Clinical trial NCT01980940: The Single Dose Pharmacokinetics of Two and Proof of Efficacy of One New Etoricoxib Gel Formulation in Participants With Osteoarthritis (MK-0663-168)
Official title: A Study to Assess the Single Dose Pharmacokinetics of Two and Proof of Efficacy of One New Etoricoxib Gel Formulation in Osteoarthritis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Osteoarthritis Pain
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2013-11-11
Enrollment: 70
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Study Part 1: Maximum Concentration (Cmax) of ETOR After Single Dosing
timeFrame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application
measure: Study Part 1: Time to Maximum Concentration (Tmax) of ETOR After Single Dosing
timeFrame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application
measure: Study Part 1: Area Under the Concentration-time Curve of ETOR From Time 0 to Last (AUC0-last) After Single Dosing
timeFrame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application
measure: 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
timeFrame: Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14
Secondary outcomes:
measure: Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale
timeFrame: Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14
measure: Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Physical Functioning Scale
timeFrame: Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14
measure: Study Part 2: Percentage of Participants by Category on Patient Global Assessment of Response to Therapy (PGART)
timeFrame: Day 2, Day 4, Day 7, Day 11, Day 14, post-trial (up to Day 28)
measure: Study Parts 1 and 2: Number of Participants Who Experienced at Least One Adverse Event
timeFrame: Study Part 1: up to Day 47; Study Part 2: up to Day 28
measure: Study Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
timeFrame: Study Part 1: up to Day 47; Study Part 2: up to Day 28
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: