A 6-Week Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Safety and Efficacy Study of the Potential Inhibitory Effects on the Hypothalamic-Pituitary-Adrenal Axis of Ciclesonide HFA Nasal Aerosol and Ciclesonide Aqueous Nasal Spray in Subjects 12 Years and Older With Perennial Allergic Rhinitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 310
- 试验地点
- 6
- 主要终点
- Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-24h) at Baseline
研究概览
简要总结
To demonstrate the effects of ciclesonide applied as a nasal aerosol and ciclesonide aqueous (AQ) nasal spray on hypothalamic-pituitary-adrenal axis.
详细描述
This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, safety and efficacy study of the effects of ciclesonide HFA nasal aerosol and ciclesonide AQ nasal spray on the HPA axis, when administered once daily to male and female subjects 12 years or older diagnosed with Perennial Allergic Rhinitis (PAR). The study consists of a screening period, a single blind run in period, a 6 week double blind treatment period including an active control segment, and a follow up period.
Placebo was used as the control during the double-blind treatment period for both delivery methods (HFA nasal aerosol and aqueous nasal spray)and for the study outcome analyses. There was also a positive control administered to a subset of these placebo subjects during the last 4 days of Week 6 (dexamethasone placebo or dexamethasone 6 mg). The active control was utilized to validate the assay sensitivity (ie, distinguish an effective from an ineffective drug) of this study, as dexamethasone is a known HPA axis suppressant, therefore this subset of placebo subjects was not included in the study outcome analyses.
This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Give written informed consent and assent, including privacy authorization as well as adherence to concomitant medication withholding periods, prior to participation.
- •Subject must be in general good health (defined as the absence of any clinically relevant abnormalities as determined by the Investigator) based on screening physical examination, medical history, and clinical laboratory values (Hematology, Chemistries and Urinalysis).
- •If any of the screening Hematology, Chemistries, or Urinalysis are not within the clinical laboratory's reference range, then the subject can be included only if the Investigator judges the deviations to be not clinically significant.
- •A history of PAR to a relevant perennial allergen (house dust mites, cockroach, molds, animal dander) for a minimum of two years immediately preceding the study Screening visit. The PAR must have been of sufficient severity to have required treatment (either continuous or intermittent) in the past and require treatment throughout the entire study period.
- •A demonstrated sensitivity to at least one allergen known to induce PAR (house dust mite, animal dander, cockroach, and molds) based on a documented result with a standard skin-prick test either within 90 days prior to screening or performed at the Screening visit. A positive test is defined as a wheal diameter at least 3 mm larger than the negative control wheal for the skin prick test. The subject's positive allergen test must be consistent with the medical history of PAR and must be present in the subject's environment throughout the study.
- •Subject, if female, must have a negative serum pregnancy test at screening. Females of childbearing potential must be instructed to and agree to avoid pregnancy during the study and must use an acceptable method of birth control.
- •An oral contraceptive, an intrauterine device (IUD), implantable contraceptive, transdermal or injectable contraceptive for at least 1 month prior to entering the study with continued use throughout the study and for thirty days following study participation.
- •Barrier method of contraception, eg, condom and/or diaphragm with spermicide while participating in the study.
- •Abstinence.
排除标准
- •Female subject who is pregnant or lactating.
- •History of physical findings of nasal pathology, including nasal polyps or other clinically significant respiratory tract malformations; recent nasal biopsy; nasal trauma; or nasal ulcers or perforations. Surgery and atrophic rhinitis or rhinitis medicamentosa are not permitted within the last 120 days prior to the Screening visit.
- •Subject is, in the investigator's judgement, having a seasonal exacerbation at the time of screening.
- •Participation in any investigational drug trial within the 30 days preceding the Screening visit or planned participation in another investigational drug trial at any time during this trial.
- •A known hypersensitivity to any corticosteroid or any of the excipients in the formulation of ciclesonide.
- •History of a respiratory infection or disorder [including, but not limited to bronchitis, pneumonia, influenza, severe acute respiratory syndrome (SARS)] within the 14 days preceding the Screening visit.
- •History of alcohol or drug abuse within 2 years preceding the Screening visit.
- •History of a positive test for HIV, hepatitis B or hepatitis C.
- •Active asthma requiring treatment with inhaled or systemic corticosteroids and/or routine use of beta agonists and any controller drugs (eg, theophylline, leukotriene antagonists, etc.); intermittent use (less than or equal to 3 uses per week) of inhaled short acting beta-agonists is acceptable. Use of short acting beta-agonists for exercise-induced bronchospasm will be allowed.
- •Expected use of any disallowed concomitant medications during the treatment period.
- •Initiation of immunotherapy during the study period or dose escalation during the study period. However, initiation of immunotherapy 90 days or more prior to the Screening Visit and use of a stable (maintenance) dose (30 days or more) may be considered for inclusion.
- •Previous randomization in an intranasal ciclesonide HFA nasal aerosol study.
- •Non-vaccinated exposure to or active infection with, chickenpox or measles within the 21 days preceding the Screening Visit.
- •Initiation of pimecrolimus cream 1% or greater or tacrolimus ointment 0.03% or greater during the study period or planned dose escalation during the study period. However, initiation of these creams/ointments 30 days or more prior to screening and use of a stable (maintenance) dose during the study period may be considered for inclusion.
- •Study participation by clinical investigator site employees and/or their immediate relatives who reside in the same household.
- •Study participation by more than one subject from the same household.
- •Have any of the following conditions that are judged by the investigator to be clinically significant and/or affect the subject's ability to participate in the clinical trial: impaired hepatic function including alcohol related liver disease or cirrhosis; history of ocular disturbances, eg, glaucoma or posterior subcapsular cataracts; any systemic infection hematological, hepatic, renal, endocrine (except for controlled diabetes mellitus or postmenopausal symptoms or hypothyroidism; gastrointestinal disease; malignancy (excluding basal cell carcinoma); current neuropsychological condition with or without drug therapy
- •Any condition that, in the judgment of the investigator, would preclude the subject from completing the protocol with capture of the assessments as written.
研究组 & 干预措施
Ciclesonide HFA Nasal Aerosol 320 mcg
Ciclesonide HFA Nasal Aerosol 320 mcg once daily
干预措施: Ciclesonide HFA Nasal Aerosol 320 mcg (Drug)
Ciclesonide HFA Nasal Aerosol 160 mcg
Ciclesonide HFA Nasal Aerosol 160 mcg once daily
干预措施: Ciclesonide HFA Nasal Aerosol 160 mcg (Drug)
HFA Nasal Aerosol placebo
HFA Nasal Aerosol Placebo once daily
干预措施: HFA Nasal Aerosol placebo (Drug)
Ciclesonide Aqueous Nasal Spray 200 mcg
Ciclesonide Aqueous Nasal Spray 200 mcg once daily
干预措施: Ciclesonide Aqueous Nasal Spray 200 mcg (Drug)
AQ Nasal Spray Placebo
AQ Nasal Spray Placebo once daily
干预措施: AQ Nasal Spray Placebo (Drug)
Placebo HFA plus Dexamethasone 6 mcg
Placebo HFA plus Dexamethasone 6 mg once daily
干预措施: Placebo plus Dexamethasone HFA (Drug)
Placebo AQ plus Dexamethasone 6 mg
Placebo AQ plus Dexamethasone 6 mg once daily
干预措施: Placebo AQ plus Dexamethasone 6 mg (Drug)
结局指标
主要结局
Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-24h) at Baseline
时间窗: Baseline
AUC(0-24h) will be computed using the linear trapezoidal rule based on the actual time of serum cortisol drawing. AUC(0-24) is then approximated by the sum of the areas of trapezoids. The trapezoid for each time interval is based on the actual times of non-missing cortisol values, and is defined by the actual time interval as the base, the line connecting the two cortisol values, and the two vertical sides at the two time points. Raw data is presented for baseline values (i.e. mean/SD), while inferential statistics are presented for week 6 values (i.e. LS mean/SE).
The Change in Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-24h) From Baseline to Week 6 of the Double Blind Treatment Period
时间窗: week 6
Change is calculated as week 6 minus baseline. AUC(0-24h) will be computed using the linear trapezoidal rule based on the actual time of serum cortisol drawing. AUC(0-24) is then approximated by the sum of the areas of trapezoids. The trapezoid for each time interval is based on the actual times of non-missing cortisol values, and is defined by the actual time interval as the base, the line connecting the two cortisol values, and the two vertical sides at the two time points. Raw data is presented for baseline values (i.e. mean/SD), while inferential statistics are presented for week 6 values (i.e. LS mean/SE).
次要结局
- Number of Subjects Experiencing Adverse Events (AEs)(Weeks 0-6)
- Percentage of Subjects Experiencing Adverse Events (AEs)(Weeks 0-6)
- Number of Subjects Experiencing Serious Adverse Events (SAEs).(Weeks 0-6)
- Percentage of Subjects Experiencing Serious Adverse Events (SAEs).(Weeks 0-6)
- Number of Subjects Who Discontinue Due to AEs(Weeks 0-6)
- Percentage of Subjects Who Discontinue Due to AEs(Weeks 0-6)
- Number of Subjects Experiencing Local Nasal AEs(Weeks 0-6)
- Percentage of Subjects Experiencing Local Nasal AEs(Weeks 0-6)
- Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-12h) at Baseline(Baseline)
- Change in Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-12h) From Baseline After 6 Weeks of Treatment(Weeks 0-6)
- Serum Cortisol Area Under the Concentration-time Curve (AUC)(12-24h) at Baseline(Baseline)
- Change in Serum Cortisol Area Under the Concentration-time Curve (AUC)(12-24h) From Baseline After 6 Weeks of Treatment(Weeks 0-6)
- Baseline Daily Subject-reported AM Reflective TNSS(Baseline)
- Change From Baseline in Daily Subject-reported AM Reflective TNSS Averaged Over the 6 Weeks of Double-blind Treatment(Weeks 0-6)
- Baseline Daily Subject-reported PM Reflective TNSS(Baseline)
- Change From Baseline in Daily Subject-reported PM Reflective TNSS Averaged Over the 6 Weeks of Double-blind Treatment(Weeks 0-6)
- Baseline Daily Subject-reported AM Instantaneous TNSS(Baseline)
- Change From Baseline in Daily Subject-reported AM Instantaneous TNSS Averaged Over the 6 Weeks of Double-blind Treatment(Weeks 0-6)
- Baseline Daily Subject-reported AM and PM Reflective TNSS(Baseline)
- Change From Baseline in Daily Subject-reported AM and PM Reflective TNSS Averaged Over Each Week, and Averaged Over the 6 Weeks of Double-blind Treatment(Weeks 0-6)
- Baseline Daily Subject-reported PM Instantaneous TNSS(Baseline)
- Change From Baseline in Daily Subject-reported PM Instantaneous TNSS Averaged Over the 6 Weeks of Double-blind Treatment(Weeks 0-6)
- Baseline Daily Subject-reported AM and PM Instantaneous TNSS(Baseline)
- Baseline Daily Subject-reported Individual AM Reflective NSS(Baseline)
- Change From Baseline in Daily Subject-reported Individual AM Reflective NSS Averaged Over the 6 Weeks of Double-blind Treatment Period(Weeks 0-6)
- Baseline Daily Subject-reported Individual PM Reflective NSS(Baseline)
- Change From Baseline in Daily Subject-reported AM and PM Instantaneous TNSS Averaged Over the 6 Weeks of Double-blind Treatment(Weeks 0-6)
- Change From Baseline in Daily Subject-reported Individual PM Reflective NSS Averaged Over the 6 Weeks of Double-blind Treatment Period(Weeks 0-6)
- Baseline Daily Subject-reported Individual AM and PM Reflective NSS(Baseline)
- Change From Baseline in Daily Subject-reported Individual AM and PM Reflective NSS Averaged Over the 6 Weeks of Double-blind Treatment Period(Weeks 0-6)
- Baseline Daily Subject-reported Individual AM Instantaneous NSS(Baseline)
- Baseline Daily Subject-reported Individual PM Instantaneous NSS(Baseline)
- Change From Baseline in Daily Subject-reported Individual PM Instantaneous NSS Averaged Over the 6 Weeks of Double-blind Treatment(Weeks 0-6)
- Baseline Daily Subject-reported Individual AM and PM Instantaneous NSS(Baseline)
- Change From Baseline in Daily Subject-reported Individual AM and PM Instantaneous NSS Averaged Over the 6 Weeks of Double-blind Treatment(Weeks 0-6)
- Time to Maximal Effect Over 6 Weeks of Double-blind Treatment.(Weeks 0-6)
- Ratio (Percentage) of Correct Advances of the Dose Indicator Out of Expected Advances.(Weeks 1-2, 2-4)
- Number of Devices With Actuation Consistency(Weeks 1-4)
- Percentage of Devices With Actuation Consistency(Weeks 1-4)
- Number of Devices With Major Discrepancies(Week 6)
- Percentage of Devices With Major Discrepancies(Week 6)
- Change From Baseline in Daily Subject-reported Individual AM Instantaneous NSS Averaged Over the 6 Weeks of Double-blind Treatment(Weeks 0-6)