Osteoarthritis Pain
Conditions
Brief summary
Study Part 1 is designed to assess the plasma pharmacokinetics of etoricoxib (ETOR) 4% dimethyl sulfoxide (DMSO) and propylene glycol (PG) formulations, each at 2 different doses, upon single-dose topical administration on the knee of osteoarthritis participants. Study Part 2 is designed to evaluate the efficacy of topical etoricoxib vs. placebo in the treatment of osteoarthritis of the knee. The primary hypothesis is that topical etoricoxib will be more effective than placebo in the treatment of osteoarthritis of the knee over 2 weeks of treatment as assessed by time-weighted average change from baseline on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analogue (VA) 3.0 pain subscale.
Detailed description
Part I of the study will consist of a single-dose, open-label, randomized, four-way cross over study with topical administration of etoricoxib gel on the knee of osteoarthritis participants. The washout between successive dose administrations will be at least one week. Part 2 of the study will consist of double-blind, randomized, placebo-controlled, parallel groups, multiple dose, twice daily topical administration of etoricoxib or placebo gel on the knee of osteoarthritis participants for a period of two weeks.
Interventions
DRUGEtoricoxib 75 mg 4% DMSO Gel
Etoricoxib 75 mg 4% DMSO gel applied topically.
DRUGEtoricoxib 75 mg 4% PG Gel
Etoricoxib 75 4% PG gel applied topically.
DRUGEtoricoxib 150 mg 4% DMSO Gel
Etoricoxib 150 mg 4% DMSO gel applied topically.
DRUGEtoricoxib 150 mg 4% PG Gel
Etoricoxib 150 mg 4% PG gel applied topically.
DRUGEtoricoxib 163 mg 4% DMSO gel
Etoricoxib 163 mg 4% DMSO gel applied topically
DRUGPlacebo
Placebo gel applied topically.
DRUGEtoricoxib 50 mg 4% DMSO
Etoricoxib 50 mg 4% DMSO gel applied topically.
DRUGMatching Placebo to Etoricoxib 50 mg 4% DMSO Gel
Matching Placebo to Etoricoxib 50 mg 4% DMSO gel applied topically.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has diagnosis of osteoarthritis of the knee (tibio-femoral joint) for \>6 months based on clinical and radiographic criteria; * Has a diagnosis of American Rheumatology Association (ARA) functional Class I, II, or III; * The knee designated as the study joint must be the participant's primary source of pain/disability in the lower extremity. If both knees are affected, the most painful joint will be selected for evaluation for inclusion and clinical response; * Female participants of childbearing potential must demonstrate a serum beta human chorionic gonadotropin (β-hCG) level consistent with a non-gravid state at the screening visit and urine β-hCG at Day -1 prior to first dosing and agree to use adequate oral or barrier contraception or abstain from sexual contact at least 7 days prior to treatment and continuing through the treatment period or a discontinuation visit; * Willing to limit alcohol intake (beer 8 ounces, wine 4 ounces, liquor 1 ounce) to no more than 14 drinks a week (no more than 2 in a day) and to avoid unaccustomed strenuous physical activity (e.g., unaccustomed weight lifting, initiation of physical therapy) for the duration of the study; * Judged to be in general good health with the exception of osteoarthritis based on medical history, physical examination, and routine laboratory tests. * For Part 2, if the participant is a regular user of non-steroidal anti-inflammatory drugs (NSAIDs) including coxibs he/she must report a history of positive therapeutic benefit in osteoarthritis of the knee with NSAID/coxibs in the past; * For Part 2, participants must be taking a single NSAID on a regular basis and at a prescription strength for at least 30 days prior to study screening (regular basis is defined as at least 25 of the previous 30 days) for treatment of symptoms of osteoarthritis.
Exclusion criteria
* Has a concurrent medical/arthritic disease; * History of acute ligamentous or meniscal injury of the study joint within the previous 2 years or arthroscopy of the affected knee within 6 months prior to study entry; * Is a candidate for imminent joint replacement; * Has clinical or laboratory evidence of significant renal, gastrointestinal, pulmonary, hepatic, endocrine, neurological (apart from migraine), or other systemic disease that in the opinion of the investigator contraindicates the use of etoricoxib; * Has congestive heart failure with symptoms that occur at rest or minimal activity; * Has unstable angina that occurs at rest or with minimal activity; * Has uncontrolled hypertension (sitting diastolic blood pressure \>95 mm Hg, or sitting systolic blood pressure \>165 mm Hg); * Has a history of stroke or transient ischemic attack (TIA) within the previous 6 months; * Has a history of hepatitis/hepatic disease that has been active within the previous 2 years; * Has a history of neoplastic disease; * Is currently a user (including recreational use) of any illicit drugs, or has a history of drug or alcohol abuse within the past 5 years; * Is allergic of has hypersensitivity to aspirin, ibuprofen, rofecoxib, celecoxib, valdecoxib, other NSAIDs, acetaminophen, or sulfa drugs; * Has used intravenous, intramuscular, or oral corticosteroids within 1 month of study entry; * Has used glucosamine and/or chondroitin sulfate for \<6 months prior to study start; * Has used intra-articular steroids, HYALGAN™ (sodium hyaluronate, Sanofi Pharmaceuticals), or SYNVISC™ (hylan G-F 20, Wyeth-Ayerst Pharmaceuticals) to the study joint within 3 months of entry into the study or intra-articular steroids, HYALGAN™, or SYNVISC™ to any other joint within 1 month of study entry; * Has used topical, oral or systemic analgesic medications within 2 weeks of study entry and for the duration of the study; * Requires treatment with warfarin, heparin, high-dose aspirin (\>325 mg), or digoxin; * Has used Arcoxia® within 2 weeks of study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study Part 1: Maximum Concentration (Cmax) of ETOR After Single Dosing | Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application | Cmax determined for the period up to 72 hours post-single application. Descriptive statistics are expressed as the geometric least squares mean (GLSM). Cmax with value 0 included in calculation of GLSMs with a value of 0.5\*LLOQ (=0.5 h\*ng/ml). |
| Study Part 1: Time to Maximum Concentration (Tmax) of ETOR After Single Dosing | Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application | Tmax determined for the period up to 72 hours post-single application. |
| Study Part 1: Area Under the Concentration-time Curve of ETOR From Time 0 to Last (AUC0-last) After Single Dosing | Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application | Area under the observed concentration-time curve from time zero to the last quantifiable time point determined for the period up to 72 hours post-single application. The area was calculated according to the linear up/log down trapezoidal rule. AUC0-last is an estimate of total plasma exposure. Descriptive statistics are expressed as the GLSM. AUC with value 0 included in calculation of GLSMs with a value of 0.5\*LLOQ (=0.5 h\*ng/ml). |
| Study Part 2: Change From Baseline in Mean Participant Score on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analog (VA) 3.1 Pain Scale | Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14 | The WOMAC VA 3.1 Pain subscale is a self-administered questionnaire assessing lower extremity pain due to osteoarthritis that was completed by participants 2 to 3 hours post morning dose. The WOMAC Pain Subscale had five questions with answers to each item assessed on a 100 mm VA scale (0 = no pain; 100 = extreme pain). The score for each item was summed and the overall score ranged from 0 to 500 (increasing severity). The time weighted average up to day x was calculated as the sum of rectangles under the curve for successive intervals prior to day x as defined by timepoints at which assessments were made. The time weighted change from baseline was calculated. A negative mean change from baseline indicates improvement in pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale | Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14 | The WOMAC VA 3.1 Stiffness subscale is a self-administered questionnaire assessing lower extremity stiffness due to osteoarthritis that was completed by participants 2 to 3 hours post morning dose. The WOMAC Stiffness subscale had two questions with answers to each item assessed on a 100 mm VA scale (0 = no stiffness; 100 = extreme stiffness). The score for each item was summed and the overall score ranged from 0 to 200 (increasing severity). The time weighted average up to day x was calculated as the sum of rectangles under the curve for successive intervals prior to day x as defined by timepoints at which assessments were made. The time weighted change from baseline was calculated. A negative mean change from baseline indicates improvement in stiffness. |
| Study Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | Study Part 1: up to Day 47; Study Part 2: up to Day 28 | An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure. |
| Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale | Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14 | The WOMAC VA 3.1 Physical Functioning subscale is a self-administered questionnaire assessing lower extremity physical function due to osteoarthritis that was completed by participants 2 to 3 hours post morning dose. The WOMAC Physical Functioning subscale had 17 questions with answers to each item assessed on a 100 mm VA scale (0 = no difficulty; 100 = extreme difficulty). The score for each item was summed and the overall score ranged from 0 to 1700 (increasing severity). The time weighted average up to day x was calculated as the sum of rectangles under the curve for successive intervals prior to day x as defined by timepoints at which assessments were made. The time weighted change from baseline was calculated. A negative mean change from baseline indicates improvement in physical function. |
| Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 2, Day 4, Day 7, Day 11, Day 14, post-trial (up to Day 28) | The PGART is a self-administered questionnaire completed by participants. Participant assessment of response of arthritis to study medication was assessed on a 5-point Likert scale ('very well', 'well', 'fair', 'poor', and 'very poor'). |
| Study Parts 1 and 2: Number of Participants Who Experienced at Least One Adverse Event | Study Part 1: up to Day 47; Study Part 2: up to Day 28 | An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure. |
Participant flow
Pre-assignment details
Participants were screened for inclusion in the study over 4 weeks prior to first treatment. Two additional participants were screened for Study Part 1 but not randomized or treated due to screen failure.
Participants by arm
| Arm | Count |
|---|---|
| Pt 1: ETOR 75 DMSO/ETOR 150 PG/ETOR 75 PG/ETOR 150 DMSO Single-dose etoricoxib 75 mg (1.97 mL) 4% DMSO gel, followed by single-dose etoricoxib 150 mg (4.30 mL) 4% PG gel, followed by single-dose etoricoxib 75 mg (2.15 mL) 4% PG gel, followed by single-dose etoricoxib 150 mg (3.94 mL) 4% DMSO gel. All treatments were applied topically. | 5 |
| Pt 1: ETOR 75 PG/ETOR 75 DMSO/ETOR 150 DMSO/ETOR 150 PG Single-dose etoricoxib 75 mg (2.15 mL) 4% PG gel, followed by single-dose etoricoxib 75 mg (1.97 mL) 4% DMSO gel, followed by single-dose etoricoxib 150 mg (3.94 mL) 4% DMSO gel, followed by single-dose etoricoxib 150 mg (4.30 mL) 4% PG gel. All treatments were applied topically. | 5 |
| Pt 1: ETOR 150 DMSO/ETOR 75 PG/ETOR 150 PG/ETOR 75 DMSO Single-dose etoricoxib 150 mg (3.94 mL) 4% DMSO gel, followed by single-dose etoricoxib 75 mg (2.15 mL) 4% PG gel, followed by single-dose etoricoxib 150 mg (4.30 mL) 4% PG gel, followed by single-dose etoricoxib 75 mg (1.97 mL) 4% DMSO gel. All treatments were applied topically. | 5 |
| Pt 1: ETOR 150 PG/ETOR 150 DMSO/ETOR 75 PG/ETOR 75 DMSO Single-dose etoricoxib 150 mg (4.30 mL) 4% PG gel, followed by single-dose etoricoxib 150 mg (3.94 mL) 4% DMSO gel, followed by single-dose etoricoxib 75 mg (1.97 mL) 4% DMSO gel, followed by single-dose etoricoxib 75 mg (2.15 mL) 4% PG gel. All treatments were applied topically. | 3 |
| Pt 1: ETOR OD/ ETOR 150 DMSO/ ETOR 75 DMSO/ ETOR 75 PG Single-dose etoricoxib 163 mg (4.30 mL) 4% DMSO gel (DMSO formulation administered in error/overdose), followed by single-dose etoricoxib 150 mg (3.94 mL) 4% DMSO gel, followed by single-dose etoricoxib 75 mg (1.97 mL) 4% DMSO gel, followed by single-dose etoricoxib 75 mg (2.15 mL) 4% PG gel. All treatments were applied topically. | 2 |
| Pt 1: Placebo (Deviation) Participants randomized to a treatment sequence in Part 1 who received single dose placebo gel (1.97 or 3.94 mL) applied topically in error instead of active study drug and dropped out after the first treatment period in the sequence. Included in the safety assessments only. | 2 |
| Pt 2: ETOR 50 DMSO Etoricoxib 50 mg (1.31 mL, 4% DMSO gel) applied topically twice daily to the affected knee for a period of 2 weeks. | 24 |
| Pt 2: Placebo Matching placebo to etoricoxib 50 mg 1.31 mL 4% DMSO gel applied topically twice daily to the affected knee for a period of 2 weeks. | 24 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Pt 1: ETOR 75 DMSO/ETOR 150 PG/ETOR 75 PG/ETOR 150 DMSO | Pt 1: ETOR 75 PG/ETOR 75 DMSO/ETOR 150 DMSO/ETOR 150 PG | Pt 1: ETOR 150 DMSO/ETOR 75 PG/ETOR 150 PG/ETOR 75 DMSO | Pt 1: ETOR 150 PG/ETOR 150 DMSO/ETOR 75 PG/ETOR 75 DMSO | Pt 1: ETOR OD/ ETOR 150 DMSO/ ETOR 75 DMSO/ ETOR 75 PG | Pt 1: Placebo (Deviation) | Pt 2: ETOR 50 DMSO | Pt 2: Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 61.0 years STANDARD_DEVIATION 6.6 | 61.0 years STANDARD_DEVIATION 12.3 | 63.6 years STANDARD_DEVIATION 10.6 | 62.0 years STANDARD_DEVIATION 10 | 55.0 years STANDARD_DEVIATION 8.5 | 60.5 years STANDARD_DEVIATION 4.9 | 61.5 years STANDARD_DEVIATION 8.2 | 61.2 years STANDARD_DEVIATION 6.7 | 61.3 years STANDARD_DEVIATION 7.8 |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 0 Participants | 18 Participants | 15 Participants | 48 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 6 Participants | 9 Participants | 22 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 1 / 18 | 2 / 2 | 0 / 2 | 2 / 24 | 2 / 24 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 18 | 0 / 2 | 0 / 2 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Study Part 1: Area Under the Concentration-time Curve of ETOR From Time 0 to Last (AUC0-last) After Single Dosing
Area under the observed concentration-time curve from time zero to the last quantifiable time point determined for the period up to 72 hours post-single application. The area was calculated according to the linear up/log down trapezoidal rule. AUC0-last is an estimate of total plasma exposure. Descriptive statistics are expressed as the GLSM. AUC with value 0 included in calculation of GLSMs with a value of 0.5\*LLOQ (=0.5 h\*ng/ml).
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application
Population: PK analysis set defined as all participants treated with etoricoxib with sufficient PK data for reliable estimation of the PK parameter of interest (AUC0-last) without any protocol violation that interferes with PK data interpretation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETOR 75 DMSO | Study Part 1: Area Under the Concentration-time Curve of ETOR From Time 0 to Last (AUC0-last) After Single Dosing | 611.3 mg | 90% Confidence Interval 400.97 |
| ETOR 75 PG | Study Part 1: Area Under the Concentration-time Curve of ETOR From Time 0 to Last (AUC0-last) After Single Dosing | 65.6 mg | 90% Confidence Interval 112.83 |
| ETOR 150 DMSO | Study Part 1: Area Under the Concentration-time Curve of ETOR From Time 0 to Last (AUC0-last) After Single Dosing | 1309.7 mg | 90% Confidence Interval 686.34 |
| ETOR 150 PG | Study Part 1: Area Under the Concentration-time Curve of ETOR From Time 0 to Last (AUC0-last) After Single Dosing | 161.3 mg | 90% Confidence Interval 172.96 |
Comparison: The GLSMR and 90% confidence interval was calculated for AUC0-last after log transformation for the formulation comparison (ETOR 75 DMSO/ETOR 75 PG) using a linear mixed effect model with fixed effects terms for treatment and period and random effect for participants. AUC with value 0 included in calculation of GLSMs with a value of 0.5\*LLOQ (=0.5 h\*ng/ml).90% CI: [4.77, 18.18]ANOVA
Comparison: The GLSMR and 90% confidence interval was calculated for AUC0-last after log transformation for the formulation comparison (ETOR 150 DMSO/ETOR 150 PG) using a linear mixed effect model with fixed effects terms for treatment and period and random effect for participants. AUC with value 0 included in calculation of GLSMs with a value of 0.5\*LLOQ (=0.5 h\*ng/ml).90% CI: [6.39, 10.32]ANOVA
Comparison: The GLSMR and 90% confidence interval was calculated for AUC0-last after log transformation for the dose comparison (ETOR 75 DMSO/ETOR 150 DMSO) using a linear mixed effect model with fixed effects terms for treatment and period and random effect for participants. AUC with value 0 included in calculation of GLSMs with a value of 0.5\*LLOQ (=0.5 h\*ng/ml).90% CI: [0.39, 0.57]ANOVA
Comparison: The GLSMR and 90% confidence interval was calculated for AUC0-last after log transformation for the dose comparison (ETOR 75 PG/ETOR 150 PG) using a linear mixed effect model with fixed effects terms for treatment and period and random effect for participants. AUC with value 0 included in calculation of GLSMs with a value of 0.5\*LLOQ (=0.5 h\*ng/ml).90% CI: [0.21, 0.79]ANOVA
Primary
Study Part 1: Maximum Concentration (Cmax) of ETOR After Single Dosing
Cmax determined for the period up to 72 hours post-single application. Descriptive statistics are expressed as the geometric least squares mean (GLSM). Cmax with value 0 included in calculation of GLSMs with a value of 0.5\*LLOQ (=0.5 h\*ng/ml).
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application
Population: PK analysis set defined as all participants treated with etoricoxib with sufficient PK data for reliable estimation of the PK parameter of interest (Cmax) without any protocol violation that interferes with PK data interpretation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETOR 75 DMSO | Study Part 1: Maximum Concentration (Cmax) of ETOR After Single Dosing | 12.39 mg | 90% Confidence Interval 8.24 |
| ETOR 75 PG | Study Part 1: Maximum Concentration (Cmax) of ETOR After Single Dosing | 2.43 mg | 90% Confidence Interval 2.14 |
| ETOR 150 DMSO | Study Part 1: Maximum Concentration (Cmax) of ETOR After Single Dosing | 27.30 mg | 90% Confidence Interval 15.3 |
| ETOR 150 PG | Study Part 1: Maximum Concentration (Cmax) of ETOR After Single Dosing | 3.74 mg | 90% Confidence Interval 3.79 |
Comparison: The geometric least squares mean ratio (GLSMR) and 90% confidence interval was calculated for Cmax after log transformation for the formulation comparison (ETOR 75 DMSO/ETOR 75 PG) using a linear mixed effect model with fixed effects terms for treatment and period and random effect for participants. Cmax with value 0 included in calculation of GLSMs with a value of 0.5\*LLOQ (=0.5 h\*ng/ml).90% CI: [4.03, 6.42]ANOVA
Comparison: The GLSMR and 90% confidence interval was calculated for Cmax after log transformation for the formulation comparison (ETOR 150 DMSO/ETOR 150 PG) using a linear mixed effect model with fixed effects terms for treatment and period and random effect for participants. Cmax with value 0 included in calculation of GLSMs with a value of 0.5\*LLOQ (=0.5 h\*ng/ml).90% CI: [6.05, 8.81]ANOVA
Comparison: The GLSMR and 90% confidence interval was calculated for Cmax after log transformation for the dose comparison (ETOR 75 DMSO/ETOR 150 DMSO) using a linear mixed effect model with fixed effects terms for treatment and period and random effect for participants. Cmax with value 0 included in calculation of GLSMs with a value of 0.5\*LLOQ (=0.5 h\*ng/ml).90% CI: [0.38, 0.55]ANOVA
Comparison: The GLSMR and 90% confidence interval was calculated for Cmax after log transformation for the dose comparison (ETOR 75 PG/ETOR 150 PG) using a linear mixed effect model with fixed effects terms for treatment and period and random effect for participants. Cmax with value 0 included in calculation of GLSMs with a value of 0.5\*LLOQ (=0.5 h\*ng/ml).90% CI: [0.51, 0.83]ANOVA
Primary
Study Part 1: Time to Maximum Concentration (Tmax) of ETOR After Single Dosing
Tmax determined for the period up to 72 hours post-single application.
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application
Population: PK analysis set defined as all participants treated with etoricoxib with sufficient PK data for reliable estimation of the PK parameter of interest (Tmax) without any protocol violation that interferes with PK data interpretation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ETOR 75 DMSO | Study Part 1: Time to Maximum Concentration (Tmax) of ETOR After Single Dosing | 30.0 hour |
| ETOR 75 PG | Study Part 1: Time to Maximum Concentration (Tmax) of ETOR After Single Dosing | 48.0 hour |
| ETOR 150 DMSO | Study Part 1: Time to Maximum Concentration (Tmax) of ETOR After Single Dosing | 24.0 hour |
| ETOR 150 PG | Study Part 1: Time to Maximum Concentration (Tmax) of ETOR After Single Dosing | 48 hour |
| ETOR OD | Study Part 1: Time to Maximum Concentration (Tmax) of ETOR After Single Dosing | 36.0 hour |
Primary
Study Part 2: Change From Baseline in Mean Participant Score on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analog (VA) 3.1 Pain Scale
The WOMAC VA 3.1 Pain subscale is a self-administered questionnaire assessing lower extremity pain due to osteoarthritis that was completed by participants 2 to 3 hours post morning dose. The WOMAC Pain Subscale had five questions with answers to each item assessed on a 100 mm VA scale (0 = no pain; 100 = extreme pain). The score for each item was summed and the overall score ranged from 0 to 500 (increasing severity). The time weighted average up to day x was calculated as the sum of rectangles under the curve for successive intervals prior to day x as defined by timepoints at which assessments were made. The time weighted change from baseline was calculated. A negative mean change from baseline indicates improvement in pain.
Time frame: Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14
Population: Full analysis set (FAS) defined as all treated participants (etoricoxib or placebo) without major entry criteria violation and with at least one valid post-baseline primary efficacy assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analog (VA) 3.1 Pain Scale | BL to Day 2 | -24.21 Units on a scale | Standard Deviation 76.88 |
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analog (VA) 3.1 Pain Scale | BL to Day 4 | -34.29 Units on a scale | Standard Deviation 69.15 |
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analog (VA) 3.1 Pain Scale | BL to Day 7 | -45.81 Units on a scale | Standard Deviation 67.92 |
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analog (VA) 3.1 Pain Scale | BL to Day 11 | -59.42 Units on a scale | Standard Deviation 71.12 |
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analog (VA) 3.1 Pain Scale | BL to Day 14 | -69.60 Units on a scale | Standard Deviation 75.81 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analog (VA) 3.1 Pain Scale | BL to Day 4 | -43.92 Units on a scale | Standard Deviation 94.81 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analog (VA) 3.1 Pain Scale | BL to Day 2 | -37.21 Units on a scale | Standard Deviation 101.77 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analog (VA) 3.1 Pain Scale | BL to Day 11 | -63.60 Units on a scale | Standard Deviation 90.99 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analog (VA) 3.1 Pain Scale | BL to Day 14 | -72.60 Units on a scale | Standard Deviation 91.35 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Visual Analog (VA) 3.1 Pain Scale | BL to Day 7 | -54.11 Units on a scale | Standard Deviation 94.11 |
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 2 in the WOMAC VA 3.1 pain subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 2 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.211390% CI: [-63.6, 8.9]constrained longitudinal data analysis
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 4 in the WOMAC VA 3.1 pain subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 4 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.254890% CI: [-55.7, 10.3]constrained longitudinal data analysis
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 7 in the WOMAC VA 3.1 pain subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 7 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.28890% CI: [-54.9, 12]constrained longitudinal data analysis
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 11 in the WOMAC VA 3.1 pain subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 11 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.370990% CI: [-50.4, 15.1]constrained longitudinal data analysis
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 14 in the WOMAC VA 3.1 pain subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 14 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.388390% CI: [-50.5, 16]constrained longitudinal data analysis
Secondary
Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale
The WOMAC VA 3.1 Physical Functioning subscale is a self-administered questionnaire assessing lower extremity physical function due to osteoarthritis that was completed by participants 2 to 3 hours post morning dose. The WOMAC Physical Functioning subscale had 17 questions with answers to each item assessed on a 100 mm VA scale (0 = no difficulty; 100 = extreme difficulty). The score for each item was summed and the overall score ranged from 0 to 1700 (increasing severity). The time weighted average up to day x was calculated as the sum of rectangles under the curve for successive intervals prior to day x as defined by timepoints at which assessments were made. The time weighted change from baseline was calculated. A negative mean change from baseline indicates improvement in physical function.
Time frame: Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14
Population: FAS defined as all treated participants (etoricoxib or placebo) without major entry criteria violation and with at least one valid post-baseline primary efficacy assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale | BL to Day 4 | -147.71 Units on a scale | Standard Deviation 183.07 |
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale | BL to Day 11 | -214.87 Units on a scale | Standard Deviation 203.95 |
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale | BL to Day 7 | -172.94 Units on a scale | Standard Deviation 186.22 |
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale | BL to Day 14 | -250.82 Units on a scale | Standard Deviation 218.72 |
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale | BL to Day 2 | -117.13 Units on a scale | Standard Deviation 200.38 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale | BL to Day 14 | -280.29 Units on a scale | Standard Deviation 233.39 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale | BL to Day 2 | -153.54 Units on a scale | Standard Deviation 278.66 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale | BL to Day 4 | -171.35 Units on a scale | Standard Deviation 272.51 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale | BL to Day 7 | -199.88 Units on a scale | Standard Deviation 265.29 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale | BL to Day 11 | -245.05 Units on a scale | Standard Deviation 238.05 |
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 2 in the WOMAC VA 3.1 physical function subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 2 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.447790% CI: [-166.8, 62.3]constrained longitudinal data analysis
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 4 in the WOMAC VA 3.1 physical function subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 4 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.608490% CI: [-143.6, 76.1]constrained longitudinal data analysis
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 7 in the WOMAC VA 3.1 physical function subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 7 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.592690% CI: [-144.7, 74.4]constrained longitudinal data analysis
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 11 in the WOMAC VA 3.1 physical function subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 11 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.502290% CI: [-147.2, 62.6]constrained longitudinal data analysis
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 14 in the WOMAC VA 3.1 physical function subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 14 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.512590% CI: [-149, 64.9]constrained longitudinal data analysis
Secondary
Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale
The WOMAC VA 3.1 Stiffness subscale is a self-administered questionnaire assessing lower extremity stiffness due to osteoarthritis that was completed by participants 2 to 3 hours post morning dose. The WOMAC Stiffness subscale had two questions with answers to each item assessed on a 100 mm VA scale (0 = no stiffness; 100 = extreme stiffness). The score for each item was summed and the overall score ranged from 0 to 200 (increasing severity). The time weighted average up to day x was calculated as the sum of rectangles under the curve for successive intervals prior to day x as defined by timepoints at which assessments were made. The time weighted change from baseline was calculated. A negative mean change from baseline indicates improvement in stiffness.
Time frame: Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14
Population: FAS defined as all treated participants (etoricoxib or placebo) without major entry criteria violation and with at least one valid post-baseline primary efficacy assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale | BL to Day 7 | -19.34 Units on a scale | Standard Deviation 35.75 |
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale | BL to Day 2 | -9.17 Units on a scale | Standard Deviation 37.44 |
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale | BL to Day 11 | -24.44 Units on a scale | Standard Deviation 34.6 |
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale | BL to Day 14 | -29.22 Units on a scale | Standard Deviation 36.64 |
| ETOR 75 DMSO | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale | BL to Day 4 | -14.69 Units on a scale | Standard Deviation 35.23 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale | BL to Day 14 | -30.52 Units on a scale | Standard Deviation 34.33 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale | BL to Day 11 | -26.87 Units on a scale | Standard Deviation 35.26 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale | BL to Day 2 | -16.79 Units on a scale | Standard Deviation 41.86 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale | BL to Day 7 | -23.08 Units on a scale | Standard Deviation 37.53 |
| ETOR 75 PG | Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale | BL to Day 4 | -18.79 Units on a scale | Standard Deviation 39.29 |
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 2 in the WOMAC VA 3.1 stiffness subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 2 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.138390% CI: [-29.7, 1.6]constrained longitudinal data analysis
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 4 in the WOMAC VA 3.1 stiffness subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 4 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.23890% CI: [-24.9, 4.2]constrained longitudinal data analysis
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 7 in the WOMAC VA 3.1 stiffness subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 7 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.269190% CI: [-23.9, 4.8]constrained longitudinal data analysis
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 11 in the WOMAC VA 3.1 stiffness subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 11 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.324690% CI: [-21.8, 5.6]constrained longitudinal data analysis
Comparison: Treatment difference in mean time-weighted average change from baseline to Day 14 in the WOMAC VA 3.1 stiffness subscale score (ETOR 50 DMSO - Placebo \[Pt 2\]) was evaluated using a constrained longitudinal data analysis model that included baseline measurements and time-weighted average at Day 14 in the response variable. The model included terms of visit, visit-by-treatment, and treatment.p-value: 0.388190% CI: [-20.9, 6.6]constrained longitudinal data analysis
Secondary
Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART)
The PGART is a self-administered questionnaire completed by participants. Participant assessment of response of arthritis to study medication was assessed on a 5-point Likert scale ('very well', 'well', 'fair', 'poor', and 'very poor').
Time frame: Day 2, Day 4, Day 7, Day 11, Day 14, post-trial (up to Day 28)
Population: FAS defined as all treated participants (etoricoxib or placebo) without major entry criteria violation and with at least one valid post-baseline primary efficacy assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 4: Very well | 0.0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 4: Poor | 29.2 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 7: Well | 25.0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 14: Poor | 4.2 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 2: Very well | 0.0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 2: Well | 20.8 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 2: Fair | 25.0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 2: Poor | 37.5 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 2: Very poor | 16.7 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 4: Well | 20.8 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 4: Fair | 45.8 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 4: Very poor | 4.2 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 7: Very well | 0.0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 7: Fair | 50.0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 7: Poor | 25.0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 7: Very poor | 0.0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 11: Very well | 0.0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 11: Well | 37.5 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 11: Fair | 45.8 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 11: Poor | 16.7 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 11: Very poor | 0.0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 14: Very well | 0.0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 14: Well | 54.2 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 14: Fair | 41.7 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 14: Very poor | 0.0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Post-trial: Very well | 8.3 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Post-trial: Well | 62.5 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Post-trial: Fair | 29.2 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Post-trial: Poor | 0 Percentage of participants |
| ETOR 75 DMSO | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Post-trial: Very poor | 0.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 14: Well | 50.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 4: Very well | 0.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 7: Very poor | 0.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 4: Poor | 25.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Post-trial: Well | 50.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 11: Very well | 0.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 14: Poor | 8.3 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 14: Fair | 33.3 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 2: Very well | 0.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 11: Well | 50.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 2: Well | 33.3 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Post-trial: Poor | 12.5 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 2: Fair | 25.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 11: Fair | 37.5 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 2: Poor | 33.3 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 14: Very poor | 0.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 2: Very poor | 8.3 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 11: Poor | 12.5 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 4: Well | 33.3 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Post-trial: Fair | 29.2 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 4: Fair | 37.5 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 11: Very poor | 0.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 4: Very poor | 4.2 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Post-trial: Very well | 8.3 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 7: Very well | 0.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 7: Well | 37.5 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 14: Very well | 8.3 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 7: Fair | 37.5 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Post-trial: Very poor | 0.0 Percentage of participants |
| ETOR 75 PG | Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART) | Day 7: Poor | 25.0 Percentage of participants |
Comparison: Treatment comparison of Day 2 PGART frequencies (ETOR 50 DMSO vs Placebo \[Pt 2\]) was performed using a two-sided Jonckheere-Terpstra test.p-value: 0.2632Jonckheere-Terpstra test
Comparison: Treatment comparison of Day 4 PGART frequencies (ETOR 50 DMSO vs Placebo \[Pt 2\]) was performed using a two-sided Jonckheere-Terpstra test.p-value: 0.4703Jonckheere-Terpstra test
Comparison: Treatment comparison of Day 7 PGART frequencies (ETOR 50 DMSO vs Placebo \[Pt 2\]) was performed using a two-sided Jonckheere-Terpstra test.p-value: 0.5507Jonckheere-Terpstra test
Comparison: Treatment comparison of Day 11 PGART frequencies (ETOR 50 DMSO vs Placebo \[Pt 2\]) was performed using a two-sided Jonckheere-Terpstra test.p-value: 0.3992Jonckheere-Terpstra test
Comparison: Treatment comparison of Day 14 PGART frequencies (ETOR 50 DMSO vs Placebo \[Pt 2\]) was performed using a two-sided Jonckheere-Terpstra test.p-value: 0.6626Jonckheere-Terpstra test
Comparison: Treatment comparison of post-trial PGART frequencies (ETOR 50 DMSO vs Placebo \[Pt 2\]) was performed using a two-sided Jonckheere-Terpstra test.p-value: 0.315Jonckheere-Terpstra test
Secondary
Study Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure.
Time frame: Study Part 1: up to Day 47; Study Part 2: up to Day 28
Population: Safety analysis set defined as all treated participants (etoricoxib or placebo) based on the treatment received rather than the randomized assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETOR 75 DMSO | Study Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| ETOR 75 PG | Study Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| ETOR 150 DMSO | Study Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| ETOR 150 PG | Study Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| ETOR OD | Study Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Placebo (Pt 1) (Deviation) | Study Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| ETOR 50 DMSO (Pt 2) | Study Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Placebo (Pt 2) | Study Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
Secondary
Study Parts 1 and 2: Number of Participants Who Experienced at Least One Adverse Event
An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure.
Time frame: Study Part 1: up to Day 47; Study Part 2: up to Day 28
Population: Safety analysis set defined as all treated participants (etoricoxib or placebo) based on the treatment received rather than the randomized assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETOR 75 DMSO | Study Parts 1 and 2: Number of Participants Who Experienced at Least One Adverse Event | 1 Participants |
| ETOR 75 PG | Study Parts 1 and 2: Number of Participants Who Experienced at Least One Adverse Event | 1 Participants |
| ETOR 150 DMSO | Study Parts 1 and 2: Number of Participants Who Experienced at Least One Adverse Event | 1 Participants |
| ETOR 150 PG | Study Parts 1 and 2: Number of Participants Who Experienced at Least One Adverse Event | 1 Participants |
| ETOR OD | Study Parts 1 and 2: Number of Participants Who Experienced at Least One Adverse Event | 2 Participants |
| Placebo (Pt 1) (Deviation) | Study Parts 1 and 2: Number of Participants Who Experienced at Least One Adverse Event | 0 Participants |
| ETOR 50 DMSO (Pt 2) | Study Parts 1 and 2: Number of Participants Who Experienced at Least One Adverse Event | 6 Participants |
| Placebo (Pt 2) | Study Parts 1 and 2: Number of Participants Who Experienced at Least One Adverse Event | 5 Participants |