A 2-Year, Dose Range-Finding, Adaptive-Design Study of the Effects of SCH 527123 in Subjects With Moderate to Severe COPD
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 616
- 主要终点
- Change From Baseline in Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Period 1)
研究概览
简要总结
Neutrophils are thought to play an important role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Navarixin (SCH 527123, MK-7123) is an antagonist of the cysteine-X-cysteine chemokine receptor 2 (CXCR2) and is thought to reduce neutrophil migration to the diseased lung. It is theorized that reducing neutrophil migration to the diseased lung will improve a participant's symptoms and the natural history of the disease.
The study will consist of a 2-week screening period followed by a 2-year (104-week) double-blind treatment period. The 2-year Treatment Period will be made up of two phases: a 26-week (6-month) dose range-finding phase with 3 active arms and 1 placebo arm (Period 1), followed by a 78-week (18-month) long-term safety and efficacy phase (Period 2). Participants participating in the original 6-month study (Period 1) may elect not to continue into the 18-month extension study (Period 2).
Hypothesis: navarixin, 50 mg, or the highest remaining dose if the 50-mg dose is discontinued, is superior to placebo with respect to improving airflow.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 41 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of COPD for at least 2 years based on American Thoracic Society/European Respiratory Society (ATS/ERS) current guidelines or symptoms consistent with COPD for at least 2 years.
- •>40 to <=75 years of age, of either sex, and of any race.
- •No exacerbation or respiratory infection in the past 6 weeks.
- •Smoker or ex-smoker with more than 10 pack-year history.
排除标准
- •Diagnosis of asthma or other clinically relevant lung disease (other than COPD), i.e., sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis, or lung cancer.
- •Significant X-ray findings.
- •Use of supplemental oxygen for >12 hours/day.
研究组 & 干预措施
Navarixin 30 mg
Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years
干预措施: Placebo (Drug)
Navarixin 50 mg
Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years
干预措施: Rescue medication (Drug)
Placebo
Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
干预措施: Placebo (Drug)
Navarixin 10 mg
Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally once daily (QD) for up to 2 years
干预措施: Placebo (Drug)
Navarixin 10 mg
Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally once daily (QD) for up to 2 years
干预措施: Rescue medication (Drug)
Navarixin 30 mg
Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years
干预措施: Rescue medication (Drug)
Placebo
Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
干预措施: Rescue medication (Drug)
Navarixin 30 mg
Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years
干预措施: Navarixin (Drug)
Navarixin 10 mg
Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally once daily (QD) for up to 2 years
干预措施: Navarixin (Drug)
Navarixin 50 mg
Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years
干预措施: Navarixin (Drug)
结局指标
主要结局
Change From Baseline in Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Period 1)
时间窗: Baseline and Week 26
FEV1, as measured in liters by spirometry, is the amount of air expired in 1 second. Participants were assessed for post-bronchodilator FEV1 30 minutes after bronchodilator administration (4 puffs of albuterol/salbutamol or equivalent separated by 30-second intervals) (reversibility test) at Baseline and Week 26.
Percentage of Participants With an Adverse Event (AE) Related to a Blood Absolute Neutrophil Count (ANC) of Less Than 1.5x10^9 Cells/L
时间窗: Up to 104 weeks
The percentage of participants who experienced an AE related to an ANC of less than 1.5x10\^9 cells/L at one or more visits during the first 26 weeks, the first 52 weeks and the first 104 weeks was to be calculated.
次要结局
- Induced Sputum Absolute Neutrophil Counts(Baseline, Week 26, Week 52, Week 104)
- Change From Baseline in Post-bronchodilator FEV1 (Period 2)(Baseline and Week 52, Week 104)
- Total Exacerbations of Chronic Pulmonary Disease Tool-Patient-Recorded Outcome (EXACT-PRO) Questionnaire Score(At 26, 52 and 104 weeks)
- Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)(Baseline and Week 26, Week 52, Week 104)
- Change From Baseline in Pre-bronchodilator FEV1(Baseline and Week 26, Week 52, Week 104)
- Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score(Baseline and Week 26, Week 52, Week 104)
- Plasma Inflammatory Biomarker Levels: Fibrinogen(Baseline, Week 26, Week 52, Week 104)
- Percentage of Participants With a Moderate to Severe COPD Exacerbation(Up to 26, 52 and 104 weeks)
- Change From Baseline in Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity (FEF25%-75%) Test(Baseline and Week 26, Week 52, Week 104)
- Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)(Baseline and Week 26, Week 52, Week 104)
- Change From Baseline in Functional Residual Capacity (FRC)(Baseline and Week 26, Week 52, Week 104)
- Change From Baseline in Morning Peak Expiratory Flow (PEF)(Baseline and Week 26, Week 52, Week 104)
- Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)(Baseline, Week 26, Week 52, Week 104)
- Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation(Up to 26 , 52 and 104 weeks)
- Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score(Baseline and Week 26, Week 52, Week 104)
- Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)(Baseline, Week 26, Week 52, Week 104)
- Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)(Baseline, Week 26, Week 52, Week 104)
- Change From Baseline in Pre- and Post-6-Minute-Walk-Test Borg Scale Score(Baseline and Week 26, Week 52, Week 104)
- Percentage of Participants Who Experienced an AE Related to Respiratory Infection(Up to 26 , 52 and 104 weeks)
- Change From Baseline in Total Lung Capacity (TLC)(Baseline and Week 26, Week 52, Week 104)
- Change From Baseline in Inspiratory Capacity (IC)(Baseline and Week 26, Week 52, Week 104)
- Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)(Baseline, Week 26, Week 52, Week 104)
- Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)(Baseline, Week 26, Week 52, Week 104)
- Percentage of Participants Who Experienced an AE Related to Any Type of Infection(Up to 26 , 52 and 104 weeks)
- Change From Baseline in Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Index Score(Baseline and Week 26, Week 52, Week 104)
- Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase(Baseline, Week 26, Week 52, Week 104)
- Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)(Baseline, Week 26, Week 52, Week 104)
- Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase(Baseline, Week 26, Week 52, Week 104)
- Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)(Baseline, Week 26, Week 52, Week 104)
- Change From Baseline in Percent of Arterial Oxygen Saturation Measured by Pulse Oximetry Before and After the 6-Minute Walk Test(Baseline and Week 26, Week 52, Week 104)