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
Overview
- Phase
- Phase 3
- Intervention
- Etoricoxib 60 mg
- Conditions
- Arthritis, Rheumatoid
- Sponsor
- Organon and Co
- Enrollment
- 1404
- Primary Endpoint
- Time-Weighted Average Change From Baseline in Patient Global Assessment of Pain in Part 1 (Etoricoxib vs. Placebo)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Eligibility 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
Arms & Interventions
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.
Intervention: Etoricoxib 60 mg
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.
Intervention: Placebo to Etoricoxib 60 mg
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.
Intervention: Etoricoxib 60 mg
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.
Intervention: Placebo to Etoricoxib 60 mg
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.
Intervention: Etoricoxib 90 mg
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.
Intervention: Placebo to Etoricoxib 90 mg
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.
Intervention: Placebo to Etoricoxib 60 mg
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.
Intervention: Placebo to Etoricoxib 90 mg
Outcomes
Primary Outcomes
Time-Weighted Average Change From Baseline in Patient Global Assessment of Pain in Part 1 (Etoricoxib vs. Placebo)
Time Frame: Baseline and Week 6
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.
Percentage of Participants Who Experienced at Least One Adverse Event (AE)
Time Frame: Up to 112 days
An AE 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.
Time-Weighted Average Change From Baseline in DAS28-CRP in Part 1 (Etoricoxib vs. Placebo)
Time Frame: Baseline and Week 6
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.
Percentage of Participants Who Discontinued Study Drug Due to an AE
Time Frame: Up to Week 12
An AE 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.
Secondary Outcomes
- 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(Week 6 and Week 10 to Week 12)
- Time-Weighted Average Change From Baseline in DAS28-CRP in Part 1 (Etoricoxib 90 mg vs. Etoricoxib 60 mg)(Baseline and Week 6)
- Time-Weighted Average Change From Baseline in Patient Global Assessment of Pain in Part 1 (Etoricoxib 90 mg vs. Etoricoxib 60 mg)(Baseline and Week 6)