A Phase III, Two-Part, Randomized, Double-Blind, Active Comparator-Controlled, Multicenter Clinical Trial to Study the Relative Efficacy and Tolerability of Two Doses of MK-0663/Etoricoxib in Patients With Ankylosing Spondylitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,015
- 主要终点
- Time-Weighted Average Change From Baseline in the Spinal Pain Intensity in Study Part 1: Etoricoxib 90 mg vs. Naproxen
研究概览
简要总结
The purpose of the study is to evaluate the efficacy and tolerability of two doses of etoricoxib compared to naproxen in the treatment of ankylosing spondylitis (AS). The primary objectives are to evaluate the improvement in Spinal Pain Intensity over 6 weeks of treatment with etoricoxib 90 mg or 60 mg compared to naproxen; and to evaluate the improvement in Spinal Pain Intensity over 6 weeks of treatment with etoricoxib 90 mg compared with etoricoxib 60 mg. 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. The primary hypothesis is that the improvement in Spinal Pain Intensity visual analog scale (VAS) as measured by the time-weighted average (TWA) change from baseline over 6 weeks of treatment in Part I for etoricoxib 90 mg or 60 mg once daily is not inferior to naproxen 1000 mg.
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
- •Has a definite diagnosis of Ankylosing Spondylitis (AS) per Modified New York Criteria made at least 6 months prior to screening
- •Has a history of positive therapeutic benefit with non-steroidal anti-inflammatory drugs (NSAIDs) and regular use of NSAIDS for past 30 days
- •Has a score on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 at screening visit that is <77 mm
- •Must demonstrate sufficient "flare" or worsening of AS pain
- •Is in general good health (other than AS)
- •Has had approved non-study antirheumatic therapy that has been at stable dosing AND is not anticipated to undergo a change within the first 6 weeks of the protocol
排除标准
- •Has inflammatory arthritis (eg, rheumatoid arthritis, psoriatic arthritis, crystal-induced arthritis, spondyloarthropathy, diffuse idiopathic skeletal hyperostosis [DISH]), polymyalgia rheumatica, a history of septic arthritis or intra-articular fracture of the study joint, Wilson's disease, hemachromatosis, ochronosis, or primary osteochondromatosis
- •Has acute peripheral articular disease (onset within 4 weeks prior to screening) of an active (painful or swollen) peripheral arthritis
- •Has a history of gastric or biliary surgery, or small intestine surgery that causes clinical malabsorption
- •Has had an active peptic (gastric or duodenal) ulcer or history of inflammatory bowel disease
- •Has undergone coronary artery bypass graft surgery (CABG), angioplasty, or has a cerebrovascular accident or transient ischemic attack within the past 6 months or has active ischemic heart disease, cerebrovascular disease, or peripheral vascular disease
- •Has Class II-IV congestive heart failure
- •Has uncontrolled hypertension
- •Has a history of neoplastic disease, except adequately treated basal cell carcinoma or carcinoma in situ of the cervix, or malignancies that have been successfully treated ≥ 5 years prior to screening
- •Has history of leukemia, lymphoma, malignant melanoma, and myeloproliferative disease
- •Allergy to etoricoxib or naproxen, or history of a significant clinical or laboratory adverse experience associated with etoricoxib or naproxen
- •Has a history or family history of an inherited or acquired bleeding disorder
- •Is considered morbidly obese and demonstrates significant health problems stemming from obesity, which would confound study participation or interpretation of study results
- •Is pregnant, breast-feeding, or expecting to conceive during the study
- •Has a clinical diagnosis of hepatic insufficiency defined as Child-Pugh score ≥ 5
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 in Part I and Part II
干预措施: Part I - etoricoxib 60 mg (Drug)
etoricoxib 60 mg/etoricoxib 60 mg
The etoricoxib 60 mg/etoricoxib 60 mg treatment sequence will receive etoricoxib 60 mg in Part I and Part II
干预措施: Part I - Placebo to naproxen 500 mg (Drug)
etoricoxib 60 mg/etoricoxib 60 mg
The etoricoxib 60 mg/etoricoxib 60 mg treatment sequence will receive etoricoxib 60 mg in Part I and Part II
干预措施: Part II- etoricoxib 60 mg (Drug)
etoricoxib 60 mg/etoricoxib 60 mg
The etoricoxib 60 mg/etoricoxib 60 mg treatment sequence will receive etoricoxib 60 mg in Part I and Part II
干预措施: Part I - Placebo to etoricoxib 90 mg (Drug)
etoricoxib 60 mg/etoricoxib 60 mg
The etoricoxib 60 mg/etoricoxib 60 mg treatment sequence will receive etoricoxib 60 mg in Part I and Part II
干预措施: Part II - Placebo to etoricoxib 90 mg (Drug)
etoricoxib 60 mg/etoricoxib 60 mg
The etoricoxib 60 mg/etoricoxib 60 mg treatment sequence will receive etoricoxib 60 mg in Part I and Part II
干预措施: Part II- Placebo to naproxen 500 mg (Drug)
etoricoxib 60 mg/etoricoxib 90 mg
The etoricoxib 60 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 60 mg in Part I and etoricoxib 90 mg in Part II
干预措施: Part I - etoricoxib 60 mg (Drug)
etoricoxib 60 mg/etoricoxib 90 mg
The etoricoxib 60 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 60 mg in Part I and etoricoxib 90 mg in Part II
干预措施: Part I - Placebo to naproxen 500 mg (Drug)
etoricoxib 60 mg/etoricoxib 90 mg
The etoricoxib 60 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 60 mg in Part I and etoricoxib 90 mg in Part II
干预措施: Part II- etoricoxib 90 mg (Drug)
etoricoxib 60 mg/etoricoxib 90 mg
The etoricoxib 60 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 60 mg in Part I and etoricoxib 90 mg in Part II
干预措施: Part I - Placebo to etoricoxib 90 mg (Drug)
etoricoxib 60 mg/etoricoxib 90 mg
The etoricoxib 60 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 60 mg in Part I and etoricoxib 90 mg in Part II
干预措施: Part II- 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 in Part I and etoricoxib 90 mg in Part II
干预措施: Part II- Placebo to naproxen 500 mg (Drug)
etoricoxib 90 mg/etoricoxib 90 mg
The etoricoxib 90 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 90 mg in Part I and Part II
干预措施: Part I - etoricoxib 90 mg (Drug)
etoricoxib 90 mg/etoricoxib 90 mg
The etoricoxib 90 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 90 mg in Part I and Part II
干预措施: Part I - Placebo to naproxen 500 mg (Drug)
etoricoxib 90 mg/etoricoxib 90 mg
The etoricoxib 90 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 90 mg in Part I and Part II
干预措施: Part II- etoricoxib 90 mg (Drug)
etoricoxib 90 mg/etoricoxib 90 mg
The etoricoxib 90 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 90 mg in Part I and Part II
干预措施: Part I - Placebo to etoricoxib 60 mg (Drug)
etoricoxib 90 mg/etoricoxib 90 mg
The etoricoxib 90 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 90 mg in Part I and Part II
干预措施: Part II- Placebo to etoricoxib 60 mg (Drug)
etoricoxib 90 mg/etoricoxib 90 mg
The etoricoxib 90 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 90 mg in Part I and Part II
干预措施: Part II- Placebo to naproxen 500 mg (Drug)
naproxen 1000 mg/naproxen 1000 mg
The naproxen 1000 mg/naproxen 1000 mg treatment sequence will receive naproxen 1000 mg in Part I and Part II
干预措施: Part I- naproxen 1000 mg (Drug)
naproxen 1000 mg/naproxen 1000 mg
The naproxen 1000 mg/naproxen 1000 mg treatment sequence will receive naproxen 1000 mg in Part I and Part II
干预措施: Part II- naproxen 1000 mg (Drug)
naproxen 1000 mg/naproxen 1000 mg
The naproxen 1000 mg/naproxen 1000 mg treatment sequence will receive naproxen 1000 mg in Part I and Part II
干预措施: Part I - Placebo to etoricoxib 60 mg (Drug)
naproxen 1000 mg/naproxen 1000 mg
The naproxen 1000 mg/naproxen 1000 mg treatment sequence will receive naproxen 1000 mg in Part I and Part II
干预措施: Part I - Placebo to etoricoxib 90 mg (Drug)
naproxen 1000 mg/naproxen 1000 mg
The naproxen 1000 mg/naproxen 1000 mg treatment sequence will receive naproxen 1000 mg in Part I and Part II
干预措施: Part II- Placebo to etoricoxib 60 mg (Drug)
naproxen 1000 mg/naproxen 1000 mg
The naproxen 1000 mg/naproxen 1000 mg treatment sequence will receive naproxen 1000 mg in Part I and Part II
干预措施: Part II - Placebo to etoricoxib 90 mg (Drug)
结局指标
主要结局
Time-Weighted Average Change From Baseline in the Spinal Pain Intensity in Study Part 1: Etoricoxib 90 mg vs. Naproxen
时间窗: Baseline and up to Week 6
Spinal Pain Intensity is measured using a visual analog scale (VAS) from 0-100 mm with a lower value representing a better response. The time-weighted average change is calculated by taking the time between adjacent observations divided by the time from the randomization visit to the last observation in the period of interest, and using it as the weight for computation of the average.
Time-Weighted Average Change From Baseline in the Spinal Pain Intensity in Study Part 1: Etoricoxib 60 mg vs. Naproxen
时间窗: Baseline and up to Week 6
Spinal Pain Intensity is measured using a visual analog scale (VAS) from 0-100 mm with a lower value representing a better response. The time-weighted average change is calculated by taking the time between adjacent observations divided by the time from the randomization visit to the last observation in the period of interest, and using it as the weight for computation of the average.
Number of Participants Discontinuing Study Treatment Due to an Adverse Event
时间窗: Up to 26 weeks
次要结局
- Time-Weighted Average Change From Baseline in the Spinal Pain Intensity in Study Part 1: Etoricoxib 90 mg vs. Etoricoxib 60 mg(Baseline and up to Week 6)
- Average Change From Week 6 in the Spinal Pain Intensity Over Weeks 10 and 12 in Study Part 2: Etoricoxib 60/90 mg vs. Etoricoxib 60mg (Non-responders From Part I)(Week 6 to Week 10 and Week 12)