The Single Dose Pharmacokinetics of Two and Proof of Efficacy of One New Etoricoxib Gel Formulation in Participants With Osteoarthritis (MK-0663-168)
A Study to Assess the Single Dose Pharmacokinetics of Two and Proof of Efficacy of One New Etoricoxib Gel Formulation in Osteoarthritis Patients
1 other identifier
interventional
70
0 countries
N/A
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2013
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 5, 2013
CompletedFirst Posted
Study publicly available on registry
November 11, 2013
CompletedStudy Start
First participant enrolled
December 23, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 26, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
November 26, 2014
CompletedResults Posted
Study results publicly available
December 11, 2015
CompletedJune 27, 2024
February 1, 2022
11 months
November 5, 2013
November 6, 2015
June 5, 2024
Conditions
Outcome Measures
Primary Outcomes (4)
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.
Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14
Secondary Outcomes (5)
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
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
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)
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
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
Study Arms (8)
Pt 1: ETOR 75 DMSO/ETOR 150 PG/ETOR 75 PG/ETOR 150 DMSO
EXPERIMENTALSingle-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
EXPERIMENTALSingle-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
EXPERIMENTALSingle-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
EXPERIMENTALSingle-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
EXPERIMENTALSingle-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)
OTHERParticipants 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
EXPERIMENTALEtoricoxib 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 COMPARATORMatching 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.
Interventions
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
Matching Placebo to Etoricoxib 50 mg 4% DMSO gel applied topically.
Eligibility Criteria
You may qualify if:
- 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;
- 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.
You may not qualify if:
- 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;
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Organon and Colead
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Vice President, Global Clinical Development
- Organization
- Merck Sharp & Dohme Corp.
Study Officials
- STUDY DIRECTOR
Medical Director
Merck Sharp & Dohme LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 5, 2013
First Posted
November 11, 2013
Study Start
December 23, 2013
Primary Completion
November 26, 2014
Study Completion
November 26, 2014
Last Updated
June 27, 2024
Results First Posted
December 11, 2015
Record last verified: 2022-02
Data Sharing
- IPD Sharing
- Will not share