Acute Osteoarthritis Experimental Model Study.
A Double Blind, Randomised, Placebo Controlled Methodological Cross-over Study to Investigate the Senstivity of a Novel Study Design and Endpoints to Treatment Effects of Naproxen in Osteoarthritis
研究概览
详细说明
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
-
-
-
Cardiff、英国、CF14 5GJ
- GSK Investigational Site
-
Manchester、英国、M15 6SX
- GSK Investigational Site
-
-
Lancashire
-
Buckshaw Village, Chorley、Lancashire、英国、PR7 7NA
- GSK Investigational Site
-
-
参与标准
资格标准
适合学习的年龄
- 孩子
- 成人
- 年长者
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- A diagnosis of OA of the knee and suitable for the study as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Male or female between 50 to 75 years of age inclusive.
A female subject is eligible to participate if she is of non-childbearing potential defined as:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory].
- Females with menopausal status ( > 12 months of spontaneous amenorrhea) and receiving hormone replacement therapy (HRT) treatment for more than 3 months.
- BMI within the range 15-35 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
Diagnosis
- Have a radiological and clinical diagnosis of OA based upon Arthritis Research Council (ACR) (Appendix 3) criteria affecting at least one knee of a minimum of 3 months in symptom duration prior to screening. An X-ray will be performed at screening if required.
- Have symptomatic OA of at least one knee. The symptoms should be significantly worse in one knee than the other if OA affects both knees.
- When questioned, confirm they experience moderate pain when climbing stairs.
- Be able to walk unaided or with the aid of one stick (2 sticks not allowed)
- A minimum of 4 out 10 on the NRS (numerical rating scales) at screening and/ or a requirement for the use of an analgesic for the pain in the OA knee for most days during the previous three months. In addition, baseline pain must be stable for at least 72 hours prior to day 1 based on patient's assessment or day 1 may be delayed.
- A maximum of 8 out of 10 on the NRS at screening. Enrollement may be delayed if, in the opinion of the investigator, the severity of pain represents an isolated incident.
- In good general health with (in the opinion of the investigator) no clinically significant and relevant abnormalities of medical history or physical examination and suitable for treatment with both naproxen and paracetamol.
Exclusion Criteria:
General
- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. However, a positive drug screen will not automatically exclude a subject if there is a valid explanation for the positive result other than drug abuse e.g. poppy seeds.
History of regular alcohol consumption within 6 months of the study defined as:
• An average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
- Intolerance of paracetamol or not response to Non Steriodal Anti Inflammatory Drugs (NSAID) therapy.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Use of anticoagulants (warfarin, heparin) or anti-platelet aggregation agents (excluding low-dose aspirin) or a condition associated with decreased haemostasis.
- Use of prescription or non-prescription drugs within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. Please also see OA exclusion criteria 10.
- Subject with a known allergy to or judged by the investigator not to be a suitable candidate for naproxen or paracetamol therapy based on medical history, concomitant medications, and concurrent systemic disease as described in the product labelling
- History or presence of gastro-intestinal, hepatic or renal disease or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. In particular dyspepsia, peptic ulceration, gastrointestinal bleeding, ulcerative colitis or Crohn´s disease
- Presence of anaemia.
- Subjects who have asthma, have received anti-asthmatic medication within the last 5 years, have a history of NSAID-sensitive asthma or who have ever required hospital admission due to asthma.
- Presence of cardiac heart failure NYHA > 1.
- Presence of hypertension (BP systolic > 150 mmHg, diastolic > 90 mmHg) not adequately controlled by antihypertensive treatment.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Unwillingness or inability to follow the procedures outlined in the protocol including being able to undertake the walking as defined in the protocol.
- Inability or unwillingness to comply with study restrictions.
Exclusion criteria related to OA
- Secondary causes of arthritis of the knee including septic arthritis, inflammatory joint disease, articular fracture, major dysplasias or congenital abnormality, ochronosis, acromegaly, hemochromatosis, Wilson's disease, and primary osteochondromatosis.
- Had lower extremity surgery (including arthroscopy) within 6 months prior to screening or scheduled for surgery of any kind during the study period
- Significant prior injury to the index knee within 12 months prior to screening.
- Disease of the spine or other lower extremity joints of sufficient degree to affect the index knee.
- Any other musculoskeletal or arthritic condition that may affect the interpretation of clinical efficacy and/or safety data or otherwise contraindicates participation in this clinical study (i.e., currently symptomatic fractures or any concurrent rheumatic disease such as but not limited to fibromyalgia, rheumatoid arthritis, and Reiter's syndrome are excluded).
Corticosteroid use prior to baseline as follows:
- Intra-articular injection of steroids to the index knee within the previous 3 months
- Intra-articular steroid injections into any site other than the index knee within the previous 1 month
- Intra-muscular corticosteroid injections within the previous 3 months
- Oral corticosteroids within the previous 1 month
- Received hyaluronan injections into index knee within the previous six months prior to baseline.
- Initiation of or change to an established physiotherapy program within 2 weeks prior to baseline or during the study period. An established physiotherapy program may be continued throughout the study period if unchanged in frequency and intensity.
- Recent start or change in dose regimen ( 3 months prior to baseline) of any OA specific therapies (i.e., nutraceutical products) including but not limited to chondroitin or keratin sulfate, s-adenosyl methionine (SAMe) and glucosamine preparations.
- Use of opioid analgesics other than codeine containing preparations.
学习计划
研究是如何设计的?
设计细节
- 分配:随机化
- 介入模型:交叉作业
- 屏蔽:双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
安慰剂比较:安慰剂
|
安慰剂
|
实验性的:积极的
|
Capsule
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Change from baseline in the time to ascend and descend 11 stairs
大体时间:Screening, Day 1, Days 8,10,15,17,22,24
|
Screening, Day 1, Days 8,10,15,17,22,24
|
次要结果测量
结果测量 |
大体时间 |
---|---|
Pain intensity difference as measured on numerical rating scales (NRS) after ascending and descending 11 stairs.
大体时间:Screening, Day 1,Days 8,10,15,17,22,24
|
Screening, Day 1,Days 8,10,15,17,22,24
|
Change from baseline in the time to walk 20, 40 and 100m.
大体时间:Screening, Day 1, Days 8,10,15,17,22,24
|
Screening, Day 1, Days 8,10,15,17,22,24
|
Pain intensity difference as measured on a numerical rating scales (NRS) after: 100m walk
大体时间:Screening, Day 1, Days 8,10,15,17,22,24
|
Screening, Day 1, Days 8,10,15,17,22,24
|
Pain intensity difference as measured on a numerical rating scales (NRS) after: resting
大体时间:Screening,Day 1, Days 2 to 7, 9, 11 to 14, 16, 18 to 21, 23, Days 8,10,15,17,22,24
|
Screening,Day 1, Days 2 to 7, 9, 11 to 14, 16, 18 to 21, 23, Days 8,10,15,17,22,24
|
Change from baseline in WOMAC scores
大体时间:Day 1, Days 8,10,15,17,22,24
|
Day 1, Days 8,10,15,17,22,24
|
Patient Global Impression of Change (PGIC).
大体时间:Days 8,10,15,17,22,24
|
Days 8,10,15,17,22,24
|
合作者和调查者
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
安慰剂的临床试验
-
City of Hope Medical CenterNational Cancer Institute (NCI)主动,不招人造血和淋巴细胞肿瘤 | 骨髓纤维化 | 慢性淋巴细胞白血病 | 缓解期成人急性髓性白血病 | 骨髓增生异常综合症 | 缓解期成人急性淋巴细胞白血病 | 骨髓增殖性肿瘤 | 慢性期慢性粒细胞白血病,BCR-ABL1 阳性 | 成人淋巴母细胞淋巴瘤 | 加速期慢性粒细胞白血病,BCR-ABL1 阳性 | HLA-A*0201 阳性细胞存在 | 巨细胞病毒感染 | 成人霍奇金淋巴瘤 | 成人非霍奇金淋巴瘤美国
-
Mila (bMotion Technologies)完全的
-
Universidad Autonoma de MadridCentro Universitario La Salle完全的