A Two-Part, 12-Week Study of Etoricoxib as a Treatment for Rheumatoid Arthritis (RA) (MK-0663-107)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01208181
First received: September 22, 2010
Last updated: May 5, 2015
Last verified: May 2015
  Purpose

This is a 2-part (6 weeks duration for each part), randomized, double-blind, placebo-controlled study in participants with rheumatoid arthritis. The hypothesis is that etoricoxib (60 mg and 90 mg) administration will demonstrate superior efficacy compared to placebo after 6 weeks of treatment, as measured by the greater mean improvement from baseline in the Disease Activity Score C-Reactive Protein (DAS-28 CRP), and by the greater mean improvement in Patient Global Assessment of Pain (PGAP) from baseline over 6 weeks of treatment. Additionally, the added benefit of increasing the dose of etoricoxib from 60 mg to 90 mg will be assessed in the second part of the study.


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: Etoricoxib 60 mg
Drug: Etoricoxib 90 mg
Drug: Placebo to Etoricoxib 60 mg
Drug: Placebo to Etoricoxib 90 mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Two-Part, Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial to Assess the Relative Efficacy and Tolerability of Two Doses of MK‑0663/Etoricoxib in Patients With Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Time-Weighted Average Change From Baseline in DAS28-CRP in Part 1 (Etoricoxib vs. Placebo) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    Disease Activity Score Using C-Reactive Protein [DAS28-CRP] (0 - 10 Range). The DAS28-CRP index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity, and C-reactive protein (CRP). For each observation (Baseline, Week 2, 4, 6, 10, 12), components were combined into a single DAS28-CRP score using the following algorithm: 0.56*square root (sqrt) (tender joint count [28])+0.28*sqrt(swollen joint count [28] )+0.36* ln(crp+1) + 0.014* Patient Global Assessment of Disease Activity + 0.96. The primary objectives of the study compared the efficacy of etoricoxib (90 mg, 60 mg) to placebo in Part 1 of this study so data for only these 3 arms are displayed.

  • Time-Weighted Average Change From Baseline in Patient Global Assessment of Pain in Part 1 (Etoricoxib vs. Placebo) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    A participant overall assessment of pain on a visual analog scale (VAS) was assessed with a question concerning the amount of pain due to arthritis during the past 48 hours. Pain was assessed on an 100 mm VAS scale with a left-hand marker "no pain" (0 mm) or right-hand marker "extreme pain" (100 mm). The primary objectives of the study compared the efficacy of etoricoxib (90 mg, 60 mg) to placebo in Part 1 of this study so data for only these 3 arms are displayed.


Secondary Outcome Measures:
  • Time-Weighted Average Change From Baseline in DAS28-CRP in Part 1 (Etoricoxib 90 mg vs. Etoricoxib 60 mg) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    Disease Activity Score Using C-Reactive Protein [DAS28-CRP] (0 - 10 Range). The DAS28-CRP index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity, and C-reactive protein (CRP). For each observation (Baseline, Week 2, 4, 6, 10, 12), components were combined into a single DAS28-CRP score using the following algorithm: 0.56*square root (sqrt) (tender joint count [28])+0.28*sqrt(swollen joint count [28] )+0.36* ln(crp+1) + 0.014* Patient Global Assessment of Disease Activity + 0.96. The key secondary objectives compared the relative efficacy between etoricoxib 90 mg and 60 mg in Part 1 of this study so data for only these 2 arms are displayed.

  • Time-Weighted Average Change From Baseline in Patient Global Assessment of Pain in Part 1 (Etoricoxib 90 mg vs. Etoricoxib 60 mg) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    A participant overall assessment of pain on a visual analog scale (VAS) was assessed with a question concerning the amount of pain due to arthritis during the past 48 hours. Pain was assessed on an 100 mm VAS scale with a left-hand marker "no pain" (0 mm) or right-hand marker "extreme pain" (100 mm). The key secondary objectives compared the relative efficacy between etoricoxib 90 mg and 60 mg in Part 1 of this study so data for only these 2 arms are displayed.

  • Average Change From Week 6 in Patient Global Assessment of Pain Over Weeks 10 and 12 in Part 2 Among Pain Inadequate Responders From Part 1 [ Time Frame: Week 6 and Week 10 to Week 12 ] [ Designated as safety issue: No ]
    A participant overall assessment of pain on a visual analog scale (VAS) was assessed with a question concerning the amount of pain due to arthritis during the past 48 hours. Pain was assessed on an 100 mm VAS scale with a left-hand marker "no pain" (0 mm) or right-hand marker "extreme pain" (100 mm). In those participants who were considered inadequate responders to etoricoxib 60 mg in Part 1 (defined as a participant with <50% improvement from baseline in PGAP [VAS] at Week 6), the incremental benefit of increasing the etoricoxib dose from 60 mg (in Part 1) to 90 mg (in Part 2) compared to remaining on 60 mg in Part 2 was evaluated via average change from Week 6 over Weeks 10 and 12 in Patient Global Assessment of Pain score. Therefore, data for only these 2 arms are displayed.


Enrollment: 1404
Study Start Date: September 2010
Study Completion Date: July 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Etoricoxib 60 mg/Etoricoxib 60 mg
The etoricoxib 60 mg/etoricoxib 60 mg treatment sequence will receive etoricoxib 60 mg tablets administered orally once daily for 6 weeks in Part 1 and Part 2 of the study.
Drug: Etoricoxib 60 mg
One tablet orally once daily for 6 weeks.
Other Name: MK-0663
Drug: Placebo to Etoricoxib 60 mg
One tablet orally once daily for 6 weeks.
Experimental: Etoricoxib 60 mg/Etoricoxib 90 mg
The etoricoxib 60 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 60 mg tablets administered orally once daily for 6 weeks in Part 1 and etoricoxib 90 mg tablets administered orally once daily for 6 weeks in Part 2 of the study.
Drug: Etoricoxib 60 mg
One tablet orally once daily for 6 weeks.
Other Name: MK-0663
Drug: Placebo to Etoricoxib 60 mg
One tablet orally once daily for 6 weeks.
Experimental: Etoricoxib 90 mg
The etoricoxib 90 mg treatment sequence will receive etoricoxib 90 mg tablets administered orally once daily for 6 weeks in Part 1 and will not participate in Part 2 of the study.
Drug: Etoricoxib 90 mg
One tablet orally once daily for 6 weeks.
Other Name: MK-0663
Drug: Placebo to Etoricoxib 90 mg
One tablet orally once daily for 6 weeks
Placebo Comparator: Placebo
The placebo treatment sequence will receive matching placebo to etoricoxib tablets administered orally once daily for 6 weeks in Part 1 and will not participate in Part 2 of the study.
Drug: Placebo to Etoricoxib 60 mg
One tablet orally once daily for 6 weeks.
Drug: Placebo to Etoricoxib 90 mg
One tablet orally once daily for 6 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is male or female ≥ 18 years of age in general good health (other than RA)
  • Has an American College of Rheumatology Rheumatoid Clinical Response Criteria (ACR) Functional Class I, II, or III
  • Has a diagnosis of RA at least 6 months ago and was at least 16 years of age when diagnosed
  • Has a history of positive therapeutic benefit with nonsteroidal anti-inflammatory drugs (NSAIDs) and is taking an NSAID on a regular basis and at a therapeutic dose level and is not anticipated to undergo a change during the study

Exclusion Criteria:

  • Has a concurrent medical/arthritic disease that could confound or interfere with evaluation of efficacy
  • Has a history of gastric or biliary surgery (including gastric bypass surgery) or small intestine surgery that causes clinical malabsorption
  • Has an active peptic (gastric or duodenal) ulcer or history of inflammatory bowel disease
  • Has a confirmed medical diagnosis of ischemic heart disease, cerebrovascular disease, or peripheral artery occlusive disease
  • Class II-IV congestive heart failure
  • Has uncontrolled hypertension (systolic >160 mm Hg or diastolic > 90 mm Hg) at Visit 1 or Visit 2
  • Has a clinical diagnosis of hepatic insufficiency defined as Child-Pugh score ≥5
  • Has estimated glomerular filtration rate ≤30 mL/min
  • Has a history of neoplastic disease within 5 years (exceptions: basal cell carcinoma or carcinoma in situ of the cervix)
  • Is allergic to etoricoxib; history of a significant clinical or laboratory adverse experience associated with etoricoxib; hypersensitivity to aspirin or NSAIDs; or allergy to acetaminophen/paracetamol
  • Has a personal or family history of an inherited or acquired bleeding disorder
  • Requires oral corticosteroid therapy in excess of the equivalent of 10 mg daily of prednisone and/or have not been on a stable dose for at least 4 weeks prior to Visit 1 and/or whose dose is not expected to remain stable during the study
  • Treated with B-cell depleting therapies within the past 6 months or anticipate this treatment during this trial
  • Is a recreational or illicit drug use, or history within 5 years of drug or alcohol abuse/dependence;
  • Is morbidly obese (defined as body mass index ≥40 kg/m^2)
  • Is pregnant or breast feeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01208181

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01208181     History of Changes
Other Study ID Numbers: 0663-107, 2010-019871-31
Study First Received: September 22, 2010
Results First Received: May 5, 2015
Last Updated: May 5, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Etoricoxib
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 02, 2015