The Single Dose Pharmacokinetics of Two and Proof of Efficacy of One New Etoricoxib Gel Formulation in Participants With Osteoarthritis (MK-0663-168)

NCT ID: NCT01980940

Last Updated: 2024-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-23
• Study Completion Date: 2014-11-26

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.

Conditions

Osteoarthritis Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Etoricoxib 75 mg 4% DMSO Gel

Intervention Type: DRUG

Etoricoxib 75 mg 4% DMSO gel applied topically.

Etoricoxib 75 mg 4% PG Gel

Intervention Type: DRUG

Etoricoxib 75 4% PG gel applied topically.

Etoricoxib 150 mg 4% DMSO Gel

Intervention Type: DRUG

Etoricoxib 150 mg 4% DMSO gel applied topically.

Etoricoxib 150 mg 4% PG Gel

Intervention Type: DRUG

Etoricoxib 150 mg 4% PG gel applied topically.

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.

Group Type: EXPERIMENTAL

Etoricoxib 75 mg 4% DMSO Gel

Intervention Type: DRUG

Etoricoxib 75 mg 4% DMSO gel applied topically.

Etoricoxib 75 mg 4% PG Gel

Intervention Type: DRUG

Etoricoxib 75 4% PG gel applied topically.

Etoricoxib 150 mg 4% DMSO Gel

Intervention Type: DRUG

Etoricoxib 150 mg 4% DMSO gel applied topically.

Etoricoxib 150 mg 4% PG Gel

Intervention Type: DRUG

Etoricoxib 150 mg 4% PG gel applied topically.

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.

Group Type: EXPERIMENTAL

Etoricoxib 75 mg 4% DMSO Gel

Intervention Type: DRUG

Etoricoxib 75 mg 4% DMSO gel applied topically.

Etoricoxib 75 mg 4% PG Gel

Intervention Type: DRUG

Etoricoxib 75 4% PG gel applied topically.

Etoricoxib 150 mg 4% DMSO Gel

Intervention Type: DRUG

Etoricoxib 150 mg 4% DMSO gel applied topically.

Etoricoxib 150 mg 4% PG Gel

Intervention Type: DRUG

Etoricoxib 150 mg 4% PG gel applied topically.

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.

Group Type: EXPERIMENTAL

Etoricoxib 75 mg 4% DMSO Gel

Intervention Type: DRUG

Etoricoxib 75 mg 4% DMSO gel applied topically.

Etoricoxib 75 mg 4% PG Gel

Intervention Type: DRUG

Etoricoxib 75 4% PG gel applied topically.

Etoricoxib 150 mg 4% DMSO Gel

Intervention Type: DRUG

Etoricoxib 150 mg 4% DMSO gel applied topically.

Etoricoxib 150 mg 4% PG Gel

Intervention Type: DRUG

Etoricoxib 150 mg 4% PG gel applied topically.

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 \[OD\]), 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.

Group Type: EXPERIMENTAL

Etoricoxib 75 mg 4% DMSO Gel

Intervention Type: DRUG

Etoricoxib 75 mg 4% DMSO gel applied topically.

Etoricoxib 75 mg 4% PG Gel

Intervention Type: DRUG

Etoricoxib 75 4% PG gel applied topically.

Etoricoxib 150 mg 4% DMSO Gel

Intervention Type: DRUG

Etoricoxib 150 mg 4% DMSO gel applied topically.

Etoricoxib 163 mg 4% DMSO gel

Intervention Type: DRUG

Etoricoxib 163 mg 4% DMSO gel applied topically

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.

Group Type: OTHER

Placebo

Intervention Type: DRUG

Placebo gel applied topically.

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.

Group Type: EXPERIMENTAL

Etoricoxib 50 mg 4% DMSO

Intervention Type: DRUG

Etoricoxib 50 mg 4% DMSO gel applied topically.

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.

Group Type: PLACEBO_COMPARATOR

Matching Placebo to Etoricoxib 50 mg 4% DMSO Gel

Intervention Type: DRUG

Matching Placebo to Etoricoxib 50 mg 4% DMSO gel applied topically.

Interventions

Etoricoxib 75 mg 4% DMSO Gel

Etoricoxib 75 mg 4% DMSO gel applied topically.

Intervention Type: DRUG

Etoricoxib 75 mg 4% PG Gel

Etoricoxib 75 4% PG gel applied topically.

Intervention Type: DRUG

Etoricoxib 150 mg 4% DMSO Gel

Etoricoxib 150 mg 4% DMSO gel applied topically.

Intervention Type: DRUG

Etoricoxib 150 mg 4% PG Gel

Etoricoxib 150 mg 4% PG gel applied topically.

Intervention Type: DRUG

Etoricoxib 163 mg 4% DMSO gel

Etoricoxib 163 mg 4% DMSO gel applied topically

Intervention Type: DRUG

Placebo

Placebo gel applied topically.

Intervention Type: DRUG

Etoricoxib 50 mg 4% DMSO

Etoricoxib 50 mg 4% DMSO gel applied topically.

Intervention Type: DRUG

Matching Placebo to Etoricoxib 50 mg 4% DMSO Gel

Matching Placebo to Etoricoxib 50 mg 4% DMSO gel applied topically.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Organon and Co

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Other Identifiers

0663-168

Identifier Type: -

Identifier Source: org_study_id