A 2-Week Double-Blind, Placebo-Controlled, Parallel Group Study Comparing the Anti-Inflammatory Effects of Low, Medium, and High Dose Mometasone Furoate/Formoterol Fumarate MDI Formulation and Medium Dose Mometasone Furoate DPI and MDI Formulations in Adults and Adolescents With Persistent Allergic Asthma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 93
- 主要终点
- Mean Percent Change From Baseline to Day 14 in Exhaled Nitric Oxide (eNO) Parts Per Billion (Ppb)
研究概览
简要总结
This is a 2-week double-blind, placebo-controlled, parallel group study comparing the anti-inflammatory effects of low, medium, and high dose mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) formulation and medium dose mometasone furoate (MF) dry powder inhaler (DPI) and MDI formulations in adults and adolescents with persistent allergic asthma.
详细描述
This is a 2-week double-blind, placebo-controlled, parallel group study comparing the anti-inflammatory effects of low, medium, and high dose mometasone furoate/formoterol fumarate MDI formulation and medium dose mometasone furoate (MF) DPI and MDI formulations in adults and adolescents with persistent allergic asthma. An open-label run in period is to be followed by a double-blind treatment period.
A total of 90 subjects (15 per treatment) will be enrolled to ensure 12 subjects per treatment at the Day 14 evaluation, accounting for a 20% drop-out rate. A sample size of 12 subjects per treatment is required to detect a treatment difference of 28% in percent change of eNO at Day 14, assuming a pooled standard deviation of 20% with a power of 90%. These estimates are based on examination of eNO levels in asthmatic vs healthy subjects in an article written by S.A. Kharitonov et. al, 2003.
Subjects will be randomized to one of six treatment groups (MF/F MDI 100/10 mcg BID, MF/F MDI 200/10 mcg BID, MF/F MDI 400/10 mcg BID, MF DPI 200 mcg BID, MF MDI 200 mcg BID, or Placebo MDI BID) according to an Schering-Plough Research Institute (SPRI) computer-generated randomization schedule. Randomization will be performed in appropriately sized blocks using random numbers generated by statistical analysis software (SAS).
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To document asthma diagnosis, historical reversibility defined as an increase in absolute forced expiratory volume (in liters) in 1 second (FEV1) of >= 12% and >= 200 mL must have been performed within 12 months of Screening. For subjects without historical reversibility, one of the following methods can be used at the Screening Visit or at any time before the Baseline Visit:
- •Demonstration of an increase in absolute FEV1 of at least 12% and a volume increase of at least 200 mL within 15-20 minutes after administration of 4 inhalations of albuterol/salbutamol (total dose 360 to 400 mcg) or of nebulized short-acting beta agonist (SABA) (2.5 mg), if confirmed as standard office practice, OR
- •Demonstration of a peak expiratory flow (PEF) variability of more than 20% expressed as a percentage of the mean highest and lowest morning prebronchodilator PEF over at least 1 week, OR
- •Demonstration of a diurnal variation PEF of more than 20% based on the difference between the prebronchodilator (before taking albuterol/salbutamol) morning value and the postbronchodilator value (after taking albuterol/salbutamol) from the evening before, expressed as a percentage of the mean daily PEF value on any day during the open-label Run-in Period. {The calculation formula: Diurnal PEF Variation = Absolute [(highest of 3 readings, PM Post-bronchodilator (BD) PEF from prior evening) - (highest of 3 readings, AM Pre-BD from morning value)]/[(highest PM Post-BD + highest AM Pre-BD)/2] * 100}
- •At Screening and Baseline Visits, a subject must have persistent allergic asthma with an FEV1 >65% predicted.
- •A subject must be allergic to at least one common allergen (grasses, trees, weeds, house dust mites, molds, dog and cat) as demonstrated by clinical symptoms when exposed to the allergen(s), and by skin prick testing or a radioallergosorbent (RAST) class >1 (excluding modified RAST procedure [mRAST]) within 2 years of inclusion in the study.
- •If, based upon the medical judgment of the investigator, there is no inherent harm in changing the subject's current asthma therapy, the subject and/or parent/guardian) must agree to discontinue prescribed inhaled corticosteroid (ICS), anticholinergics, leukotriene receptor inhibitors, and long-acting beta-2 agonists at the Screening Visit as per required washouts, and be transferred to treatment with SABA for relief for 2 weeks before the Baseline/Randomization Visit.
- •Clinical laboratory tests (complete blood count, blood chemistries, and urinalysis) conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator.
- •An electrocardiogram (ECG) performed at the Screening Visit or within 30 days prior to Screening Visit must be clinically acceptable to the investigator and have a QTc interval <440 milliseconds for males and <450 msec for females.
- •At Screening or any time prior to Baseline, a subject must have an eNO level of >30 parts per billion (ppb) at a flow rate of 50 mL/second.
- •At Screening or any time before Baseline, a subject must have a sputum eosinophil count >3% of total cell count.
- •Willingness to give written informed consent and ability to adhere to dose and visit schedules. A subject 12 to 17 years of age must also provide written assent.
- •A nonpregnant female subject of childbearing potential (with a negative serum pregnancy test at Screening) must use a medically acceptable, adequate form of birth control. If not currently sexually active she must agree to use a double-barrier method if she becomes sexually active during the study.
排除标准
- •Use of systemic glucocorticosteroids within 3 months before Screening.
- •Upper or lower respiratory tract infection within 4 weeks before Screening.
- •Decrease in absolute FEV1 >20% between Screening and Baseline Visits.
- •Requirement for > 8 inhalations per day of SABA MDI, or 2 or more nebulized treatments of 2.5 mg SABA, on any 2 consecutive days between the Screening and Baseline Visits.
- •A decrease in AM or PM PEF below the Run-in Period stability limit on any 2 consecutive days before Baseline. At Visit 1, the Run-in Period stability limit for PEF will be established based on the subject's personal best. If the subject does not have a historical personal best, the historical PEF measurement will be the PEF predicted based on the subject's sex, age, and height. PEF value to be multiplied by 0.70 to determine stability limit.
- •A clinical asthma exacerbation defined as a clinical deterioration of asthma that results in emergency treatment, hospitalization for asthma, or treatment with additional, excluded asthma medication (including oral or other systemic corticosteroids but allowing SABA), as per investigator, between Screening and Baseline Visits.
- •Inability to induce sputum after 1 or 2 trys.
研究组 & 干预措施
MF/F MDI 100/10 mcg
干预措施: mometasone furoate/formoterol 100/10 mcg (Drug)
MF/F MDI 200/10 mcg
干预措施: mometasone furoate/formoterol 200/10 mcg (Drug)
MF/F MDI 400/10 mcg
干预措施: mometasone furoate/formoterol 400/10 mcg (Drug)
MF DPI 200 mcg
干预措施: MF DPI 200 mcg (Drug)
MF MDI 200 mcg
干预措施: MF MDI 200 mcg (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Percent Change From Baseline to Day 14 in Exhaled Nitric Oxide (eNO) Parts Per Billion (Ppb)
时间窗: Baseline to Day 14
次要结局
- Mean Percent Change From Baseline to Day 7 in eNO Ppb(Baseline to Day 7)
- Mean Percent Change From Baseline to Day 14 in Sputum Eosinophil Count (Percentage)(Baseline to Day 14)
- Change From Baseline in AM Total Asthma Symptom Score at Days 2-15(Baseline and Days 2-15)
- Change From Baseline in AM Peak Expiratory Flow (PEF) at Days 2-15(Baseline and Days 2-15)
- Change From Baseline in PM PEF at Days 1-15(Baseline and Days 1-15)
- Mean Change From Baseline to Day 15 of Mannitol Challenge(Baseline to Day 15)
- Change From Baseline in PM Total Asthma Symptom Score at Days 1-15(Baseline and Days 1-15)