Study to Assess the Safety and Efficacy of Etoricoxib Versus Ibuprofen in the Treatment of Dysmenorrhea (MK-0663-145 AM1)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01462370
• Collaborator: (none)
• Enrollment: 139
• Arms: 2
• Duration (Months): 7

Study Details

Study Description

Brief Summary

This is a study to determine the overall analgesic effect of a single oral dose of etoricoxib compared to ibuprofen in participants with moderate-to-severe primary dysmenorrhea.

Condition or Disease	Intervention/Treatment	Phase
Dysmenorrhea	Drug: Etoricoxib; Drug: Ibuprofen; Drug: Placebo to etoricoxib; Drug: Placebo to ibuprofen; Drug: Acetaminophen 250 mg, isopropylantipyrine 150 mg and anhydrous caffeine 50 mg	Phase 3

Detailed Description

Participants who meet all the study entry criteria will be randomly allocated to 2 possible sequences of the 2 treatment regimens over the course of 2 menstrual cycles.

In treatment sequence 1, participants will receive etoricoxib 120 mg daily in menstrual cycle 1, and ibuprofen up to 2400 mg/daily in menstrual cycle 2. In treatment sequence 2, participants will receive ibuprofen up to 2400 mg/daily in menstrual cycle 1 and etoricoxib 120 mg daily in menstrual cycle 2.

Study Design

• Study Type: Interventional
• Actual Enrollment: 139 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized, Active-Comparator-Controlled, 2-period, Crossover, Double-Blind Study in China to Assess the Safety and Efficacy of Etoricoxib 120 mg Versus Ibuprofen up to 2400 mg (600 mg Q6h) in the Treatment of Patients With Primary Dysmenorrhea
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Etoricoxib+placebo ibuprofen then placebo etorcoxib+ibuprofen Participants will receive one tablet (active or placebo etoricoxib) and 3 capsules (active or placebo ibuprofen) as their first dose of study medication in Cycle 1 and Cycle 2. They can also take 3 capsules (active or placebo ibuprofen) up to 3 times more per day in Cycle 1 and Cycle 2.	Drug: Etoricoxib; Etoricoxib 120 mg tablet given orally for one dose.; Drug: Ibuprofen; Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.; Drug: Placebo to etoricoxib; Placebo to etoricoxib, one tablet.; Drug: Placebo to ibuprofen; Placebo to ibuprofen, up to four 3-capsule doses.; Drug: Acetaminophen 250 mg, isopropylantipyrine 150 mg and anhydrous caffeine 50 mg; Provided to participants as rescue medication. Participants may take 2 tablets at a time and up to 3 doses within 24 hours for rescue purposes.; Other Names: Saridon
Experimental: Ibuprofen+placebo etoricoxib then etoricoxib+placebo ibuprofen Participants will receive one tablet (active or placebo etoricoxib) and 3 capsules (active or placebo ibuprofen) as their first dose of study medication in Cycle 1 and Cycle 2. They can also take 3 capsules (active or placebo ibuprofen) up to 3 times more per day in Cycle 1 and Cycle 2.	Drug: Etoricoxib; Etoricoxib 120 mg tablet given orally for one dose.; Drug: Ibuprofen; Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.; Drug: Placebo to etoricoxib; Placebo to etoricoxib, one tablet.; Drug: Placebo to ibuprofen; Placebo to ibuprofen, up to four 3-capsule doses.; Drug: Acetaminophen 250 mg, isopropylantipyrine 150 mg and anhydrous caffeine 50 mg; Provided to participants as rescue medication. Participants may take 2 tablets at a time and up to 3 doses within 24 hours for rescue purposes.; Other Names: Saridon

Outcome Measures

Primary Outcome Measures

1. Total Pain Relief Score Over the First 6 Hours (TOPAR6) After the Initial Dose [Baseline and 0.5, 1, 1.5, 2, 3, 4, 5 and 6 hours]

   TOPAR6 was calculated by multiplying the pain relief (PR) score (0- to 4-point 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, with increasing scores indicating greater pain relief.

Secondary Outcome Measures

1. Sum of Pain Intensity Difference Scores Over the 6-Hour Time Period (SPID6) [Baseline and 0.5, 1, 1.5, 2, 3, 4, 5 and 6 hours]

   The Pain Intensity Difference (PID) score is the difference between the baseline pain intensity (PI) score and the PI score recorded at each time point post initial dose, as calculated by subtracting the pain intensity at each of the subsequent time points from the baseline pain intensity score; therefore, it is on a -1 to 3 scale, with a large value representing a greater treatment effect. SPID6 is derived by multiplying the PID score at each time point by the duration (in hours) since the preceding time point, and summing these weighted values up to 6 hours and it is on a scale of -6 to 18.

2. Mean Participant Global Evaluation of Pain at 6 Hours After the Initial Dose (GLOBAL6) [6 hours]

   The GLOBAL6 was recorded by the participant at 6 hours (or at the time of rescue medication use) after taking the first dose of study medication. The GLOBAL6 uses a pain relief scale of 0 to 4, where 0 = poor pain relief, 1 = fair pain relief, 2 = good pain relief, 3 = very good pain relief, and 4 = excellent pain relief.

3. Mean Participant Global Evaluation of Pain at 24 Hours After the Initial Dose (GLOBAL24) [24 hours]

   The GLOBAL24 was recorded by the participant at 24 hours (or at the time of rescue medication use) after taking the first dose of study medication. The GLOBAL24 uses a pain relief scale of 0 to 4, where 0 = poor pain relief, 1 = fair pain relief, 2 = good pain relief, 3 = very good pain relief, and 4 = excellent pain relief.

4. Mean Time to >=1 Unit Improvement From Baseline in Pain Intensity During the 6 Hours After the Initial Dose [Baseline and 6 hours]

   The time to a change from baseline in pain intensity score of >=1 unit on the pain intensity scale was calculated. The pain intensity scale rates participant pain on a scale of -1 to 3, with larger values associated with greater treatment effect.

5. Peak Pain Intensity Difference (PID) During the 6 Hours After the Initial Dose [Baseline and 0.5, 1, 1.5, 2, 3, 4, 5 and 6 hours]

   Peak PID during the 6 hours post initial dose is defined as the maximum PID score recorded during first 6 hours after the initial dose of study medication. PID is evaluated on a scale of -1 to 3, with larger values representing a greater treatment effect.

6. Peak Pain Relief (Peak PR) During the 6 Hours After the Initial Dose [Up to 6 hours]

   Peak PR during the 6 hours post initial dose is defined as the maximum PR score recorded during the first 6 hours after the initial dose of study medication. PR is recorded on a scale of 0 to 4, with 0 = no pain relief, 1 = little pain relief, 2 = some pain relief, 3 = a lot of pain relief, and 4 = complete pain relief.

7. Number of Participants Using Rescue Medication 24 Hours After the Initial Dose [24 Hours]

   Acetaminophen 250 mg, isopropylantipyrine 150 mg and anhydrous caffeine 50 mg (Saridon) was provided to each participant as rescue medication. Participants were permitted to take 2 tablets at a time and up to 3 doses within 24 hours of dosing of study drug for rescue purposes.

8. PID at Up to 12 Hours Following the Initial Dose [Baseline and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 and 12 hours]

   PID during the 12 hours following the initial dose is defined as the maximum PID score recorded during first 12 hours after the initial dose of study medication. PID is evaluated on a scale from 0 to 3, with 0 = no pain, 1 = slight pain, 2 = moderate pain, and 3 = severe pain.

9. PR at Up to 12 Hours Following the Initial Dose [Up to 12 hours]

   PR during the 12 hours following the initial dose is defined as the maximum PR score recorded during the first 12 hours after the initial dose of study medication. PR is evaluated on a scale of 0 to 4, with 0 = no pain relief, 1= a little pain relief, 2 = some pain relief, 3 = a lot of pain relief, and 4 = complete pain relief.

10. PID at Up to 24 Hours Following the Initial Dose [Baseline and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 20 and 24 hours]

    PID during the 24 hours following the initial dose is defined as the maximum PID score recorded during first 24 hours after the initial dose of study medication. PID is evaluated on a scale from 0 to 3, with 0 = no pain, 1 = slight pain, 2 = moderate pain, and 3 = severe pain.

11. PR at Up to 24 Hours Following the Initial Dose [Up to 24 hours]

    PR during the 24 hours following the initial dose is defined as the maximum PR score recorded during the first 24 hours after the initial dose of study medication. PR is evaluated on a scale of 0 to 4, with 0 = no pain relief, 1= a little pain relief, 2 = some pain relief, 3 = a lot of pain relief, and 4 = complete pain relief.

12. Number of Participants With a Global Evaluation of Study Medication of Good, Very Good, or Excellent at 6 Hours After the Initial Dose [6 hours]

    At 6 hours following the initial dose. participants were asked to rate their perception of pain control as poor, fair, good, very good, or excellent. The number of participants that reported good, very good, or excellent pain control at 6 hours post initial dose were summed.

13. Number of Participants With a Global Evaluation of Study Medication of Good, Very Good, or Excellent at 24 Hours After the Initial Dose [24 Hours]

    At 24 hours following the initial dose of study medication, participants were asked to rate their perception of pain control as poor, fair, good, very good, or excellent. The number of participants that reported good, very good, or excellent pain control at 24 hours post initial dose were summed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Agree to remain abstinent or use double-barrier contraception throughout the study. Participants who are status post tubal ligation are exempt from this requirement.

• Moderate or severe primary dysmenorrhea during a minimum of 4 of the previous 6 menstrual cycles. Moderate: Over-the-counter analgesics provide significant relief in most menstrual cycles; discomfort interferes with usual activity. Severe: Over-the-counter analgesics not consistently effective, or prescription analgesics required in at least some menstrual cycles; discomfort is incapacitating causing an inability to work or do usual activity.

• Willing to limit alcohol intake to 2 drinks or equivalent per day for the duration of the study and follow-up period as well as to avoid exercise during the first 24 hours postdose in each menstrual cycle.

• Able to read, understand, and complete diary.

Exclusion Criteria:

• Use of an intrauterine device. Pregnant, breast feeding, or <6 weeks postpartum.

• Active gastric ulcer or history of inflammatory bowel disease.

• Uncontrolled hypertension.

• Uncontrolled diabetes mellitus or renal disease.

• Class II-IV congestive heart failure.

• Coronary artery bypass graft surgery, angioplasty, myocardial infarction, cerebrovascular accident or transient ischemic attack within the past 6 months.

• Unstable angina.

• Mild, moderate, or severe hepatic insufficiency.

• Any personal or family history of an inherited or acquired bleeding disorder.

• History of neoplastic disease; Exceptions: 1)adequately treated basal cell carcinoma or carcinoma in situ of the cervix; 2) other malignancies which have been successfully treated > or equal to 5 years prior to screening. Participants with a history of leukemia, lymphoma, malignant melanoma, and myeloproliferative disease are ineligible for the study regardless of the time since treatment.

• Allergic to etoricoxib, ibuprofen, acetaminophen, indomethacin, or other nonsteroidal anti-inflammatory drugs (NSAIDs), or cyclooxygenase (COX)-2 inhibitors, or to components in Saridon (propyphenazone/paracetamol/caffeine).

• Recent history of chronic analgesic or tranquilizer use or dependence.

• Morbidly obese and demonstrates significant health problems stemming from the obesity.

• Current user of recreational or illicit drugs or had a recent history of drug or alcohol abuse or dependence.

• Participated in another clinical study within the last 4 weeks.

• Not able to swallow oral medications: surgical or anatomical conditions that will preclude from swallowing and absorbing oral medications on an ongoing basis.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT01462370
• Other Study ID Numbers: 0663-145
• First Posted: Oct 31, 2011
• Last Update Posted: Feb 9, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Dysmenorrhea; Acetaminophen; Ibuprofen; Etoricoxib; Caffeine

Study Results

Participant Flow

Arm/Group Title	Etoricoxib 120 mg/ Ibuprofen Up to 2400 mg	Ibuprofen Up to 2400 mg / Etoricoxib 120 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally or one dose in menstrual cycle 1. In menstrual cycle 2, ibuprofen was administered at a dose of 600 mg every 4 hours as needed up to 2400 mg/day.	Ibuprofen 600 mg given orally up to for times a day as needed for a maximum of 2400 mg/day in menstrual cyle 1. In menstrual cycle 2, etoricoxib 120 mg ws given orally for one dose.
Period Title: Overall Study
STARTED	69	70
COMPLETED	68	65
NOT COMPLETED	1	5

Baseline Characteristics

Arm/Group Title	All Randomized Participants
Arm/Group Description	All participants randomized into the study.
Overall Participants	139
Age, Customized (Number) [Number]
<=20 years	14 10.1%
21-29 years	118 84.9%
>=30 years	7 5%
Sex: Female, Male (Count of Participants)
Female	139 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Total Pain Relief Score Over the First 6 Hours (TOPAR6) After the Initial Dose
Description	TOPAR6 was calculated by multiplying the pain relief (PR) score (0- to 4-point 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, with increasing scores indicating greater pain relief.
Time Frame	Baseline and 0.5, 1, 1.5, 2, 3, 4, 5 and 6 hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment and had at least one TOPAR6 observation up to 6 hours post initial dose of study medication.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	130	130
Least Squares Mean (Standard Error) [Score on a Scale]	17.38 (0.37)	16.49 (0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments	With at least 128 participants, the study had a 92% power to establish that etoricoxib is noninferior to ibuprofen (null hypothesis). The power and sample size were based on the following assumptions: 1) an approximately 15% protocol violation rate, 2) a noninferiority margin of -3.7 units (etoricoxib minus ibuprofen), and 3) an intrapatient standard deviation of 8 units.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The noninferiority margin is -3.7 units.
Statistical Test of Hypothesis	p-Value	0.043
	Comments	A priori threshold for statistical significance = <0.025 (one-sided).
	Method	ANOVA
	Comments	Adjusted for treatment, period, sequence, patient (sequence), and baseline pain intensity (moderate or severe).
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.03 to 1.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Sum of Pain Intensity Difference Scores Over the 6-Hour Time Period (SPID6)
Description	The Pain Intensity Difference (PID) score is the difference between the baseline pain intensity (PI) score and the PI score recorded at each time point post initial dose, as calculated by subtracting the pain intensity at each of the subsequent time points from the baseline pain intensity score; therefore, it is on a -1 to 3 scale, with a large value representing a greater treatment effect. SPID6 is derived by multiplying the PID score at each time point by the duration (in hours) since the preceding time point, and summing these weighted values up to 6 hours and it is on a scale of -6 to 18.
Time Frame	Baseline and 0.5, 1, 1.5, 2, 3, 4, 5 and 6 hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment, had at least one SPID6 observation up to 6 hours post initial dose of study medication, and had a baseline measurement.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	130	130
Least Squares Mean (Standard Error) [Score on a Scale]	9.48 (0.58)	9.27 (0.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.768
	Comments	A nominal threshold for statistical significance = <0.05.
	Method	ANOVA
	Comments	Adjusted for treatment, period, sequence, patient (sequence), and baseline pain intensity (moderate or severe).
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95%; -1.16 to 1.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Participant Global Evaluation of Pain at 6 Hours After the Initial Dose (GLOBAL6)
Description	The GLOBAL6 was recorded by the participant at 6 hours (or at the time of rescue medication use) after taking the first dose of study medication. The GLOBAL6 uses a pain relief scale of 0 to 4, where 0 = poor pain relief, 1 = fair pain relief, 2 = good pain relief, 3 = very good pain relief, and 4 = excellent pain relief.
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment and had a GLOBAL6 observation at 6 hours post initial dose of study medication.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	129	129
Least Squares Mean (Standard Error) [Score on a Scale]	2.50 (0.08)	2.24 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments	A nominal threshold for statistical significance = <0.05.
	Method	ANOVA
	Comments	Adjusted for treatment, period, sequence, patient (sequence), and baseline pain intensity (moderate or severe).
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.26
	Confidence Interval	(2-Sided) 95%; 0.07 to 0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Mean Participant Global Evaluation of Pain at 24 Hours After the Initial Dose (GLOBAL24)
Description	The GLOBAL24 was recorded by the participant at 24 hours (or at the time of rescue medication use) after taking the first dose of study medication. The GLOBAL24 uses a pain relief scale of 0 to 4, where 0 = poor pain relief, 1 = fair pain relief, 2 = good pain relief, 3 = very good pain relief, and 4 = excellent pain relief.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment had a GLOBAL24 observation at 24 hours post initial dose of study medication.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	129	129
Least Squares Mean (Standard Error) [Score on a Scale]	2.65 (0.08)	2.29 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	A nominal threshold for statistical significance = <0.05.
	Method	ANOVA
	Comments	Adjusted for treatment, period, sequence, patient (sequence), and baseline pain intensity (moderate or severe).
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.36
	Confidence Interval	(2-Sided) 95%; 0.17 to 0.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Mean Time to >=1 Unit Improvement From Baseline in Pain Intensity During the 6 Hours After the Initial Dose
Description	The time to a change from baseline in pain intensity score of >=1 unit on the pain intensity scale was calculated. The pain intensity scale rates participant pain on a scale of -1 to 3, with larger values associated with greater treatment effect.
Time Frame	Baseline and 6 hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment, had an observation at 6 hours post initial dose of study medication, and had a baseline measurement.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	130	130
Mean (95% Confidence Interval) [Hours]	1.0	1.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.371
	Comments	A priori threshold for statistical significance = <0.05.
	Method	Regression, Cox
	Comments	Adjusted for treatment, period, and baseline pain intensity.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Peak Pain Intensity Difference (PID) During the 6 Hours After the Initial Dose
Description	Peak PID during the 6 hours post initial dose is defined as the maximum PID score recorded during first 6 hours after the initial dose of study medication. PID is evaluated on a scale of -1 to 3, with larger values representing a greater treatment effect.
Time Frame	Baseline and 0.5, 1, 1.5, 2, 3, 4, 5 and 6 hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment and had a PID observation at up to 6 hours post initial dose of study medication.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	130	130
Least Squares Mean (Standard Error) [Score on a Scale]	2.2 (0.4)	2.1 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments	A priori threshold for statistical significance = <0.05.
	Method	ANOVA
	Comments	Adjusted for treatment, period, sequence, patient (sequence), and baseline pain intensity (moderate or severe).
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.00 to 0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Peak Pain Relief (Peak PR) During the 6 Hours After the Initial Dose
Description	Peak PR during the 6 hours post initial dose is defined as the maximum PR score recorded during the first 6 hours after the initial dose of study medication. PR is recorded on a scale of 0 to 4, with 0 = no pain relief, 1 = little pain relief, 2 = some pain relief, 3 = a lot of pain relief, and 4 = complete pain relief.
Time Frame	Up to 6 hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment and had at least one Peak PR observation up to 6 hours post initial dose of study medication.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	130	130
Least Squares Mean (Standard Error) [Score on a Scale]	3.70 (0.06)	3.52 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments	A priori threshold for statistical significance = <0.05.
	Method	ANOVA
	Comments	Adjusted for treatment, period, sequence, patient (sequence), and baseline pain intensity (moderate or severe).
Method of Estimation	Estimation Parameter	Mean Difference in LS Means
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; 0.03 to 0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Number of Participants Using Rescue Medication 24 Hours After the Initial Dose
Description	Acetaminophen 250 mg, isopropylantipyrine 150 mg and anhydrous caffeine 50 mg (Saridon) was provided to each participant as rescue medication. Participants were permitted to take 2 tablets at a time and up to 3 doses within 24 hours of dosing of study drug for rescue purposes.
Time Frame	24 Hours

Outcome Measure Data

Analysis Population Description

Due to the low number of participants requiring rescue medication use, the time to rescue medication use was not calculated.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	130	130
Number [Participants]	1 0.7%	4 NaN

9. Secondary Outcome

Title	PID at Up to 12 Hours Following the Initial Dose
Description	PID during the 12 hours following the initial dose is defined as the maximum PID score recorded during first 12 hours after the initial dose of study medication. PID is evaluated on a scale from 0 to 3, with 0 = no pain, 1 = slight pain, 2 = moderate pain, and 3 = severe pain.
Time Frame	Baseline and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 and 12 hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment and had at least one PID observation at up to 12 hours post initial dose of study medication.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	130	129
Least Squares Mean (Standard Error) [Score on a Scale]	2.28 (0.04)	2.07 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	A priori threshold for statistical significance = <0.05.
	Method	ANOVA
	Comments	Adjusted for treatment, period, sequence, patient (sequence), and baseline pain intensity (moderate or severe).
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; 0.10 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	PR at Up to 12 Hours Following the Initial Dose
Description	PR during the 12 hours following the initial dose is defined as the maximum PR score recorded during the first 12 hours after the initial dose of study medication. PR is evaluated on a scale of 0 to 4, with 0 = no pain relief, 1= a little pain relief, 2 = some pain relief, 3 = a lot of pain relief, and 4 = complete pain relief.
Time Frame	Up to 12 hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment and had at least one PR observation up to 12 hours post initial dose of study medication.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	130	129
Least Squares Mean (Standard Error) [Score on a Scale]	3.73 (0.07)	3.45 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	A priori threshold for statistical significance = <0.05.
	Method	ANOVA
	Comments	Adjusted for treatment, period, sequence, patient (sequence), and baseline pain intensity (moderate or severe).
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95%; 0.10 to 0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	PID at Up to 24 Hours Following the Initial Dose
Description	PID during the 24 hours following the initial dose is defined as the maximum PID score recorded during first 24 hours after the initial dose of study medication. PID is evaluated on a scale from 0 to 3, with 0 = no pain, 1 = slight pain, 2 = moderate pain, and 3 = severe pain.
Time Frame	Baseline and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 20 and 24 hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment and had at least one PID observation up to 24 hours post initial dose of study medication.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	130	130
Least Squares Mean (Standard Error) [Score on a Scale]	2.36 (0.04)	2.25 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments	A priori threshold for statistical significance = <0.05.
	Method	ANOVA
	Comments	Adjusted for treatment, period, sequence, patient (sequence), and baseline pain intensity (moderate or severe).
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; 0.03 to 0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	PR at Up to 24 Hours Following the Initial Dose
Description	PR during the 24 hours following the initial dose is defined as the maximum PR score recorded during the first 24 hours after the initial dose of study medication. PR is evaluated on a scale of 0 to 4, with 0 = no pain relief, 1= a little pain relief, 2 = some pain relief, 3 = a lot of pain relief, and 4 = complete pain relief.
Time Frame	Up to 24 hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment and had at least one PR observation at up to 24 hours post initial dose of study medication.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	130	130
Least Squares Mean (Standard Error) [Score on a Scale]	3.88 (0.07)	3.62 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	A priori threshold for statistical significance = <0.05.
	Method	ANOVA
	Comments	Adjusted for treatment, period, sequence, patient (sequence), and baseline pain intensity (moderate or severe).
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.26
	Confidence Interval	(2-Sided) 95%; 0.08 to 0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Number of Participants With a Global Evaluation of Study Medication of Good, Very Good, or Excellent at 6 Hours After the Initial Dose
Description	At 6 hours following the initial dose. participants were asked to rate their perception of pain control as poor, fair, good, very good, or excellent. The number of participants that reported good, very good, or excellent pain control at 6 hours post initial dose were summed.
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment and completed the assessment at 6 hours post initial dose of study medication.

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	129	129
Number [Participants]	111 79.9%	103 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.112
	Comments	A priori threshold for statistical significance = <0.05.
	Method	Regression, Logistic
	Comments	Adjusted for treatment, period, and baseline pain intensity.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.60
	Confidence Interval	(2-Sided) 95%; 0.90 to 2.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Number of Participants With a Global Evaluation of Study Medication of Good, Very Good, or Excellent at 24 Hours After the Initial Dose
Description	At 24 hours following the initial dose of study medication, participants were asked to rate their perception of pain control as poor, fair, good, very good, or excellent. The number of participants that reported good, very good, or excellent pain control at 24 hours post initial dose were summed.
Time Frame	24 Hours

Outcome Measure Data

Analysis Population Description

The population consisted of all participants that received at least one dose of study treatment and completed the assessment at 24 hours post initial dose of study medication

Arm/Group Title	Etoricoxib 120 mg	Ibuprofen up to 2400 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose.	Ibuprofen 600 mg (three 200-mg capsules) given orally up to four times a day as needed, for a maximum of 2400 mg/day.
Measure Participants	129	129
Number [Participants]	113 81.3%	101 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etoricoxib 120 mg, Ibuprofen up to 2400 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments	A priori threshold for statistical significance = <0.05.
	Method	Regression, Logistic
	Comments	Adjusted for treatment, period, and baseline pain intensity.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.97
	Confidence Interval	(2-Sided) 95%; 1.12 to 3.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From the time of the initial (first) dose of study medication up to 14 days after last dose of study medication.
Adverse Event Reporting Description	The safety population consisted of all randomized participants who received at least 1 dose of study treatment in at least 1 treatment cycle. For each treatment cycle, participants were to be included in the study treatment they actually received for the analysis of safety data.
Arm/Group Title	Etoricoxib 120 mg / Ibuprofen up to 2400 mg/Daily		Ibuprofen up to 2400 mg / Etoricoxib 120 mg
Arm/Group Description	Etoricoxib 120 mg tablet given orally for one dose in menstrual cycle 1. In menstrual cycle 2, ibuprofen was administered at a dose of 600 mg every 4 hours as needed up to 2400 mg/day.		Ibuprofen 600 mg given orally up to four times a day as needed, for a maximum of 2400 mg/day in menstrual cycle 1. In menstrual cycle 2, etoricoxib was administered at a dose of 120 mg daily.
All Cause Mortality
	Etoricoxib 120 mg / Ibuprofen up to 2400 mg/Daily		Ibuprofen up to 2400 mg / Etoricoxib 120 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Etoricoxib 120 mg / Ibuprofen up to 2400 mg/Daily		Ibuprofen up to 2400 mg / Etoricoxib 120 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/69 (0%)		0/70 (0%)
Other (Not Including Serious) Adverse Events
	Etoricoxib 120 mg / Ibuprofen up to 2400 mg/Daily		Ibuprofen up to 2400 mg / Etoricoxib 120 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/69 (0%)		0/70 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. The sponsor review can be expedited to meet publication timelines.