Trial Outcomes & Findings for Nasacort AQ Hypothalamic-Pituitary-Adrenal (HPA) Axis Study in Children With Allergic Rhinitis (NCT NCT01154153)

Last Updated: 2012-06-26

Results Overview

Blood samples were collected over a 24-hour period (at 0, 2, 4, 8, 12, 20, and 24 hours), with 0 hour being between 8:00AM to 9:00AM, immediately prior to investigational product (IP) administration. AUC (0-24hr) was calculated using the trapezoid rule, and was normalized by dividing the AUC(0-24 hr) by the actual sample collection interval between 0-hour and 24-hour blood draw times. Ratio in Serum Cortisol AUC(0-24 hr) = (Serum Cortisol AUC\[0-24 hr\] at 6 weeks postrandomization)/(Serum Cortisol AUC\[0-24 hr\] at 1-3 days prerandomization). Log transformation was used for the analysis.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

140 participants

Primary outcome timeframe

1-3 days prerandomization and 6 weeks postrandomization

Results posted on

2012-06-26

Participant Flow

The study was performed in 8 study centers in the United States.

179 participants were screened in this study. 31 participants were screen failures and 8 participants did not continue to as the limit on the number of participants to be randomized had been reached. 140 participants were randomized.

Participant milestones

Participant milestones
Measure	Placebo Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and placebo during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.	TAA-AQ Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and TAA-AQ (Nasacort AQ) during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.
Overall Study STARTED	71	69
Overall Study COMPLETED	66	66
Overall Study NOT COMPLETED	5	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and placebo during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.	TAA-AQ Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and TAA-AQ (Nasacort AQ) during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.
Overall Study Poor compliance to protocol	2	0
Overall Study Unable to use labs	2	3
Overall Study Withdrew consent	1	0

Baseline Characteristics

Nasacort AQ Hypothalamic-Pituitary-Adrenal (HPA) Axis Study in Children With Allergic Rhinitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=71 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and placebo during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.	TAA-AQ n=69 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and TAA-AQ (Nasacort AQ) during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.	Total n=140 Participants Total of all reporting groups
Age Continuous	7.3 years STANDARD_DEVIATION 2.7 • n=5 Participants	7.1 years STANDARD_DEVIATION 2.5 • n=7 Participants	7.2 years STANDARD_DEVIATION 2.6 • n=5 Participants
Age, Customized >=2 to < 4 years	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
Age, Customized >=4 to < 6 years	15 participants n=5 Participants	16 participants n=7 Participants	31 participants n=5 Participants
Age, Customized >=6 to < 12 years	50 participants n=5 Participants	48 participants n=7 Participants	98 participants n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	28 Participants n=7 Participants	57 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	41 Participants n=7 Participants	83 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	22 participants n=5 Participants	22 participants n=7 Participants	44 participants n=5 Participants
Race/Ethnicity, Customized White	43 participants n=5 Participants	42 participants n=7 Participants	85 participants n=5 Participants
Race/Ethnicity, Customized Others	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment United States	71 participants n=5 Participants	69 participants n=7 Participants	140 participants n=5 Participants
Tanner Classification Stage 1	55 Participants n=5 Participants	60 Participants n=7 Participants	115 Participants n=5 Participants
Tanner Classification Stage 2	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Tanner Classification Stage 3	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Tanner Classification Stage 4	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Tanner Classification Stage 5	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Primary Allergic Rhinitis (AR) diagnosis PAR only	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Primary Allergic Rhinitis (AR) diagnosis SAR only	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Primary Allergic Rhinitis (AR) diagnosis Both PAR and SAR	55 Participants n=5 Participants	54 Participants n=7 Participants	109 Participants n=5 Participants
Time from the first Allergic Rhinitis symptom to Visit 1	4.82 Years STANDARD_DEVIATION 2.70 • n=5 Participants	4.79 Years STANDARD_DEVIATION 2.48 • n=7 Participants	4.80 Years STANDARD_DEVIATION 2.59 • n=5 Participants

PRIMARY outcome

Timeframe: 1-3 days prerandomization and 6 weeks postrandomization

Population: The per protocol (PP) population included all randomized participants who took at least one dose of study medication and had no major protocol violations. Major protocol violations were those deemed most likely to affect the interpretation of the results and included poor compliance, use of prohibited medication, missing blood samples.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and placebo during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.	TAA-AQ n=65 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and TAA-AQ (Nasacort AQ) during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.
Ratio of Serum Cortisol Area Under Curve [AUC(0-24 hr)] at the End of Treatment to Baseline	0.938 Ratio Interval 0.39 to 1.63	0.898 Ratio Interval 0.48 to 4.45

SECONDARY outcome

Timeframe: From 8-24 days prerandomization up to 6 weeks postrandomization

Every morning, participants rated the severity of symptoms experienced over the previous 24 hours using scale from 0-3, where 0=symptoms absent, 1=mild, 2=moderate, and 3=severe symptoms (interfere with daily living or sleep) for each symptom (nasal congestion, nasal itching, sneezing, and runny nose). The rTNSS was the sum of the individual symptom scores, ranged from 0-12 (where 12 reflected the worst symptoms). Change from baseline in the rTNSS = mean rTNSS (double-blind treatment phase) - mean rTNSS (screening phase).

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and placebo during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.	TAA-AQ n=65 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and TAA-AQ (Nasacort AQ) during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.
Change From Baseline in the Reflective Total Nasal Symptom Score (rTNSS)	-0.22 Score on a scale Standard Deviation 1.12	-1.07 Score on a scale Standard Deviation 1.66

SECONDARY outcome

Timeframe: At end of study (43-50 days after randomization)

Efficacy of treatment was assessed by the physician using a scale from 0-4 for relief levels, where 0 = no relief (symptoms unchanged or worsened than before), 1 = slight relief (symptoms present and only minimally improved), 2 = moderate relief (symptoms are present and may be troublesome, but are noticeably improved), 3 = marked relief (symptoms are greatly improved and although present are scarcely troublesome) and 4 = complete relief (virtually no symptom present).

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and placebo during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.	TAA-AQ n=65 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and TAA-AQ (Nasacort AQ) during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.
Number of Participants by Relief Level as Evaluated by the Physician Relief Level 2 (Moderate relief)	16 Participants	20 Participants
Number of Participants by Relief Level as Evaluated by the Physician Relief Level 0 (No relief)	11 Participants	9 Participants
Number of Participants by Relief Level as Evaluated by the Physician Relief Level 1 (Slight relief)	18 Participants	13 Participants
Number of Participants by Relief Level as Evaluated by the Physician Relief Level 3 (Marked relief)	13 Participants	17 Participants
Number of Participants by Relief Level as Evaluated by the Physician Relief Level 4 (Complete relief)	3 Participants	6 Participants

SECONDARY outcome

Timeframe: At end of study (43-50 days after randomization)

Efficacy of treatment was assessed by the participant using a scale from 0-4 for relief levels, where 0 = no relief (symptoms unchanged or worsened than before), 1 = slight relief (symptoms present and only minimally improved), 2 = moderate relief (symptoms are present and may be troublesome, but are noticeably improved), 3 = marked relief (symptoms are greatly improved and although present are scarcely troublesome) and 4 = complete relief (virtually no symptom present).

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and placebo during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.	TAA-AQ n=65 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and TAA-AQ (Nasacort AQ) during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.
Number of Participants by Relief Level as Evaluated by the Participant Relief level 0 (No relief)	9 Participants	5 Participants
Number of Participants by Relief Level as Evaluated by the Participant Relief level 1 (Slight relief)	17 Participants	22 Participants
Number of Participants by Relief Level as Evaluated by the Participant Relief level 2 (Moderate relief)	16 Participants	13 Participants
Number of Participants by Relief Level as Evaluated by the Participant Relief level 3 (Marked relief)	14 Participants	16 Participants
Number of Participants by Relief Level as Evaluated by the Participant Relief level 4 (Complete relief)	5 Participants	9 Participants

SECONDARY outcome

Timeframe: From 8 to 24 days prerandomization and randomization to end of study (43-50 days postrandomization)

The number of participants using the rescue medication (Claritin®) during the single-blind screening phase (the time from 8-24 days before randomization up to the day before randomization) and during the double-blind treatment phase (the time from randomization to end of study).

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and placebo during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.	TAA-AQ n=65 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and TAA-AQ (Nasacort AQ) during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.
Number of Participants Using Rescue Medication Prerandomization period	8 Participants	8 Participants
Number of Participants Using Rescue Medication Postrandomization period	24 Participants	19 Participants

SECONDARY outcome

Timeframe: From randomization to 43-50 days postrandomization

The percent of days of rescue medication used during the double-blind treatment phase was calculated. For participants who did not use any rescue medication, the percentage of days using rescue medication was set to be 0.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and placebo during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.	TAA-AQ n=65 Participants Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and TAA-AQ (Nasacort AQ) during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.
The Percent of Days of Rescue Medication Use During the Double-blind Treatment Phase	4.02 Percentage of days Standard Deviation 12.77	3.07 Percentage of days Standard Deviation 11.82

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

TAA-AQ

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=71 participants at risk Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and placebo during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.	TAA-AQ n=69 participants at risk Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and TAA-AQ (Nasacort AQ) during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.
Injury, poisoning and procedural complications Humerus fracture	1.4% 1/71	0.00% 0/69

Other adverse events

Other adverse events
Measure	Placebo n=71 participants at risk Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and placebo during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.	TAA-AQ n=69 participants at risk Children \>=2 to \<12 years old with AR symptoms who received placebo during the screening phase and TAA-AQ (Nasacort AQ) during the treatment phase. All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.
Nervous system disorders Headache	5.6% 4/71	2.9% 2/69
Respiratory, thoracic and mediastinal disorders Epistaxis	9.9% 7/71	4.3% 3/69
General disorders Pyrexia	2.8% 2/71	5.8% 4/69

Additional Information

Trial Transparency Team

sanofi-aventis

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator shall have the right to independently publish study results from his site after a multicenter publication, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication for review and comment at least 45 days (for abstracts -20 days) in advance of any submission for publication. The Sponsor may request for the publication to be delayed for a limited time, not to exceed 90 days to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER