A 24-week Multi-center, Double-blind, Placebo Controlled Dose-range Finding Study to Investigate the Efficacy and Safety of Oral QBW251 in COPD Patients on Triple Inhaled Therapy (LABA / LAMA / ICS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 974
- 试验地点
- 1
- 主要终点
- Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 12
研究概览
简要总结
This clinical study was designed to support the dose selection for future studies by evaluating efficacy and safety of different QBW251 doses in Chronic obstructive pulmonary disease (COPD) patients with chronic bronchitis and a history of exacerbations, compared to placebo, when added to a triple inhaled therapy of LABA, LAMA and ICS.
详细描述
This study used a 6 treatment arm, parallel-group, randomized, double-blind study design. 974 male and female COPD patients were randomized into the trial. The study consisted of four distinct study periods:
- Screening (Weeks -3 to -2): Participants underwent a screening period of 1 week where were assessed for eligibility and tapered off disallowed medications.
- Run-in (Days -14 to 1): Subsequently, participants entered the run-in period of up to 2 weeks to establish baseline values for symptom assessments, to standardize the COPD background therapy (triple combination LABA/LAMA/ICS), and to complete eligibility assessments.
- Treatment (Day 1 to Week 24): Eligible participants moved into the Day 1 visit where they were stratified according to their smoking status (current or ex-smoker) and severity of airflow limitation (FEV1 ≥ 30% to < 50% and ≥ 50% to < 80%) and then randomized into 1 of 6 treatment arms with a randomization ratio of 2:2:1:1:1:2 (450 mg b.i.d., 300 mg b.i.d., 150 mg b.i.d., 75 mg b.i.d., 25 mg b.i.d., placebo). The treatment period consisted of 24 weeks, during which the participant returned to the site for regular visits (Day 1 - Week 24). QBW251 450 mg arm was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.
- Follow-up (Weeks 25-28): Upon completion of the treatment period, participants were followed up for safety assessments for 30 days.
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, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female COPD patients aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.
- •Current or ex-smokers who have a smoking history of at least 10 pack years.
- •Patients who have been treated with a triple combination of LABA/LAMA/ICS for the last 3 months prior to screening.
- •Patients featuring chronic bronchitis
排除标准
- •Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization, or a respiratory tract infection in the 4 weeks prior to screening, or between screening and randomization.
- •Patients with any documented history of asthma, or with an onset of chronic respiratory symptoms, including a COPD diagnosis, prior to age 40 years.
- •Patients with a body mass index (BMI) of more than 40 kg/m
- •Use of other investigational drugs (approved or unapproved) within 30 days or 5 half-lives prior to screening, or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations.
- •Pregnant or nursing (lactating) women, and women of childbearing potential not willing to use acceptable effective methods of contraception during study participation.
研究组 & 干预措施
QBW251 450 mg
QBW251 was orally administered 450 mg b.i.d for 24 weeks
干预措施: QBW251 (Drug)
QBW251 450 mg
QBW251 was orally administered 450 mg b.i.d for 24 weeks
干预措施: COPD maintenance background therapy (Drug)
QBW251 300 mg
QBW251 was orally administered 300 mg b.i.d for 24 weeks
干预措施: QBW251 (Drug)
QBW251 300 mg
QBW251 was orally administered 300 mg b.i.d for 24 weeks
干预措施: COPD maintenance background therapy (Drug)
QBW251 150 mg
QBW251 was orally administered 150 mg b.i.d for 24 weeks
干预措施: QBW251 (Drug)
QBW251 150 mg
QBW251 was orally administered 150 mg b.i.d for 24 weeks
干预措施: COPD maintenance background therapy (Drug)
QBW251 75 mg
QBW251 was orally administered 75 mg b.i.d for 24 weeks
干预措施: QBW251 (Drug)
QBW251 75 mg
QBW251 was orally administered 75 mg b.i.d for 24 weeks
干预措施: COPD maintenance background therapy (Drug)
QBW251 25 mg
QBW251 was orally administered 25 mg b.i.d for 24 weeks
干预措施: QBW251 (Drug)
QBW251 25 mg
QBW251 was orally administered 25 mg b.i.d for 24 weeks
干预措施: COPD maintenance background therapy (Drug)
Placebo
Placebo was orally administered b.i.d for 24 weeks
干预措施: Placebo (Drug)
Placebo
Placebo was orally administered b.i.d for 24 weeks
干预措施: COPD maintenance background therapy (Drug)
结局指标
主要结局
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 12
时间窗: Baseline and Week 12
The primary efficacy analysis assessed the effect of QBW251 on the absolute change from baseline in trough FEV1 in liters on Week 12. Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline measurement was defined as the baseline visit pre-bronchodilator spirometry assessment. Change from baseline in the FEV1 mean scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in FEV1 + airflow limitation severity + region + time interval + treatment\*time interval interaction + baseline score\*time interval interaction.
次要结局
- Change From Baseline in Forced Expiratory Volume in One Second (FEV1)(Baseline, weeks 4, 8, 16, 20 and 24)
- Change From Baseline in Evaluating Respiratory Symptoms (E-RS); Total Score(Baseline, weeks 12 and 24)
- Change From Baseline in Evaluating Respiratory Symptoms (E-RS); Cough and Sputum Score(Baseline, weeks 12 and 24)
- Number of Participants With a "Better" Change in the Patient Global Impression of Severity (PGI-S) From Baseline(Baseline, weeks 12 and 24)
- Change From Baseline in the Cough and Sputum Assessment Questionnaire (CASA-Q)(Baseline, weeks 12 and 24)
- Change From Baseline in St. George's Respiratory Questionnaire (SGRQ)(Baseline, weeks 12 and 24)
- Minimum Plasma Concentration (Cmin) for QBW251(Pre-dose on Days 15, 29, 57, 85, 113, 141 and 169)
- Maximum Plasma Concentration (Cmax) for QBW251(Days 1, 15 and 169)
- Maximum Plasma Concentration (Cmax) for QBW251 in Serial PK Set(1, 2, 4, 6, and 8 hours post-dose on Days 1 and 15)
- Area Under the Curve From Time 0 to 24 Hours (AUC0-24h) of QBW251 in Serial PK Set(1, 2, 4, 6, and 8 hours post-dose on Days 1 and 15)