A 52 WEEK, RANDOMIZED, DOUBLE BLIND, MULTINATIONAL, MULTICENTRE, ACTIVE CONTROLLED, 2-ARM PARALLEL GROUP TRIAL COMPARING CHF 5993 100/6/12.5 µg pMDI (FIXED COMBINATION OF EXTRAFINE BECLOMETASONE DIPROPIONATE PLUS FORMOTEROL FUMARATE PLUS GLYCOPYRRONIUM BROMIDE) TO CHF 1535 100/6 µg pMDI (FIXED COMBINATION OF EXTRAFINE BECLOMETHASONE DIPROPIONATE PLUS FORMOTEROL FUMARATE) IN PATIENTS WITH ASTHMA UNCONTROLLED ON MEDIUM DOSES OF INHALED CORTICOSTEROIDS IN COMBINATION WITH LONG ACTING ß2 AGONISTS
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,155
- 试验地点
- 1
- 主要终点
- Pre-dose FEV1 (Forced Expiratory Volume in the first second)
研究概览
简要总结
Evaluate the superiority of CHF 5993 100/6/12.5 µg Pressurised Metered Dose Inhaler (pMDI) (fixed combination of extrafine beclometasone dipropionate (BDP) plus formoterol fumarate (FF) plus glycopyrronium bromide [GB]) versus CHF 1535 100/6 µg pMDI (fixed combination of extrafine beclometasone dipropionate (BDP) plus formoterol fumarate [FF]), with regard to lung functions parameters and rate of exacerbations as well as safety and health economics outcomes, in adult patients with uncontrolled asthma on medium doses of inhaled corticosteroids in combination with long acting ß2 agonists (LABA).
详细描述
This study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice (GCP) guidelines, and following all other requirements of local laws.
From screening to the end of treatment, vital signs were recorded pre-dose at screening and pre- and postdose at all visits during the treatment period; physical examination was performed at all visits; concomitant medications and adverse events (AEs) were recorded, and asthma exacerbations were assessed at all visits; lung function tests were performed (pre-dose for forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) from screening to end of treatment visits, pre-dose for inspiratory capacity and vital capacity and postdose serial spirometry at all visits during the treatment period).
Patients completed the electronic diary from home twice daily from the time of screening until the end of treatment, to record asthma symptoms, treatment compliance, and use of rescue medication. Patients used the electronic peak flowmeter to record peak expiratory flow twice daily from home from the time of screening until the end of treatment.
Asthma Control Questionnaire© (ACQ)-7 was completed at screening and all visits during the treatment period. The EuroQuality of Life-5-Dimensional-3-Level questionnaire, and health economic and outcome assessments were competed at all visits during the treatment period.
Rescue medication (salbutamol 100 μg per inhalation) was permitted throughout the treatment period when absolutely needed; the maximum allowed dose was 8 inhalations/day (800 μg).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •History of asthma ≥ 1 year and diagnosed before 40 years old
- •Uncontrolled asthma with double therapy only on medium doses of Inhaled CorticoSteroid (ICS) in combination with Long-acting beta2 Agonist (LABA) with ACQ-7 (Asthma Control Questionnaire) ≥1.5
- •Pre-bronchodilator FEV1 <80% of the predicted normal value
- •Positive reversibility test
- •At least 1 documented asthma exacerbation in the previous year
排除标准
- •Pregnant or lactating women
- •Diagnosis of Chronic Obstructive Pulmonary Disease (COPD)
- •Patients with any asthma exacerbation or respiratory tract infection in the 4 weeks prior screening
- •Current or ex-smokers (>= 10 packs year)
- •Any change in dose, schedule or formulation of ICS + LABA combination in the 4 weeks prior screening
研究组 & 干预措施
CHF 1535 100/6 µg
CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF
BDP=Beclometasone Dipropionate bid=Twice daily FF=Formoterol Fumarate
干预措施: CHF 1535 100/6 µg (Drug)
结局指标
主要结局
Pre-dose FEV1 (Forced Expiratory Volume in the first second)
时间窗: at Week 26
Reduction of moderate and severe asthma exacerbations rate
时间窗: Week 0 to Week 52
1_Change From Baseline in Pre-Dose Forced Expiratory Volume in the First Second (FEV1) at Week 26
时间窗: Week 0 (pre-treatment, baseline) to Week 26.
Change from baseline in pre-dose FEV1 was analysed at Week 26 of treatment. FEV1=Forced expiratory volume in the first second
2_Moderate and Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period
时间窗: Week 0 (pre-treatment, baseline) to Week 52.
Asthma exacerbation (events): Moderate AND Severe. Severe: asthma worsening requiring initiation of treatment with systemic corticosteroids for at least 3 days (courses of corticosteroids separated by ≥1 week treated as separate severe exacerbations). Moderate: ≥1 of the following criteria fulfilled and leading to a change in treatment (sustained increase of ≥1 puff of short acting beta 2-agonist \[SABA\] for 2 consecutive days) as shown below: * Nocturnal awakening(s) due to asthma requiring SABA for 2 consecutive nights/increase of ≥0.75 from baseline in daily symptom score on 2 consecutive days; increase from baseline in occasions of SABA use on 2 consecutive days (minimum increase 4 puffs/day); * ≥20% decrease in peak expiratory flow from baseline on at least 2 consecutive mornings/evenings or ≥20% decrease in FEV1 from baseline; * Visit to the ER/trial site for asthma treatment not requiring systemic corticosteroid.
次要结局
- Peak FEV1 (Peak of Forced Expiratory Volume in the first second) within 3 hours post-dose(at Week 26)
- Change from baseline in morning PEF (Peak Expiratory Flow)(Week 0 to Week 26)
- Reduction of severe asthma exacerbations rate(Week 0 to Week 52)
- 3_Change From Baseline in Peak(0-3h) FEV1 at Week 26(Week 0 (pre-treatment, baseline) and Week 26.)
- 4_Change From Baseline in Morning Peak Expiratory Flow (PEF) Over the 26-Week Treatment(Week 0 (pre-treatment, baseline) to Week 26.)
- 5_Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period - Pooled Analysis(The entire treatment period; up to Week 52.)
- 6_Change From Baseline in Peak FEV1 (0-3h) at All Clinical Visits(Week 0 (pre-treatment, baseline) to Week 52.)
- 7_Change From Baseline in Pre-Dose FEV1 at All Clinical Visits(Week 0 (pre-treatment, baseline) to Week 52.)
- 8_FEV1 Response (FEV1 ≥ 100 mL) at Week 26 and Week 52(Week 0 (pre-treatment, baseline) to Week 26 and Week 52.)
- 9_Change From Baseline in FEV1 Area Under the Curve (AUC) (0-3h) Normalised by Time at All Clinical Visits(Week 0 (pre-treatment, baseline) to Week 52.)
- 10_Change From Baseline in the Asthma Control Questionnaire-7 (ACQ-7) Score at All Clinical Visits(Week 0 (pre-treatment, baseline) to Week 52.)
- 11_Asthma Control Questionnaire©-7 Response at Week 26 and Week 52(Week 0 (pre-treatment, baseline) to Week 26 and Week 52)
- 12a_Change From Baseline in Average Morning PEF (L/Min) Over 52 Weeks of Treatment(Week 0 (pre-treatment, baseline) to Week 52.)
- 12b_Change From Baseline in Average Evening PEF (L/Min) Over 26 and 52 Weeks of Treatment(Week 0 (pre-treatment, baseline) to Week 26 and Week 52.)
- 13_Number of Patients at Risk of Moderate or Severe Asthma Exacerbation Over 52 Weeks(Week 0 (pre-treatment, baseline) to Week 52.)
- 14_Number of Patients at Risk of Severe Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02(Week 0 (Baseline) to 52 weeks for both studies in the pooled analysis.)
- 15_Moderate Asthma Exacerbation Rate Over the 52-Week Treatment Period in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 and CCD-055993AB2-02.(Week 0 (pre-treatment, baseline) to Week 52.)
- 16_Number of Patients at Risk of MODERATE Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02(Week 0 (pre-treatment, baseline) to Week 52.)
- 17_Moderate and Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 and CCD-055993AB2-02(Week 0 (pre-treatment, baseline) to Week 52.)
- 18_Number of Patients at Risk of Moderate OR Severe Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02(Week 0 (pre-treatment, baseline) to Week 52.)
- 19_Moderate Asthma Exacerbation Rate Over the 52-Week Treatment Period(Week 0 (pre-treatment, baseline) to Week 52.)
- 20_Number of Patients at Risk of a MODERATE Asthma Exacerbation(Week 0 (pre-treatment, baseline) to Week 52.)
- 21a_Change From Baseline in the Average Use of Rescue Medication Over the 26- and 52-Week Treatment Periods(Week 0 (pre-treatment, baseline) to Week 26 and Week 52.)
- 21b_Change From Baseline in the Average Use of Rescue Medication in Each Inter-Visit Period(Week 0 (pre-treatment, baseline) to Week 52.)
- 22a_Change From Baseline in the Percentage of Rescue Medication-Free Days Over the 26- and 52-Week Treatment Periods(Week 0 (pre-treatment, baseline) to Week 52.)
- 22b_Change From Baseline in the Percentage of Rescue Medication-Free Days in Each Inter-Visit Period Over the Treatment(Week 0 (pre-treatment, baseline) to Week 52.)
- 23a_Change From Baseline in the Average Daily Asthma Symptom Scores Over the 26- and 52-Week Treatment Periods(Week 0 (pre-treatment, baseline) to Week 52.)
- 23b_Change From Baseline in the Average Daily Asthma Symptom Scores in Each Inter-Visit Period(Week 0 (pre-treatment, baseline) to Week 52.)
- 24a_Change From Baseline in the Percentage of Asthma Symptom-Free Days Over the 26- and 52-Week Treatment Periods(Week 0 (pre-treatment, baseline) to Week 52.)
- 24b_Change From Baseline in the Percentage of Asthma Symptom-Free Days in Each Inter-Visit Periods(Week 0 (pre-treatment, baseline) to Week 52.)
- 25a_Change From Baseline in the Percentage of Asthma Control Days Over the 26- and 52-Week Treatment Periods(Week 0 (pre-treatment, baseline) to Week 52.)
- 25b_Change From Baseline in the Percentage of Asthma Control Days in Each Inter-Visit Period(Week 0 (pre-treatment, baseline) to Week 52.)