Postoperative Dental Pain
Conditions
Keywords
Postoperative Dental Pain
Brief summary
The purpose of this study is to compare the pain relieving effect of different doses of MK0663 with placebo and other pain relievers/analgesics in patients with postoperative dental pain. Pain intensity and relief will be measured by the total pain relief score (TOPAR) and patient evaluation.
Interventions
etoricoxib 90 mg; 120 mg (once daily) over three days.
DRUGComparator: ibuprofen
ibuprofen 2400 mg (600 mg Q6h) over three Days
DRUGComparator: acetaminophen + codeine
acetaminophen 2400 mg/codeine 240 mg (600/60 mg Q6h) over three Days
DRUGComparator: placebo
matching placebo over three Days
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be scheduled to have 2 or more third molars removed, at least 1 of which is partially embedded in bone and is impacted in the lower jaw * Patients must be experiencing moderate to severe pain following the dental procedure
Exclusion criteria
* Previous molar extraction within the past 45 days * Personal or family history of an inherited bleeding disorder * Uncontrolled high blood pressure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Pain Relief Score Over the First 6 Hours Post the Initial Day 1 Dose of the Study Medication (TOPAR6) | Over the first 6 hours post the initial Day 1 dose of the study medication | TOPAR6 was calculated by multiplying the pain relief (PR) score (0- to 4-point Likert scale, with 0=None, and 4=Complete for pain relief) at each time point by the duration (in hours) since the preceding time point, and summing these weighted values up to 6 hours post the initial Day 1 dose. The range of TOPAR6 score is 0 to 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | At 24 hours post the initial Day 1 dose of the study medication | Patient's Global Assessment of Study Medication was on 0- to 4- point scale, with 0=Poor, and 4=Excellent for patient's rating of the study medication for pain. |
Participant flow
Recruitment details
Study Conducted at 3 investigational sites in the US. Patients were recruited from the sites patient pool and through advertising. A total of 588 patients were randomized. First Patient Entered 27-June-2008; First Patient In (randomized) on 03-July- 2008; Last Patient Last Visit 08-Jan-09
Pre-assignment details
Patients who met entry criteria and were experiencing moderate-to-severe pain after removal of at least 2 third molars (at least 1 being partially or completely impacted and of mandibular origin) were allocated to the study. Wash-out period for exclusionary medication was specified in the protocol. Randomization was stratified by baseline pain.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo orally once daily | 46 |
| Etoricoxib 90 mg Etoricoxib 90 mg orally once daily | 191 |
| Etoricoxib 120 mg Etoricoxib 120 mg orally once daily | 97 |
| Ibuprofen 2400 mg Ibuprofen 2400 mg (600 mg every 6 hours (Q6h)) orally | 192 |
| Acetaminophen 2400 mg/Codeine 240 mg Acetaminophen 2400 mg/Codeine 240 mg (600/60 mg Q6h) orally | 62 |
| Total | 588 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 1 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Etoricoxib 90 mg | Etoricoxib 120 mg | Ibuprofen 2400 mg | Acetaminophen 2400 mg/Codeine 240 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 21.0 years STANDARD_DEVIATION 3 | 21.8 years STANDARD_DEVIATION 3.6 | 21.8 years STANDARD_DEVIATION 3.5 | 21.6 years STANDARD_DEVIATION 3.8 | 20.5 years STANDARD_DEVIATION 2.8 | 21.5 years STANDARD_DEVIATION 3.5 |
| Baseline Pain Intensity Moderate | 21 Participants | 98 Participants | 49 Participants | 106 Participants | 30 Participants | 304 Participants |
| Baseline Pain Intensity Severe | 25 Participants | 93 Participants | 48 Participants | 86 Participants | 32 Participants | 284 Participants |
| Body Weight | 71.21 Kilograms STANDARD_DEVIATION 16.33 | 72.53 Kilograms STANDARD_DEVIATION 16.68 | 71.02 Kilograms STANDARD_DEVIATION 15.96 | 72.24 Kilograms STANDARD_DEVIATION 16.81 | 69.43 Kilograms STANDARD_DEVIATION 13.99 | 71.76 Kilograms STANDARD_DEVIATION 16.29 |
| Duration of Surgery | 0.14 Hours STANDARD_DEVIATION 0.06 | 0.13 Hours STANDARD_DEVIATION 0.06 | 0.15 Hours STANDARD_DEVIATION 0.08 | 0.14 Hours STANDARD_DEVIATION 0.06 | 0.13 Hours STANDARD_DEVIATION 0.06 | 0.14 Hours STANDARD_DEVIATION 0.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 52 Participants | 25 Participants | 50 Participants | 17 Participants | 155 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 139 Participants | 72 Participants | 142 Participants | 44 Participants | 432 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Height | 171.03 Centimeters STANDARD_DEVIATION 8.91 | 168.39 Centimeters STANDARD_DEVIATION 9.95 | 167.92 Centimeters STANDARD_DEVIATION 10.07 | 168.50 Centimeters STANDARD_DEVIATION 9.05 | 168.38 Centimeters STANDARD_DEVIATION 9.86 | 168.56 Centimeters STANDARD_DEVIATION 9.59 |
| Mean Impaction Score | 2.41 Units on a Scale STANDARD_DEVIATION 0.51 | 2.44 Units on a Scale STANDARD_DEVIATION 0.5 | 2.40 Units on a Scale STANDARD_DEVIATION 0.52 | 2.50 Units on a Scale STANDARD_DEVIATION 0.48 | 2.40 Units on a Scale STANDARD_DEVIATION 0.51 | 2.45 Units on a Scale STANDARD_DEVIATION 0.5 |
| Number of Hours from End of Surgery to Dosing | 3.06 Hours STANDARD_DEVIATION 0.79 | 2.94 Hours STANDARD_DEVIATION 0.77 | 2.84 Hours STANDARD_DEVIATION 0.75 | 3.01 Hours STANDARD_DEVIATION 0.84 | 2.97 Hours STANDARD_DEVIATION 0.78 | 2.96 Hours STANDARD_DEVIATION 0.79 |
| Number of Teeth Removed | 2.04 Teeth STANDARD_DEVIATION 0.29 | 2.06 Teeth STANDARD_DEVIATION 0.27 | 2.10 Teeth STANDARD_DEVIATION 0.39 | 2.02 Teeth STANDARD_DEVIATION 0.12 | 2.03 Teeth STANDARD_DEVIATION 0.18 | 2.05 Teeth STANDARD_DEVIATION 0.26 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 6 Participants | 4 Participants | 9 Participants | 0 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 1 Participants | 7 Participants | 3 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 5 Participants | 3 Participants | 1 Participants | 1 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 43 Participants | 174 Participants | 86 Participants | 173 Participants | 56 Participants | 532 Participants |
| Sex: Female, Male Female | 25 Participants | 113 Participants | 50 Participants | 115 Participants | 37 Participants | 340 Participants |
| Sex: Female, Male Male | 21 Participants | 78 Participants | 47 Participants | 77 Participants | 25 Participants | 248 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 46 | 54 / 191 | 28 / 97 | 57 / 192 | 35 / 62 |
| serious Total, serious adverse events | 0 / 46 | 0 / 191 | 0 / 97 | 0 / 192 | 0 / 62 |
Outcome results
Primary
Total Pain Relief Score Over the First 6 Hours Post the Initial Day 1 Dose of the Study Medication (TOPAR6)
TOPAR6 was calculated by multiplying the pain relief (PR) score (0- to 4-point Likert scale, with 0=None, and 4=Complete for pain relief) at each time point by the duration (in hours) since the preceding time point, and summing these weighted values up to 6 hours post the initial Day 1 dose. The range of TOPAR6 score is 0 to 24.
Time frame: Over the first 6 hours post the initial Day 1 dose of the study medication
Population: Full Analysis Set population (all randomized patients who received at least 1 dose of study treatment and had at least 1 post-baseline PR data over the first 6 hours). Observed PR was used up to rescue. Missing data was imputed by linear interpolation at time points before rescue, by last-observation-carried-forward at time points after rescue.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Pain Relief Score Over the First 6 Hours Post the Initial Day 1 Dose of the Study Medication (TOPAR6) | 5.08 Units on a Scale | Standard Error 0.86 |
| Etoricoxib 90 mg | Total Pain Relief Score Over the First 6 Hours Post the Initial Day 1 Dose of the Study Medication (TOPAR6) | 16.10 Units on a Scale | Standard Error 0.42 |
| Etoricoxib 120 mg | Total Pain Relief Score Over the First 6 Hours Post the Initial Day 1 Dose of the Study Medication (TOPAR6) | 15.73 Units on a Scale | Standard Error 0.59 |
| Ibuprofen 2400 mg | Total Pain Relief Score Over the First 6 Hours Post the Initial Day 1 Dose of the Study Medication (TOPAR6) | 15.67 Units on a Scale | Standard Error 0.42 |
| Acetaminophen 2400 mg/Codeine 240 mg | Total Pain Relief Score Over the First 6 Hours Post the Initial Day 1 Dose of the Study Medication (TOPAR6) | 11.83 Units on a Scale | Standard Error 0.74 |
p-value: <0.001ANOVA
p-value: <0.001ANOVA
95% CI: [-1.37, 1.48]
95% CI: [-0.73, 1.6]
95% CI: [2.04, 5.76]
95% CI: [2.61, 5.94]
95% CI: [-1.8, 1.05]
95% CI: [8.72, 12.47]
95% CI: [4.53, 8.97]
Secondary
Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication
Patient's Global Assessment of Study Medication was on 0- to 4- point scale, with 0=Poor, and 4=Excellent for patient's rating of the study medication for pain.
Time frame: At 24 hours post the initial Day 1 dose of the study medication
Population: Full Analysis Set population (all randomized patients who received at least 1 dose of study treatment and had at least 1 post-baseline assessment at 24 hours). Observed data was used. Forty patients were excluded from the analysis due to no measurement at 24 hours after the initial Day 1 dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Excellent | 3 Participants |
| Placebo | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Fair | 12 Participants |
| Placebo | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Very Good | 5 Participants |
| Placebo | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Good | 5 Participants |
| Placebo | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Poor | 19 Participants |
| Etoricoxib 90 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Fair | 12 Participants |
| Etoricoxib 90 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Very Good | 66 Participants |
| Etoricoxib 90 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Poor | 12 Participants |
| Etoricoxib 90 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Excellent | 51 Participants |
| Etoricoxib 90 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Good | 43 Participants |
| Etoricoxib 120 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Good | 20 Participants |
| Etoricoxib 120 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Very Good | 26 Participants |
| Etoricoxib 120 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Excellent | 28 Participants |
| Etoricoxib 120 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Fair | 5 Participants |
| Etoricoxib 120 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Poor | 7 Participants |
| Ibuprofen 2400 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Excellent | 35 Participants |
| Ibuprofen 2400 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Poor | 6 Participants |
| Ibuprofen 2400 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Fair | 24 Participants |
| Ibuprofen 2400 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Good | 42 Participants |
| Ibuprofen 2400 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Very Good | 73 Participants |
| Acetaminophen 2400 mg/Codeine 240 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Very Good | 18 Participants |
| Acetaminophen 2400 mg/Codeine 240 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Good | 15 Participants |
| Acetaminophen 2400 mg/Codeine 240 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Fair | 13 Participants |
| Acetaminophen 2400 mg/Codeine 240 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Poor | 1 Participants |
| Acetaminophen 2400 mg/Codeine 240 mg | Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication | Excellent | 7 Participants |
p-value: <0.001stratified Wilcoxon rank sum test
p-value: <0.001stratified Wilcoxon rank sum test
p-value: 0.161stratified Wilcoxon rank sum test
p-value: 0.014stratified Wilcoxon rank sum test
p-value: 0.007stratified Wilcoxon rank sum test