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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,404
- 主要终点
- Time-Weighted Average Change From Baseline in Patient Global Assessment of Pain in Part 1 (Etoricoxib vs. Placebo)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Etoricoxib 60 mg (Drug)
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.
干预措施: Placebo to Etoricoxib 60 mg (Drug)
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.
干预措施: Etoricoxib 60 mg (Drug)
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.
干预措施: Placebo to Etoricoxib 60 mg (Drug)
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.
干预措施: Etoricoxib 90 mg (Drug)
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.
干预措施: Placebo to Etoricoxib 90 mg (Drug)
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.
干预措施: Placebo to Etoricoxib 60 mg (Drug)
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.
干预措施: Placebo to Etoricoxib 90 mg (Drug)
结局指标
主要结局
Time-Weighted Average Change From Baseline in Patient Global Assessment of Pain in Part 1 (Etoricoxib vs. Placebo)
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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.
次要结局
- 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)