Clinical trial NCT01378429: Safety Study of the Potential Inhibitory Effects of Ciclesonide Nasal Aerosol on the Hypothalamic-Pituitary-Adrenal Axis in Subjects 6-11 Years With Perennial Allergic Rhinitis
Official title: A 6-Week Randomized, Double-blind, Placebo-controlled, Parallel Group, Safety Study of the Potential Inhibitory Effects of Ciclesonide Nasal Aerosol on the Hypothalamic-Pituitary-Adrenal (HPA) Axis in Subjects 6-11 Years With Perennial Allergic Rhinitis (PAR)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Perennial Allergic Rhinitis
PAR
Keywords: Perennial Allergic Rhinitis
PAR
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2011-06-22
Enrollment: 89
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, safety study of the effects of ciclesonide nasal aerosol (74 mcg) on the HPA axis when administered once daily to male and premenarchal female subjects 6 to 11 years of age with a diagnosis of PAR.

Detailed description: This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, safety study of the effects of ciclesonide nasal aerosol (74 mcg) on the HPA axis when administered once daily to male and premenarchal female subjects 6 to 11 years of age with a diagnosis of PAR.

The study requires that subjects be domiciled during two 24- to 36-hour time periods for sample collection for serum and urinary free cortisol measurements, as well as PK evaluations (single \[predose\] time point during the first domiciled period, and 24-hour sampling during the second domiciled period).

Eligibility criteria: Inclusion Criteria:

* Gives written informed consent (parent/legal guardian) and assent (when appropriate, from the child), including privacy authorization as well as adherence to concomitant medication withholding periods, prior to participation.
* Is a male or premenarchal female 6 to 11 years old and ≥ 20 kg at the screening visit.
* Is in general good health (defined as the absence of any clinically relevant abnormalities as determined by the investigator) based on screening physical examination and medical history.
* Has a history of PAR to a relevant perennial allergen (house dust mites, cockroaches, molds, animal dander) for a minimum of one year 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.
* Has a demonstrated sensitivity to at least one allergen known to induce PAR (house dust mites, cockroaches, molds, and animal dander) based on a documented result with a standard skin-prick test either within one year prior to the screening visit 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 of PAR, and the allergen must be present in the subject's environment throughout the study.

Exclusion Criteria:

* Has a 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 120 days prior to the screening visit.
* Has evidence of infection, significant anatomic abnormality, ulceration of the mucosa, blood in the nose, or any other clinically relevant finding on nasal examination at the screening visit.
* Has nasal jewelry.
* Has participated in any investigational drug trial within the 30 days preceding the screening visit or is planning participation in another investigational drug trial at any time during this trial.
* Has a known hypersensitivity to any corticosteroid or any of the excipients in the formulation of ciclesonide.
* Has a history of a respiratory infection or disorder, including but not limited to bronchitis, pneumonia, influenza, and severe acute respiratory syndrome (SARS), within the 14 days preceding the screening visit.
* Has a history of adrenal insufficiency.
* Has active asthma requiring treatment with inhaled or systemic corticosteroids and/or routine use of beta-agonists and any controller drugs (eg, theophylline, leukotriene antagonists); intermittent use (≤ 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.
* Is expecting to use any disallowed concomitant medications during the treatment period.
* Is, in the investigator's judgment, having a seasonal exacerbation at the time of the screening visit.
* Is planning 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.
* Has nonvaccinated exposure to or active infection with chickenpox or measles within the 21 days preceding the screening visit.
* Initiates pimecrolimus cream 1% or greater or tacrolimus ointment 0.03% or greater during the study period or plans a 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.
* Has experienced significant blood loss within 60 days or loss of plasma within 72 hours prior to the screening visit or intends to undergo elective surgery within 30 days following end of study.
* Is a child or immediate relative of any clinical investigator or site personnel, even those who are not directly involved in this study.
* Resides in the same household as another subject who is participating in this study at the same time.
* Has any of the following conditions that are judged by the investigator to be clinically significant and/or to affect the subject's ability to participate in the clinical trial:

  * impaired hepatic function
  * history of ocular disturbances, eg, glaucoma or posterior subcapsular cataracts or herpes simplex
  * any systemic infection
  * hematological (including anemia), hepatic, renal, endocrine disease
  * gastrointestinal disease
  * malignancy (excluding basal cell carcinoma)
  * current neuropsychological condition with or without drug therapy. Any behavioral condition that could affect subject's ability to accurately report symptoms to the caregiver such as developmental delay, attention deficit disorder, and autism.
* Has any condition that, in the judgment of the investigator, would preclude the subject from completing the protocol with capture of the assessments as written.

Primary outcomes:
measure: The Change in Serum Cortisol Area Under the Curve (AUC) From Time 0 to 24 Hours (0-24), Calculated Using a Trapezoidal Rule, From Baseline to the End of the 6 Week Treatment Period
timeFrame: Week 0 and 6
Secondary outcomes:
measure: Change From Baseline in Urinary Free Cortisol-Corrected for Urine Creatinine
timeFrame: weeks 0-6
measure: Change From Baseline in Urinary Free Cortisol-Uncorrected for Urine Creatinine
timeFrame: weeks 0-6
measure: Number of Subjects Experiencing AEs
timeFrame: weeks 0-6
measure: Percentage of Subjects Experiencing AEs
timeFrame: weeks 0-6
measure: Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
timeFrame: weeks 0-6
measure: Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
timeFrame: weeks 0-6
measure: AUC(0-24h)
timeFrame: Week 6
measure: Maximum Observed Concentration
timeFrame: Week 6
measure: Time to the Occurrence of Cmax
timeFrame: Week 6
measure: Terminal Half Life (t1/2)
timeFrame: Weeks 6
measure: Apparent Clearance of the Drug (CL/F)
timeFrame: Week 6
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: Week 6
measure: Ratio (Percentage) of the Number of Correct Advances of the Dose Indicator to the Number of Expected Advances Based on Subject Self-report of Study Medication Administration Plus Extra Non-nasal Actuations
timeFrame: weeks 0-6
measure: Number of Devices With Actuation Consistency, Where Actuation Consistency is Defined as a Dose Indicator Count Within ± 20% of the Subject Self-report of Study Medication Administration
timeFrame: weeks 0-6
measure: Percentage of Devices With Actuation Consistency, Where Actuation Consistency is Defined as a Dose Indicator Count Within ± 20% of the Subject Self-report of Study Medication Administration
timeFrame: weeks 0-6
measure: Change From Baseline in Averaged Daily Subject-reported AM and PM Reflective TNSS Averaged Over the 6 Weeks of Double-blind Treatment
timeFrame: weeks 0-6
Other outcomes:
Locations:
city: Costa Mesa
country: United States
facility: West Coast Clinical Trials
state: California
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Normal
country: United States
facility: Sneeze, Wheeze, & Itch Associates, LLC
state: Illinois
city: Plymouth
country: United States
facility: Clinical Research Institute
state: Minnesota
city: El Paso
country: United States
facility: Western Sky Medical Research
state: Texas
city: New Braunfels
country: United States
facility: Central Texas Health Research
state: Texas
city: San Antonio
country: United States
facility: Sylvania Research Associates
state: Texas
Study officials:
References: