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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pt 1: ETOR 75 DMSO/ETOR 150 PG/ETOR 75 PG/ETOR 150 DMSO | Experimental | 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. |
|
| Pt 1: ETOR 75 PG/ETOR 75 DMSO/ETOR 150 DMSO/ETOR 150 PG | Experimental | 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. |
|
| Pt 1: ETOR 150 DMSO/ETOR 75 PG/ETOR 150 PG/ETOR 75 DMSO | Experimental | 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. |
|
| Pt 1: ETOR 150 PG/ETOR 150 DMSO/ETOR 75 PG/ETOR 75 DMSO |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Etoricoxib 75 mg 4% DMSO Gel | Drug | Etoricoxib 75 mg 4% DMSO gel applied topically. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application |
| 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. | Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application |
| 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). | Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Experimental |
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. |
|
| Pt 1: ETOR OD/ ETOR 150 DMSO/ ETOR 75 DMSO/ ETOR 75 PG | Experimental | Single-dose etoricoxib 163 mg (4.30 mL) 4% DMSO gel (DMSO formulation administered in error/overdose [OD]), 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. |
|
| Pt 1: Placebo (Deviation) | Other | 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. |
|
| Pt 2: ETOR 50 DMSO | Experimental | Etoricoxib 50 mg (1.31 mL, 4% DMSO gel) applied topically twice daily to the affected knee for a period of 2 weeks. |
|
| Pt 2: Placebo | Placebo Comparator | 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. |
|
| Etoricoxib 75 mg 4% PG Gel | Drug | Etoricoxib 75 4% PG gel applied topically. |
|
| Etoricoxib 150 mg 4% DMSO Gel | Drug | Etoricoxib 150 mg 4% DMSO gel applied topically. |
|
| Etoricoxib 150 mg 4% PG Gel | Drug | Etoricoxib 150 mg 4% PG gel applied topically. |
|
| Etoricoxib 163 mg 4% DMSO gel | Drug | Etoricoxib 163 mg 4% DMSO gel applied topically |
|
| Placebo | Drug | Placebo gel applied topically. |
|
| Etoricoxib 50 mg 4% DMSO | Drug | Etoricoxib 50 mg 4% DMSO gel applied topically. |
|
| Matching Placebo to Etoricoxib 50 mg 4% DMSO Gel | Drug | Matching Placebo to Etoricoxib 50 mg 4% DMSO gel applied topically. |
|
| Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14 |
| Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14 |
| 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. | Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14 |
| 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'). | Day 2, Day 4, Day 7, Day 11, Day 14, post-trial (up to Day 28) |
| 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. | Study Part 1: up to Day 47; Study Part 2: up to Day 28 |
| 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. | Study Part 1: up to Day 47; Study Part 2: up to Day 28 |
| FG001 |
| 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | 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. |
| FG006 | 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. |
| FG007 | 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. |
| Treated |
|
| COMPLETED |
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| NOT COMPLETED |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | 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. |
| BG006 | 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. |
| BG007 | 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. |
| BG008 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | 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 | Posted | Least Squares Mean | 90% Confidence Interval | mg | Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application |
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| 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. | 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 | Posted | Median | Full Range | hour | Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application |
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| 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). | 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 | Posted | Least Squares Mean | 90% Confidence Interval | mg | Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application |
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| 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. | 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 | Posted | Mean | Standard Deviation | Units on a scale | Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14 |
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| 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. | 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 | Posted | Mean | Standard Deviation | Units on a scale | Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14 |
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| 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. | 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 | Posted | Mean | Standard Deviation | Units on a scale | Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14 |
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| 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'). | 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 | Posted | Number | Percentage of participants | Day 2, Day 4, Day 7, Day 11, Day 14, post-trial (up to Day 28) |
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| 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. | Safety analysis set defined as all treated participants (etoricoxib or placebo) based on the treatment received rather than the randomized assignment. | Posted | Number | Participants | Study Part 1: up to Day 47; Study Part 2: up to Day 28 |
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| 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. | Safety analysis set defined as all treated participants (etoricoxib or placebo) based on the treatment received rather than the randomized assignment. | Posted | Number | Participants | Study Part 1: up to Day 47; Study Part 2: up to Day 28 |
|
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ETOR 75 DMSO (Pt 1) | Single-dose etoricoxib 75 mg (1.97 mL) 4% DMSO gel applied topically. | 0 | 20 | 0 | 20 | ||
| EG001 | ETOR 75 PG (Pt 1) | Single-dose etoricoxib 75 mg (2.15 mL) 4% PG gel applied topically. | 0 | 20 | 0 | 20 | ||
| EG002 | ETOR 150 DMSO (Pt 1) | Single-dose etoricoxib 150 mg (3.94 mL) 4% DMSO gel applied topically. | 0 | 20 | 0 | 20 | ||
| EG003 | ETOR 150 PG (Pt 1) | Single-dose etoricoxib 150 mg (4.30 mL) 4% PG gel applied topically. | 0 | 18 | 1 | 18 | ||
| EG004 | ETOR OD (Pt 1) | Single-dose etoricoxib 163 mg (4.30 mL) 4% DMSO gel applied topically (DMSO formulation administered in overdose/error). | 0 | 2 | 2 | 2 | ||
| EG005 | Placebo (Pt 1) (Deviation) | Single dose placebo (1.97 mL or 3.94 mL) gel applied topically (placebo gel administered in error instead of active study drug formulation). | 0 | 2 | 0 | 2 | ||
| EG006 | ETOR 50 DMSO (Pt 2) | Etoricoxib 50 mg (1.31 mL, 4% DMSO gel) applied topically twice daily to the affected knee for a period of 2 weeks. | 0 | 24 | 2 | 24 | ||
| EG007 | Placebo (Pt 2) | 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. | 0 | 24 | 2 | 24 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cholecystocholangitis | Hepatobiliary disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D000077613 | Etoricoxib |
| D004121 | Dimethyl Sulfoxide |
| ID | Term |
|---|---|
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013454 | Sulfoxides |
Not provided
Not provided
| Male |
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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). |
| ANOVA |
| Treatment ratio |
| 7.30 |
| 2-Sided |
| 90 |
| 6.05 |
| 8.81 |
| Superiority or Other (legacy) |
| 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). | ANOVA | Treatment ratio | 0.45 | 2-Sided | 90 | 0.38 | 0.55 | Superiority or Other (legacy) |
| 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). | ANOVA | Treatment ratio | 0.65 | 2-Sided | 90 | 0.51 | 0.83 | Superiority or Other (legacy) |
| OG004 | ETOR OD | Single-dose etoricoxib 163 mg (4.30 mL) 4% DMSO gel applied topically (DMSO formulation administered in overdose/error). |
| OG005 | Placebo (Pt 1) (Deviation) | Single dose placebo (1.97 mL or 3.94 mL) gel applied topically (placebo gel administered in error instead of active study drug formulation). |
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| OG003 | ETOR 150 PG | Single-dose etoricoxib 150 mg (4.30 mL) 4% PG gel applied topically. |
| OG004 | ETOR OD | Single-dose etoricoxib 163 mg (4.30 mL) 4% DMSO gel applied topically (DMSO formulation administered in overdose/error). |
| OG005 | Placebo (Pt 1) (Deviation) | Single dose placebo (1.97 mL or 3.94 mL) gel applied topically (placebo gel administered in error instead of active study drug formulation). |
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| OG004 | ETOR OD (Pt 1) | Single-dose etoricoxib 163 mg (4.30 mL) 4% DMSO gel applied topically (DMSO formulation administered in overdose/error). |
| OG005 | Placebo (Pt 1) (Deviation) | Single dose placebo (1.97 mL or 3.94 mL) gel applied topically (placebo gel administered in error instead of active study drug formulation). |
| OG006 | ETOR 50 DMSO (Pt 2) | Etoricoxib 50 mg (1.31 mL, 4% DMSO gel) applied topically twice daily to the affected knee for a period of 2 weeks. |
| OG007 | Placebo (Pt 2) | 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. |
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Single-dose etoricoxib 150 mg (4.30 mL) 4% PG gel applied topically.
| OG004 | ETOR OD (Pt 1) | Single-dose etoricoxib 163 mg (4.30 mL) 4% DMSO gel applied topically (DMSO formulation administered in overdose/error). |
| OG005 | Placebo (Pt 1) (Deviation) | Single dose placebo (1.97 mL or 3.94 mL) gel applied topically (placebo gel administered in error instead of active study drug formulation). |
| OG006 | ETOR 50 DMSO (Pt 2) | Etoricoxib 50 mg (1.31 mL, 4% DMSO gel) applied topically twice daily to the affected knee for a period of 2 weeks. |
| OG007 | Placebo (Pt 2) | 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. |
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