E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rhinitis, Allergic, Perennial and/or Seasonal
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E.1.1.1 | Medical condition in easily understood language |
Rhinitis, Allergic, Perennial and/or Seasonal
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039085 |
E.1.2 | Term | Rhinitis allergic |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective was to evaluate the effect of a 6-week treatment with TAA-AQ (110 μg) and TAA-AQ (220 μg) once daily (QD) versus placebo on hypothalamic-pituitary-adrenal (HPA) axis function as measured by serum cortisol AUC(0-24 hr) in children (>=2 to <12 years old) with allergic rhinitis (AR).
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E.2.2 | Secondary objectives of the trial |
To evaluate the change from baseline in the overall total nasal symptom score (TNSS). This efficacy
variable could be
used as a surrogate measure of drug exposure
• To assess the safety of a 6-week treatment period with TAA-AQ versus placebo in children (≥2
to <12 years old) with
AR, through assessment of treatment-emergent adverse events (TEAEs) and vital signs
• To further characterize TAA-AQ on basal HPA axis function
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. History of AR documented by the investigator, as follows:
◦At least a 1-year clinical history (6-month history if the participant was >= 2 to < 4 years of age) of perennial allergic rhinitis (PAR); or a clinical history of seasonal allergic rhinitis (SAR) over 2 seasons and
◦positive skin test (prick or intradermal) to a seasonal or perennial allergen that was present in the participant's environment at time of screening.
2. Written informed consent and ability of parent/legal guardian of the participant to give a written informed consent before any study related procedures. Participants >=7 years of age (or younger according to the governing institutional review board [IRB]) had to provide a signed assent form
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E.4 | Principal exclusion criteria |
1. Concomitant medical condition that might have interfered with the administration of a nasal spray, including anatomical abnormalities of the nose, face (eg, polyposis, markedly deviated septum)
2. Presence of any active, untreated, or clinically significant musculoskeletal, endocrinologic, gastrointestinal, hepatic, respiratory, cardiovascular, or neurological condition that might have interfered with the study
3. Any conditions or treatment that might have affected the HPA axis or the plasma cortisol assay, including but not limited to:
◦Documented disorder involving the hypothalamus, pituitary, or adrenal gland
◦Current use of serotonergic, dopaminergic, adrenergic, cholinergic agonists and antagonists, opiates, immunomodulatory, hormonal drugs, and lipid-lowering agents
◦Treatment with systemic corticosteroids (oral, intravenous, intramuscular, or intra-articular) within 3 months prior to Visit 1
◦Treatment with systemic corticosteroids for > 2 courses received up to 1 year before Visit 1 was exclusionary. Up to 2 courses of systemic corticosteroids, each course not exceeding 14 days, up to 1 year before Visit 1 was allowed
◦Treatment with inhaled, intranasal, or high-potency topical corticosteroids within 6 weeks of Visit 1
◦History of hospitalization due to asthma within 1 year before screening. Participants with mild asthma that was well-controlled without the use of inhaled corticosteroids within 6 weeks prior to Visit 1 were eligible for the study
4. Any clinically significant (as determined by the investigator) abnormal laboratory test at Visit 1
5. Morning serum cortisol outside the reference range at Visit 1
6. Any of the following missing serum cortisol samples from the Visit-2 collection: first sample (before administration of investigational product), 20-hour sample, 24-hour sample, or any 2 consecutive samples
7. Any medical condition where use of corticosteroids might have been contraindicated or could have led to disease exacerbation (eg, glaucoma, cataract, ocular herpes simplex, tuberculosis, growth retardation)
8. History of hypersensitivity to corticosteroids or to the rescue medication, investigational product, or to any of their excipients
9. Unresolved upper respiratory tract infection, sinus infection, or nasal candidiasis (ie, symptomatic or under treatment) within the last 2 weeks prior to Visit 1 and Visit 3
10. Females of childbearing potential not protected by effective contraceptive method of birth control or were unwilling to abstain from sexual activity and/or, were unwilling or unable to test for pregnancy. Only female adolescent with onset of menses were to be checked by serum pregnancy test at Visit 1
11. Pregnant female adolescent (who tested positive for pregnancy at Visit 1) The above information was not intended to contain all considerations relevant to potential participation in a clinical trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
•Ratio of Serum Cortisol Area Under Curve [AUC(0-24 hr)] at the End of Treatment to Baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and 6 weeks post randomization (max D47) |
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E.5.2 | Secondary end point(s) |
1- Change From Baseline in the Reflective Total Nasal Symptom Score (rTNSS)
2- Number of Participants by Relief Level as Evaluated by the Physician
3- Number of Participants by Relief Level as Evaluated by the Participant
4- Number of Participants Using Rescue Medication
5- The Percent of Days of Rescue Medication Use During the Double-blind Treatment Phase
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - 8 to 24 days prerandomization up to 6 weeks
2,3- At end of study (max D50)
4-From 8 to 24 days prior randomization and randomization to end of study (max D50)
5- From randomization up to end of study (max D50) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |