A Randomized, Double-blind, Repeat Dose Cross-over Study to Assess the Bronchodilator Effects of Once Daily QVM149 Following Morning or Evening Dosing for 14 Days Compared to Placebo in Patients With Asthma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 7
- 主要终点
- FEV1 Standardized Area Under the Curve (AUC 0-24h) After Last Evening Dose of 14-day Treatment Period
研究概览
简要总结
This was a randomized, placebo-controlled, double-blind, six-sequence, three-period cross-over study in asthma patients. The study consisted of a 14-day screening period, followed by a 14-day run-in period, and a treatment epoch which consists of three treatment periods, with a minimum duration of 14 days each followed (for the 2 first treatment periods) by a wash-out period. The duration of each treatment period may be extended up to a duration of 18 days if needed for operational reasons. The third treatment period was followed by a Study Completion evaluation at 1-7 days following the last dose. The treatment periods were separated by wash-out periods of 14 to 21 days duration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind masking.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a documented physician diagnosis of asthma and who additionally meet the following criteria:
- •Patients receiving daily treatment with an inhaled corticosteroid at a low or medium daily dose
- •On a stable regimen for at least 4 weeks prior to screening.
- •Pre-bronchodilator FEV1 ≥ 60 % and < 100% of the predicted normal value for the patient during screening.
- •Patients who demonstrate an increase in FEV1 of ≥ 12 % and ≥ 200 mL after administration of 400 μg salbutamol/360 μg albuterol (or equivalent dose) at Screening. All patients must perform a reversibility test at Screening.
- •At screening, and baseline (day 1 pre-dose time) of the first treatment period, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position and again in the standing position as outlined in the SOM. Sitting and standing vital signs should be within the following ranges:
- •oral body temperature between 35.0-37.5 °C
- •systolic blood pressure, 90-159 mmHg
- •diastolic blood pressure, 50-99 mmHg
- •pulse rate, 40-90 bpm
- •Hypertensive patients must have been on stable antihypertensive therapy for at least 4 weeks prior to screening to be included in the trial.
- •Patients must weigh at least 50 kg at screening to participate in the study, and must have a body mass index (BMI) within the range of 18 to 40 kg/m2.
排除标准
- •Contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the drugs of a similar class
- •Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 1 year of Screening.
- •Patients who have had previous intubation for a severe asthma ttack/exacerbation.
- •Patients with a history of clinically relevant bronchoconstriction upon repeated forced expiratory maneuvers.
- •History of paradoxical bronchospasm in response to inhaled medicines.
- •Patients who during the run-in period prior to randomization require the use of ≥12 puffs / 24 hours of rescue medication for 48 hours (over two consecutive days) or who have a decline in PEF from the reference PEFof ≥ 30% for 6 consecutive scheduled PEF readings
- •Patients who do not maintain regular day/night, waking/sleeping cycles (e.g., night shift workers).
研究组 & 干预措施
Sequence 1
Patients will receive in a sequential order the following interventional treatments: A,B and C.
干预措施: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose) (Drug)
Sequence 1
Patients will receive in a sequential order the following interventional treatments: A,B and C.
干预措施: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose) (Drug)
Sequence 1
Patients will receive in a sequential order the following interventional treatments: A,B and C.
干预措施: Treatment C: Placebo (morning dose) and placebo (evening dose) (Drug)
Sequence 2
Patients will receive in a sequential order the following interventional treatments: B, A and C.
干预措施: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose) (Drug)
Sequence 2
Patients will receive in a sequential order the following interventional treatments: B, A and C.
干预措施: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose) (Drug)
Sequence 2
Patients will receive in a sequential order the following interventional treatments: B, A and C.
干预措施: Treatment C: Placebo (morning dose) and placebo (evening dose) (Drug)
Sequence 3
Patients will receive in a sequential order the following interventional treatments: C, B and A.
干预措施: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose) (Drug)
Sequence 3
Patients will receive in a sequential order the following interventional treatments: C, B and A.
干预措施: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose) (Drug)
Sequence 3
Patients will receive in a sequential order the following interventional treatments: C, B and A.
干预措施: Treatment C: Placebo (morning dose) and placebo (evening dose) (Drug)
Sequence 4
Patients will receive in a sequential order the following interventional treatments : C, A and B.
干预措施: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose) (Drug)
Sequence 4
Patients will receive in a sequential order the following interventional treatments : C, A and B.
干预措施: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose) (Drug)
Sequence 4
Patients will receive in a sequential order the following interventional treatments : C, A and B.
干预措施: Treatment C: Placebo (morning dose) and placebo (evening dose) (Drug)
Sequence 5
Patients will receive in a sequential order the following interventional treatments: A, C and B.
干预措施: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose) (Drug)
Sequence 5
Patients will receive in a sequential order the following interventional treatments: A, C and B.
干预措施: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose) (Drug)
Sequence 5
Patients will receive in a sequential order the following interventional treatments: A, C and B.
干预措施: Treatment C: Placebo (morning dose) and placebo (evening dose) (Drug)
Sequence 6
Patients will receive in a sequential order the following interventional treatments: B, C and A.
干预措施: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose) (Drug)
Sequence 6
Patients will receive in a sequential order the following interventional treatments: B, C and A.
干预措施: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose) (Drug)
Sequence 6
Patients will receive in a sequential order the following interventional treatments: B, C and A.
干预措施: Treatment C: Placebo (morning dose) and placebo (evening dose) (Drug)
结局指标
主要结局
FEV1 Standardized Area Under the Curve (AUC 0-24h) After Last Evening Dose of 14-day Treatment Period
时间窗: At the end of each treatment period day 14 pre-dose to 24 hours post-dose.
Weighted mean forced expiratory volume in 1 second (FEV1) over 24 h (AUC0-24h) following 14 days of treatment with QVM149 dosed in the morning, QVM149 dosed in the evening and placebo.
次要结局
- Trough FEV1 After 24h(At the end of each treatment period day 14 pre-dose to 24 hours post-dose.)
- Peak Expiratory Flow (PEF)(From treatment period start through study completion (up to 19 weeks).)