A 12-Week, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Fluticasone Propionate Multidose Dry Powder Inhaler Compared With Fluticasone/Salmeterol Multidose Dry Powder Inhaler in Adolescent and Adult Patients With Persistent Asthma Symptomatic Despite Inhaled Corticosteroid Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 882
- 试验地点
- 154
- 主要终点
- Standardized Baseline-Adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Effect Curve From Time Zero to 12 Hours PostDose (FEV1 AUEC0-12) at Week 12
研究概览
简要总结
The primary objective of this study was to evaluate the efficacy of fluticasone propionate (Fp) multidose dry powder inhaler (MDPI) and fluticasone propionate/salmeterol xinafoate (FS) MDPI when administered over 12 weeks in patients 12 years of age and older with persistent asthma.
详细描述
Study drug and placebo were supplied in Teva multidose dry powder inhaler (MDPI) devices and provided for participants to use at home. Participants performed spirometry at every visit. Each participant was given a diary at each visit for use until the next visit. Rescue medication (albuterol/salbutamol) was dispensed at each visit, if needed, as determined by the investigational center personnel.
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
- •Best pre-bronchodilator forced expiratory volume in 1 second (FEV1) of 40 to 85% of their predicted normal value.
- •Current Asthma Therapy: Patients must have a short-acting β2-agonist (for rescue use) for a minimum of 8 weeks before the Screening Visit (SV) and a qualifying dose of an inhaled corticosteroid (ICS). The ICS may be either as ICS monotherapy or as an ICS/long-acting beta agonist (LABA) combination. The ICS component of the patient's asthma therapy should be stable for a minimum of 1 month before providing consent.
- •Reversibility of Disease: Patients must have at least 15% reversibility (all patients) and at least a 200 mL increase from baseline FEV1 (patients age 18 and older) within 30 minutes after 2 to 4 inhalations of albuterol/salbutamol at the SV. Note: Patients who do not qualify for the study due to failure to meet reversibility will be permitted to perform a retest once within 7 days.
- •Patients must provide written informed consent/assent.. For minor patients (ages 12 to 17 years, or as applicable per local regulations), the written ICF must be signed and dated by the parent/legal guardian and the written assent form must be signed and dated by the patient (if applicable). Note: Age requirements are as specified by local regulations.
- •Outpatient >= 12 years of age on the date of consent/assent. In countries where the local regulations permit enrollment of adult patients only, patients must be 18 years of age and older.
- •Asthma diagnosis: The patient has a diagnosis of asthma as defined by the National Institute of Health (NIH). The asthma diagnosis has been present for a minimum of 3 months and has been stable (defined as no exacerbations and no changes in asthma medication) for at least 30 days.
- •The patient is able to perform acceptable and repeatable spirometry.
- •The patient is able to perform peak expiratory flow (PEF) with a handheld peak flow meter.
- •The patient is able to use a metered dose inhaler (MDI) device without a spacer device and a multidose dry powder inhaler (MDPI) device.
- •The patient is able to withhold (as judged by the investigator) his or her regimen of ICS or study drug, and rescue medication for at least 6 hours before the screening visit (SV) and before all treatment visits.
- •The patient/parent/legal guardian/caregiver is capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the investigator, capable of giving informed consent/assent and being compliant with all study requirements.
- •SABAs: All patients must be able to replace their current SABA with albuterol/salbutamol HFA MDI inhalation aerosol for the duration of the study.
- •Female patients may not be pregnant, breastfeeding, or attempting to become pregnant.
- •other criteria may apply, please contact the investigator for more information
排除标准
- •A history of a life-threatening asthma exacerbation (an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, or hypoxic seizures).
- •The patient is pregnant or lactating, or plans to become pregnant during the study period or for 30 days after the study.
- •The patient has participated as a randomized patient in any investigational drug study within 30 days of the SV.
- •The patient has previously participated as a randomized patient in a study of Fp MDPI or FS MDPI.
- •The patient has a known hypersensitivity to any corticosteroid, salmeterol, or any of the excipients in the study drug or rescue medication formulation (ie, lactose).
- •The patient has been treated with any known strong cytochrome P450 (CYP) 3A4 inhibitors (eg, azole antifungals, ritonavir, or clarithromycin) within 30 days before the SV.
- •The patient has been treated with any of the prohibited medications during the prescribed (per protocol) washout periods before the SV.
- •The patient currently smokes or has a smoking history of 10 pack years or more (a pack year is defined as smoking 1 pack of cigarettes/day for 1 year). The patient must not have used tobacco products within the past year (eg, cigarettes, cigars, chewing tobacco, or pipe tobacco).
- •The patient has a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that has not resolved at least 2 weeks before the SV.
- •The patient has a history of alcohol or drug abuse within 2 years preceding the SV.
- •The patient has had an asthma exacerbation requiring systemic corticosteroids within 30 days before the SV, or has had any hospitalization for asthma within 2 months before the SV.
- •Initiation or dose escalation of immunotherapy (administered by any route) is planned during the study period. However, patients on stable immunotherapy may be considered for inclusion.
- •The patient has used immunosuppressive medications within 4 weeks before the SV.
- •The patient is unable to tolerate or unwilling to comply with the appropriate washout periods and withholding of all applicable medications.
- •The patient has untreated oral candidiasis at the SV. Patients with clinical visual evidence of oral candidiasis who agree to receive treatment and comply with appropriate medical monitoring may enter the study.
- •The patient has a history of a positive test for human immunodeficiency virus (HIV), active hepatitis B virus, or hepatitis C infection.
- •The patient is either an employee or an immediate relative of an employee of the clinical investigational center.
- •A member of the patient's household is participating in the study at the same time. However, after the enrolled patient completes or discontinues participation in the study, another patient from the same household may be screened.
- •The patient has a disease/condition that in the medical judgment of the investigator would put the safety of the patient at risk through participation or that could affect the efficacy or safety analysis if the disease/condition worsened during the study.
- •other criteria may apply, please contact the investigator for more information
研究组 & 干预措施
FS MDPI 200 / 12.5 mcg
Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.
干预措施: FS MDPI (Drug)
FS MDPI 200 / 12.5 mcg
Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.
干预措施: Albuterol/salmeterol HFA MDI (Drug)
FS MDPI 100 / 12.5 mcg
Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.
干预措施: FS MDPI (Drug)
FS MDPI 100 / 12.5 mcg
Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.
干预措施: Albuterol/salmeterol HFA MDI (Drug)
Fp MDPI 200 mcg
Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.
干预措施: Fp MDPI (Drug)
Fp MDPI 200 mcg
Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.
干预措施: Albuterol/salmeterol HFA MDI (Drug)
Fp MDPI 100 mcg
Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.
干预措施: Fp MDPI (Drug)
Fp MDPI 100 mcg
Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.
干预措施: Albuterol/salmeterol HFA MDI (Drug)
Placebo MDPI
Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.
干预措施: Placebo MDPI (Drug)
Placebo MDPI
Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.
干预措施: Albuterol/salmeterol HFA MDI (Drug)
结局指标
主要结局
Standardized Baseline-Adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Effect Curve From Time Zero to 12 Hours PostDose (FEV1 AUEC0-12) at Week 12
时间窗: Day 1 (predose, baseline), Week 12 and was performed at the following times relative to the administration of study drug (±5 minutes): 15 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, and 12 hours
A subset of patients performed postdose serial spirometry. Data from these assessments were used to analyze the primary endpoint of baseline-adjusted FEV1 AUEC0-12h at week 12 using the trapezoidal rule based on actual time of measurement. It was standardized by dividing it by the number of hours between the start time of dose administration and the end time of the last nonmissing FEV1 measurement. The baseline FEV1 was the average of the 2 predose FEV1 measurements (30 and 10 minutes predose). If 1 of these was missing, the nonmissing value was used; if both were missing, baseline was treated as missing. Baseline-adjusted FEV1 was calculated as postdose FEV1 after subtracting the baseline FEV1 value.
Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
时间窗: Day 1 (predose, baseline), Week 12
Trough FEV1 is a morning spirometry taken predose and pre-rescue bronchodilator. The baseline for predose FEV1 was defined as the average of the 30-minute and 10-minute predose measurements obtained at the randomization visit (Day 1).
次要结局
- Change From Baseline in the Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ(S)) Score at Endpoint for Patients >=18 Years Old(Day 1 (predose, baseline), end of trial (up to week 12))
- Kaplan-Meier Estimates for Time to 15% and 12% Improvement From Baseline in FEV1 Postdose on Day 1(Day 1 of the Treatment Period (predose and postdose))
- Change From Baseline in the Weekly Average of the Daily Morning Trough Peak Expiratory Flow (PEF) Over the 12 Week Treatment(Days -6 to Day 1 (predose, baseline), Day 1 (postdose) daily until Week 12)
- Change From Baseline in the Weekly Average of the Total Daily Asthma Symptom Score Over the 12-Week Treatment Period(Days -6 to Day 1 (predose, baseline), to Week 12)
- Change From Baseline in the Weekly Average of the Total Daily (24-hour) Use of Albuterol/Salbutamol Inhalation Aerosol Over the 12-Week Treatment Period(Days -6 to Day 1 (predose, baseline), up to week 12)
- Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period(Day 1 to Week 12 of the Treatment Period)
- Kaplan-Meier Estimate of Probability of Remaining in Study At Week 12(up to Week 12 of the Treatment Period)