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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
70
Etoricoxib 75 mg 4% DMSO gel applied topically.
Etoricoxib 75 4% PG gel applied topically.
Etoricoxib 150 mg 4% DMSO gel applied topically.
Etoricoxib 150 mg 4% PG gel applied topically.
Etoricoxib 163 mg 4% DMSO gel applied topically
Placebo gel applied topically.
Etoricoxib 50 mg 4% DMSO gel applied topically.
Matching Placebo to Etoricoxib 50 mg 4% DMSO gel applied topically.
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
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
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
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
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
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
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)
Study Parts 1 and 2: Number of Participants Who Experienced at Least One Adverse Event
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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
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