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

June 5, 2024 updated by: Organon and Co

A Study to Assess the Single Dose Pharmacokinetics of Two and Proof of Efficacy of One New Etoricoxib Gel Formulation in Osteoarthritis Patients

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
70

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Etoricoxib 75 mg 4% DMSO Gel
Etoricoxib 75 mg 4% DMSO gel applied topically.
Drug: Etoricoxib 75 mg 4% PG Gel
Etoricoxib 75 4% PG gel applied topically.
Drug: Etoricoxib 150 mg 4% DMSO Gel
Etoricoxib 150 mg 4% DMSO gel applied topically.
Drug: Etoricoxib 150 mg 4% PG Gel
Etoricoxib 150 mg 4% PG gel applied topically.
Experimental: 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.
Drug: Etoricoxib 75 mg 4% DMSO Gel
Etoricoxib 75 mg 4% DMSO gel applied topically.
Drug: Etoricoxib 75 mg 4% PG Gel
Etoricoxib 75 4% PG gel applied topically.
Drug: Etoricoxib 150 mg 4% DMSO Gel
Etoricoxib 150 mg 4% DMSO gel applied topically.
Drug: Etoricoxib 150 mg 4% PG Gel
Etoricoxib 150 mg 4% PG gel applied topically.
Experimental: 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.
Drug: Etoricoxib 75 mg 4% DMSO Gel
Etoricoxib 75 mg 4% DMSO gel applied topically.
Drug: Etoricoxib 75 mg 4% PG Gel
Etoricoxib 75 4% PG gel applied topically.
Drug: Etoricoxib 150 mg 4% DMSO Gel
Etoricoxib 150 mg 4% DMSO gel applied topically.
Drug: Etoricoxib 150 mg 4% PG Gel
Etoricoxib 150 mg 4% PG gel applied topically.
Experimental: 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.
Drug: Etoricoxib 75 mg 4% DMSO Gel
Etoricoxib 75 mg 4% DMSO gel applied topically.
Drug: Etoricoxib 75 mg 4% PG Gel
Etoricoxib 75 4% PG gel applied topically.
Drug: Etoricoxib 150 mg 4% DMSO Gel
Etoricoxib 150 mg 4% DMSO gel applied topically.
Drug: Etoricoxib 150 mg 4% PG Gel
Etoricoxib 150 mg 4% PG gel applied topically.
Experimental: 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.
Drug: Etoricoxib 75 mg 4% DMSO Gel
Etoricoxib 75 mg 4% DMSO gel applied topically.
Drug: Etoricoxib 75 mg 4% PG Gel
Etoricoxib 75 4% PG gel applied topically.
Drug: Etoricoxib 150 mg 4% DMSO Gel
Etoricoxib 150 mg 4% DMSO gel applied topically.
Drug: Etoricoxib 163 mg 4% DMSO gel
Etoricoxib 163 mg 4% DMSO gel applied topically
Other: 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.
Drug: Placebo
Placebo gel applied topically.
Experimental: 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.
Drug: Etoricoxib 50 mg 4% DMSO
Etoricoxib 50 mg 4% DMSO gel applied topically.
Placebo Comparator: 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.
Drug: Matching Placebo to Etoricoxib 50 mg 4% DMSO Gel
Matching Placebo to Etoricoxib 50 mg 4% DMSO gel applied topically.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Study Part 1: Maximum Concentration (Cmax) of ETOR After Single Dosing
Time Frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application
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
Time Frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application
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
Time Frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, 24, 36, 48, and 72 hours post-application
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
Time Frame: Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Study Part 2: Change From Baseline in Mean Participant Score on the WOMAC VA 3.1 Stiffness Scale
Time Frame: Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14
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.
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
Time Frame: Baseline (Day -1), Day 2, Day 4, Day 7, Day 11, Day 14
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)
Time Frame: Day 2, Day 4, Day 7, Day 11, Day 14, post-trial (up to Day 28)
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
Time Frame: 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.
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
Time Frame: 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.
Study Part 1: up to Day 47; Study Part 2: up to Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Organon and Co

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 23, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 26, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 26, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 5, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2013

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 11, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 27, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0663-168

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

  1. CSR Synopsis

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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