A Phase 2 Randomized, Double-Blinded, Double-Dummy, Placebo And Active Controlled Two Cohort Two-Way Cross-Over, Multi-Centre Clinical Trial To Examine The Pain Relief Produced By 2 Weeks Of Daily Oral Administration Of A 5-Lipoxygenase (5-Lox) Inhibitor PF-04191834 Alone And In Combination With Naproxen In Patients With Flare-Enriched Osteoarthritis Of The Knee
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 190
- 试验地点
- 1
- 主要终点
- Change From Baseline in Western Ontario & McMaster (WOMAC) Osteoarthritis Index Pain Score at the End of Treatment Period 1
研究概览
简要总结
PF-04191834 works in animal models by inhibiting one of the enzymes, 5-lipoxygenasein which is involved in the pathway that causes inflammation and pain. The purpose of this study is to test how effective, safe and tolerated PF-04191834 is in patients with osteoarthritis of the knee by itself or with naproxen, particularly to test if patients have less pain.
详细描述
This study has been terminated in response to a reported serious adverse event (SAE). The sponsor's assessment of the limited data available at the time of the initial SAE report was that the SAE may alter the potential benefit - risk profile of the study medication.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have a diagnosis of osteoarthritis based on the American College of Rheumatology criteria confirmed by an X-ray
- •Subjects must be willing and able to stop all current pain therapy for the duration of the study
- •Subjects must be willing and able to complete a daily diary
排除标准
- •BMI of >39 kg/m2
- •Known allergy or hypersensitivity to naproxen
- •Any condition or medical history that might interfere with the subject's ability to complete the study visits and assessments
研究组 & 干预措施
PF-04191834 followed by placebo
PF-04191834 600 mg BID dose followed by matched placebo plus naproxen placebo.
干预措施: PF-04191834 (Drug)
PF-04191834 followed by placebo
PF-04191834 600 mg BID dose followed by matched placebo plus naproxen placebo.
干预措施: PF-04191834 placebo (Drug)
PF-04191834 followed by placebo
PF-04191834 600 mg BID dose followed by matched placebo plus naproxen placebo.
干预措施: Naproxen placebo (Drug)
Placebo followed by PF-04191834
Placebo followed by 600 mg BID dose of PF-04191834 plus naproxen placebo.
干预措施: PF-04191834 placebo (Drug)
Placebo followed by PF-04191834
Placebo followed by 600 mg BID dose of PF-04191834 plus naproxen placebo.
干预措施: PF-04191834 (Drug)
Placebo followed by PF-04191834
Placebo followed by 600 mg BID dose of PF-04191834 plus naproxen placebo.
干预措施: Naproxen placebo (Drug)
PF-04191834+Naproxen followed by Naproxen
PF-04191834 600 mg BID + Naproxen 500 mg BID followed by Naproxen 500 mg BID plus PF-04191834 placebo
干预措施: PF-04191834 (Drug)
PF-04191834+Naproxen followed by Naproxen
PF-04191834 600 mg BID + Naproxen 500 mg BID followed by Naproxen 500 mg BID plus PF-04191834 placebo
干预措施: Naproxen (Drug)
PF-04191834+Naproxen followed by Naproxen
PF-04191834 600 mg BID + Naproxen 500 mg BID followed by Naproxen 500 mg BID plus PF-04191834 placebo
干预措施: PF-04191834 placebo (Drug)
Naproxen followed by PF-04191834+Naproxen
Naproxen 500 mg BID followed by PF-04191834 600 mg BID + Naproxen 500 mg BID
干预措施: Naproxen (Drug)
Naproxen followed by PF-04191834+Naproxen
Naproxen 500 mg BID followed by PF-04191834 600 mg BID + Naproxen 500 mg BID
干预措施: PF-04191834 placebo (Drug)
Naproxen followed by PF-04191834+Naproxen
Naproxen 500 mg BID followed by PF-04191834 600 mg BID + Naproxen 500 mg BID
干预措施: PF-04191834 (Drug)
结局指标
主要结局
Change From Baseline in Western Ontario & McMaster (WOMAC) Osteoarthritis Index Pain Score at the End of Treatment Period 1
时间窗: Baseline (Day 1 of Visit 3) and end of treatment Period 1 (Day 15+1 of Visit 5)
The WOMAC Pain subscale, comprised of 5 questions regarding the amount of pain experienced in the index joint, was calculated as the mean of the scores from the 5 individual questions. The WOMAC Pain subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-20, with higher scores indicating higher pain.
Change From Baseline in Western Ontario & McMaster (WOMAC) Osteoarthritis Index Pain Score at the End of Treatment Period 2
时间窗: Baseline (Day 28 of Visit 7) and end of treatment Period 2 (Day 43+1 of Visit 9)
The WOMAC Pain subscale, comprised of 5 questions regarding the amount of pain experienced in the index joint, was calculated as the mean of the scores from the 5 individual questions. The WOMAC Pain subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-20, with higher scores indicating higher pain.
次要结局
- WOMAC Stiffness Domain Score(Baseline (Day 1 of Visit 3 for Period 1 and Day 28 of Visit 7 for Period 2), Day 15+1 of Visit 5 for Period 1, and Day 43+1 of Visit 9 for Period 2)
- WOMAC Physical Function Domain Score(Baseline (Day 1 of Visit 3 for Period 1 and Day 28 of Visit 7 for Period 2), Day 15+1 of Visit 5 for Period 1, and Day 43+1 of Visit 9 for Period 2)
- WOMAC Total Score(Baseline (Day 1 of Visit 3 for Period 1 and Day 28 of Visit 7 for Period 2), Day 15+1 of Visit 5 for Period 1, and Day 43+1 of Visit 9 for Period 2)
- Importance Weighted Total WOMAC Score(Baseline (Day 1 of Visit 3 for Period 1 and Day 28 of Visit 7 for Period 2), Day 15+1 of Visit 5 for Period 1, and Day 43+1 of Visit 9 for Period 2)
- Daily Diary Pain Score During Week 1 of Each Treatment Period(4 days prior to baseline visits (Visits 3 for Period 1 and Vist 8 for Period 2) up to 7 days after baseline visits)
- Daily Diary Pain Score During Week 2 of Each Treatment Period(Over the last 4 days before baseline visits (Visits 3 for Period 1 and Visit 8 for Period 2) and over the last 6 days before Visit 5 for Period 1 and Visit 9 for Period 2)
- Rescue Medication Use(Day -7 (Visit 2) up to 28-day follow-up (Visit 10))
- Plasma Concentration of PF-04191834(Pre-dose and post-dose (1 to 3 hours) on Days 1, 8, 15, 29, 36, and 43)
- Urinary Leukotriene E4 (LTE4) Levels(Day -7 (Visit 2) up to Day 43 (Visit 9 or End of Treatment Period 2))