An Open-label, Prospective, Three Arm, Parallel Group, Randomized, Multicentric Phase-III Clinical Study to Evaluate the Efficacy and Safety between monotherapy of oral Roflumilast 0.5mg Tablet and combination therapy of Roflumilast 0.5 mg tablet plus Salmeterol 25mcg oral inhaler and combination therapy of Roflumilast 0.5 mg tablet plus Tiotropium 9mcg oral inhaler in adult patients with Chronic Obstructive Pulmonary Disease.
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 300
- 试验地点
- 5
- 主要终点
- 1)Mean change in the pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) between the treatment arms
研究概览
简要总结
Roflumilast is a drug which acts as a selective, long-actinginhibitor of the enzyme PDE-4. It has anti-inflammatory effects and is underdevelopment as an orally administered drug for the treatment of inflammatoryconditions of the lungs such as asthma, and chronic obstructive pulmonarydisease (COPD).[11,12,13,14]While Roflumilast was found to be effective in clinical trials, it producedseveral dose-limiting side effects including nausea, diarrhea and headache, anddevelopment is continuing in an attempt to minimize the incidence of sideeffects while retaining clinical efficacy.[15]
Roflumilast especially alter the underlying inflammation ofCOPD or disease progression. The anti-inflammatory activity ofthe selective PDE4 inhibitor Roflumilast has been proven in vitro and inseveral animal models of inflammation and includes, among other activities,inhibition of the synthesis of leukotriene B4 and reactive oxygen species in neutrophils,as well as partial inhibition of tumor necrosis factor α (TNF- α) from mononuclearcells. The therapeutic utility of previous PDE4 inhibitors in development waslimited due to intolerability and an inadequate demonstration of efficacy inCOPD.
In contrast, clinical studies have demonstrated higherpharmacologic activity and better tolerability of Roflumilast as compared toearlier PDE4-inhibitors in development. Therefore, Roflumilast has beendeveloped as an innovative once-daily oral treatment for COPD, targeting theinflammatory processes that are relevant to the disease. Roflumilast isexpected to provide more targeted anti-inflammatory activity in COPD than corticosteroids,which do not suppress a predominantly neutrophilic inflammatory response inthis patient population. (Barnes, 2003)
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 35.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or female patients aged 35-65 years.
- •Patients willing and able to participate in all aspects of the core study, including use of oral medication, completion of subjective evaluations, attending scheduled clinic visits and compliance with protocol requirements as evidenced by providing written informed consent 3)COPD patients having at least one documented moderate or severe exacerbation within one year prior to baseline visit.
- •FEV1 ≤ 50% of predicted.
- •FEV1/FVC ratio ≤ 70%.
- •Patients already on therapy for COPD with beta2 adrenergic receptor agonists / muscarinic receptor antagonists / Xanthine class of drugs.
- •Presence of respiratory symptoms of COPD including dyspnea, cough and sputum production.
- •Current smokers or patients with a history of smoking.
- •For women of child-bearing potential: women is not pregnant (and has to undergo urine pregnancy test at the time of screening which must be negative) and not nursing, and is practicing an acceptable method of birth control.
排除标准
- •Inability to adequately perform spirometry.
- •COPD exacerbation indicated by a treatment with systemic corticosteroids and/or antibiotics not stopped within 4 weeks prior to screening visit and remains uncontrolled in between the treatment periods.
- •Diagnosis of asthma and/or other relevant lung disease.
- •Suffering from any concomitant disease that might interfere with study procedures or evaluation.
- •Lower respiratory tract infection not resolved 4 weeks prior to the screening visit.
- •Known clinically significant cardiopulmonary abnormalities (diagnosed clinically or documented by X-ray or ECG) and are not related to COPD and that require further evaluation.
- •Known case of HIV and/or patient currently on cytotoxic drugs.
- •Hepatitis and/or liver insufficiency (SGOT and/or SGPT ≥ 5 times the upper limit of the normal reference range) 9)Renal insufficiency (S.
- •Creatinine ≥ 5 times the upper limit of the normal reference range) 10)Known or suspected hypersensitivity to the study drug or its components.
- •Known or suspected hypersensitivity to milk-proteins.
- •Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial.
- •History of, or known current problem with, substance abuse, or any medical, psychological, and/or social condition that may interfere with the patients participation in the study, or with evaluation of the study results.
- •Mentally incompetent or unable or unwilling to provide informed consent or comply with study procedures.
- •Have any condition or situation that, in the opinion of the investigator, would prevent proper evaluation of the safety of the study drug according to the study protocol (e.g., poorly compliant subject).
结局指标
主要结局
1)Mean change in the pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) between the treatment arms
时间窗: From baseline visit to end of the therapy i.e. Week 24±2 days
2)Mean change in the post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) between the treatment arms
时间窗: From baseline visit to end of the therapy i.e. Week 24±2 days
次要结局
- Mean change in the reduction of COPD exacerbations between the treatment arms(From baseline visit to each post randomization visit)
- Changes in the mean FEV1/FVC ratio between the treatment arms(From baseline to end of the therapy i.e. Week 24±2 days)
- Percentage of the subjects reporting AE and/or ADR.
- Assessment of clinical laboratory parameters(At visit 1 (baseline) and visit 7 (end of therapy))
- General examination and assessment of vital signs.(At every visit)