | 269 |
| Total | 403 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Could not swallow study medication | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | ACE ER 1500 mg | Total |
|---|---|---|---|
| Age, Continuous | 19.6 years STANDARD_DEVIATION 2.66 | 19.5 years STANDARD_DEVIATION 2.82 | 19.6 years STANDARD_DEVIATION 2.77 |
| Region of Enrollment USA | 134 participants | 269 participants | 403 participants |
| Sex: Female, Male Female | 72 Participants | 143 Participants | 215 Participants |
| Sex: Female, Male Male | 62 Participants | 126 Participants | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 134 | 26 / 268 |
| serious Total, serious adverse events | 0 / 134 | 0 / 268 |
Outcome results
Primary
Time Weighted Sum of Pain Intensity Difference (PID) Over 10 Hours (SPID 0-10)
Time weighted sum of pain intensity difference scores from baseline over 10 hours. Pain intensity was evaluated using a 0-10 numerical rating scale (NRS) where 0 = no pain and 10 = very severe pain. SPID 0-10 = 0.25 x (PID at 15 min + PID at 30 min + PID at 45 min + PID at 60 min + PID at 75 min + PID at 90 min) + 0.5 x (PID at 120 min) + PID at 3 h + PID at 4 h + PID at 5 h + PID at 6 h + PID at 7 h + PID at 8 h + PID at 9 h + PID at 10 h.
Time frame: 10 Hours
Population: Analysis was based on the Intent-to-Treat (ITT) population, which included all subjects who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time Weighted Sum of Pain Intensity Difference (PID) Over 10 Hours (SPID 0-10) | 5.745 units on a scale | Standard Error 2.5056 |
| ACE ER 1500 mg | Time Weighted Sum of Pain Intensity Difference (PID) Over 10 Hours (SPID 0-10) | 30.986 units on a scale | Standard Error 1.8951 |
Comparison: The null hypothesis was no difference between groups. The alternative hypothesis was a difference between groups.p-value: <0.00195% CI: [19.669, 30.813]ANOVA
Secondary
Duration of Pain Relief
Minutes until rescue medication was given.
Time frame: Within 12 Hours
Population: Analysis was based on the Intent-to-Treat (ITT) population, which included all subjects who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration of Pain Relief | 106.5 Minutes |
| ACE ER 1500 mg | Duration of Pain Relief | NA Minutes |
Comparison: The null hypothesis was no difference between groups. The alternative hypothesis was a difference between groups. Subjects who withdrew from the study before 12 hours, but did not use rescue therapy, were censored at the time of withdrawal. Subjects not rescuing during the 12-hour study period had their time to rescue set to 12 hours and were censored.p-value: <0.001Log Rank
Secondary
Patient Global Evaluation
Patient Assessment of the pain medication - Number of subjects rating the medication they received as a pain reliever on a score of 0-4, where 0=poor, 1=fair, 2=good, 3=very good, 4=excellent.
Time frame: 12 Hours
Population: Analysis was based on the Intent-to-Treat (ITT) population, which included all subjects who were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Patient Global Evaluation | Fair (1) | 9.0 percentage of participants |
| Placebo | Patient Global Evaluation | Very Good (3) | 12.8 percentage of participants |
| Placebo | Patient Global Evaluation | Good (2) | 8.3 percentage of participants |
| Placebo | Patient Global Evaluation | Excellent (4) | 6.8 percentage of participants |
| Placebo | Patient Global Evaluation | Poor (0) | 63.2 percentage of participants |
| ACE ER 1500 mg | Patient Global Evaluation | Excellent (4) | 20.1 percentage of participants |
| ACE ER 1500 mg | Patient Global Evaluation | Poor (0) | 18.3 percentage of participants |
| ACE ER 1500 mg | Patient Global Evaluation | Fair (1) | 11.2 percentage of participants |
| ACE ER 1500 mg | Patient Global Evaluation | Good (2) | 14.6 percentage of participants |
| ACE ER 1500 mg | Patient Global Evaluation | Very Good (3) | 35.8 percentage of participants |
Comparison: The null hypothesis was no difference between groups. The alternative hypothesis was a difference between groups.p-value: 0.001Cochran-Mantel-Haenszel
Secondary
Time to Confirmed First Perceptible Pain Relief
Minutes until confirmed first perceptible pain relief was achieved. Stopwatch was started after the subject took the study medication. The subject was instructed to stop the stopwatch when they first began to feel any pain relief. The first perceptible pain relief was confirmed if the subject also stopped the second stopwatch indicating meaningful pain relief.
Time frame: Within 12 Hours
Population: Analysis was based on the Intent-to-Treat (ITT) population, which included all subjects who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Confirmed First Perceptible Pain Relief | NA Minutes |
| ACE ER 1500 mg | Time to Confirmed First Perceptible Pain Relief | 26.817 Minutes |
Comparison: The null hypothesis was no difference between groups. The alternative hypothesis was a difference between groups.p-value: <0.001Wilcoxon test, from SAS PROC LIFETEST
Secondary
Time to Meaningful Pain Relief
Minutes until meaningful pain relief was achieved. Stopwatch was started after the subject took the study medication. The subjects were instructed to stop the stopwatch when the relief from the starting pain was meaningful to them.
Time frame: Within 12 Hours
Population: Analysis was based on the Intent-to-Treat (ITT) population, which included all subjects who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Meaningful Pain Relief | NA Minutes |
| ACE ER 1500 mg | Time to Meaningful Pain Relief | 84.675 Minutes |
Comparison: The null hypothesis was no difference between groups. The alternative hypothesis was a difference between groups.p-value: <0.001Wilcoxon test, from SAS PROC LIFETEST