Study of MK-0663/Etoricoxib in Postorthopedic Knee Replacement Surgery Pain (MK-0663-098)

The pain intensity difference was measured at rest over Days 1 through 3 in patients treated with etoricoxib (120 mg, 90 mg) compared to placebo for the treatment of pain following total knee replacement orthopedic surgery. Pain intensity difference at rest was measured on a numerical rating scale (NRS) from 0 - 10 points (0=no pain, to 10=pain as bad as you can imagine). Comparison to placebo was conducted in a step-down manner (the 90-mg dose was evaluated only if the null hypotheses for co-primary endpoints \[Pain Intensity Difference (PID) and Morphine\] 120-mg doses were rejected). The primary analyses for change from baseline in average pain intensity at rest over Days 1 to 3 was performed using the longitudinal data analysis (LDA) method with the terms for baseline pain intensity (moderate or severe), type of anesthesia (spinal or general), treatment, day, and the interaction of day by treatment.

Time frame: Baseline and Days 1-3

Population: All randomized participants, excluding those who didn't receive at least 1 dose of study treatment, lacked 1 post-randomization measurement, were randomized at a specific site, or received continuous infusion of morphine by patient control analgesia (PCA). Per protocol, the ibuprofen arm was not included in this outcome measure.

The average total dose of morphine was assessed when participant received etoricoxib 120 milligram(mg)/90 mg compared to placebo. Opioids taken were converted to mg morphine equivalents according to the following conventions: 1 mg morphine sulphate=1 mg morphine,1 mg morphine hydrochloride=1.17 mg morphine. A 5 mg oxycodone tablet=2.5 mg morphine,12.5 mg meperidine =1.67 mg morphine. Least-squares mean back-transformed; estimate obtained from longitudinal analysis of variance (ANOVA) model on log-transformed morphine dose with terms for baseline pain intensity(moderate or severe),type of anesthesia (spinal, general), treatment, day, and the interaction of day by treatment.

Time frame: Days 1-3

Population: All randomized participants, excluding those who didn't receive at least 1 dose of study treatment, lacked 1 post-randomization measurement, were randomized at a specific site, or received continuous infusion of morphine by PCA. Per protocol, the ibuprofen arm was not included in this outcome measure.

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study product, is also an AE.

Time frame: Up to 7 days

Population: The analysis population consisted of all randomized patients who received at least one dose of study treatment.

An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study product, is also an AE.

Time frame: Up to 21 days

Population: The analysis population consisted of all randomized patients who received at least one dose of study treatment.

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study product, is also an AE. Edema is swelling caused by excess fluid trapped in body tissues.

Time frame: Up to 21 days

Population: The analysis population consisted of all randomized patients who received at least one dose of study treatment.

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study product, is also an AE.

Time frame: Up to 21 days

Population: The analysis population consisted of all randomized patients who received at least one dose of study treatment.

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study product, is also an AE. Opioid-related AEs include nausea, vomiting, constipation, somnolence, respiratory depression, urinary retention and ileus.

Time frame: Up to 21 days

Population: The analysis population consisted of all randomized patients who received at least one dose of study treatment.

The pain intensity difference was measured at rest over Days 1 through 3 in participants treated with etoricoxib (120 mg, 90 mg) compared to ibuprofen for the treatment of pain following total knee replacement orthopedic surgery. Pain intensity difference at rest was measured on a numerical rating scale (NRS) from 0 - 10 points (0=no pain, to 10=pain as bad as you can imagine). Comparison to ibuprofen was conducted in a step-down manner (the 90-mg dose was evaluated only if the null hypotheses for co-primary endpoints \[Pain Intensity Difference (PID) and morphine\] 120-mg doses were rejected). The primary analyses for change from baseline in average pain intensity at rest over Days 1 to 3 was performed using the longitudinal data analysis (LDA) method with the terms for baseline pain intensity (moderate or severe), type of anesthesia (spinal or general), treatment, day, and the interaction of day by treatment.

Time frame: Baseline and Days 1-3

Population: All randomized participants, excluding those who didn't receive at least 1 dose of study treatment, lacked 1 post-randomization measurement, were randomized at a specific site, or received continuous infusion of morphine by patient control analgesia (PCA). Per protocol, the placebo arm was not included in this outcome measure.

The difference in average total daily dose of morphine used over Days 1 through 3 between participants treated with etoricoxib (120 mg, 90 mg) or ibuprofen 1800 mg (administered as 600 mg three times daily, every 8 hours) in the treatment of pain following total knee replacement orthopedic surgery was assessed. Opioids taken were converted to mg morphine equivalents according to the following conventions:1 mg morphine sulphate = 1 mg morphine, 1 mg morphine hydrochloride = 1.17 mg morphine. A 5 mg oxycodone tablet = 2.5 mg morphine,12.5 mg meperidine = 1.67 mg morphine.

Time frame: Days 1-3

Population: All randomized participants, excluding those who didn't receive at least 1 dose of study treatment, lacked 1 post-randomization measurement, were randomized at a specific site, or received continuous infusion of morphine by patient control analgesia (PCA). Per protocol, the placebo arm was not included in this outcome measure.