Study of an Investigational Nasal Aerosol or Placebo Nasal Aerosol in Children (Ages 6-11) With Seasonal Allergies

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01307319
• Collaborator: (none)
• Enrollment: 715
• Locations: 45
• Arms: 3
• Duration (Months): 5
• Patients Per Site: 15.9
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and efficacy of an investigational nasal aerosol at two doses compared with placebo nasal aerosol in the treatment of seasonal allergic rhinitis in children (6-11 years of age).

Condition or Disease	Intervention/Treatment	Phase
Seasonal Allergic Rhinitis; SAR	Drug: BDP HFA; Drug: Placebo nasal aerosol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 715 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Study of Two Doses of an Investigational Nasal Aerosol Placebo Nasal Aerosol in Children (Ages 6-11) With Seasonal Allergies
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BDP HFA 80 mcg/day Participants/parents administer 40 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days.	Drug: BDP HFA; BDP (beclomethasone dipropionate) HFA (hydrofluoroalkane) nasal aerosol administered as a single actuation in each nostril daily for the 15 day treatment period. Each actuation contains either 40 or 80 mcg for a total daily dose of either 80 or 160 mcg depending upon the assigned treatment arm.; Other Names: BDP (beclomethasone dipropionate) HFA (hydrofluoroalkane) Nasal Aerosol QNASL®
Experimental: BDP HFA 160 mcg/day Participants/parents administer 80 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days.	Drug: BDP HFA; BDP (beclomethasone dipropionate) HFA (hydrofluoroalkane) nasal aerosol administered as a single actuation in each nostril daily for the 15 day treatment period. Each actuation contains either 40 or 80 mcg for a total daily dose of either 80 or 160 mcg depending upon the assigned treatment arm.; Other Names: BDP (beclomethasone dipropionate) HFA (hydrofluoroalkane) Nasal Aerosol QNASL®
Placebo Comparator: Placebo nasal aerosol once daily Participants/parents administer placebo (a spray with no medication in each nostril) once daily for 15 days.	Drug: Placebo nasal aerosol; Placebo formulated as a nasal aerosol spray and administered as a single actuation in each nostril daily for the 15 day treatment period.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) During the Two Weeks of Treatment [Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Day 15]

   Reflective TNSS is an evaluation of symptom severity over the past 12 hours prior to the recording of the score. Participants (with assistance from parents/guardians/caregivers, as needed) assessed and recorded four nasal symptoms (runny nose, nasal congestion, nasal itching, and sneezing) twice daily (AM and PM) using the following scale: 0 = absent (no sign/symptom present) 1 = mild (sign/symptom clearly present, but minimal awareness; easily tolerated) 2 = moderate (definite awareness of sign/symptom that is bothersome but tolerable) 3 = severe (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping) The total TNSS scale was 0-12 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. Baseline was defined as the average AM and PM subject-reported rTNSS over the 4 days prior to randomization.

Secondary Outcome Measures

1. Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) During the Two Weeks of Treatment [Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Day 15]

   Instantaneous TNSS is an evaluation of symptom severity over the last 10 minutes prior to the recording of the score. Participants (with assistance from parents/guardians/caregivers, as needed) assessed and recorded four nasal symptoms (runny nose, nasal congestion, nasal itching, and sneezing) twice daily (AM and PM) using the following scale: 0 = absent (no sign/symptom present) 1 = mild (sign/symptom clearly present, but minimal awareness; easily tolerated) 2 = moderate (definite awareness of sign/symptom that is bothersome but tolerable) 3 = severe (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping) The total TNSS scale was 0-12 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. Baseline was defined as the average AM and PM subject-reported iTNSS over the 4 days prior to randomization.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female subjects 6 to 11 years of age, as of the Screening Visit (SV)

• A documented history of SAR to a relevant seasonal allergen (tree/grass pollen) for a minimum of two years immediately preceding the study Screening Visit (SV).

• A demonstrated sensitivity to at least one seasonal allergen (tree/grass pollen) known to induce SAR through a standard skin prick test.

• Other criteria apply

Exclusion Criteria:

• History of physical findings of nasal pathology, including nasal polyps or other clinically significant respiratory tract malformations, recent nasal biopsy, nasal trauma (e.g., nasal piercing) or surgery, atrophic rhinitis, or rhinitis medicamentosa (all within the last 60 days prior to the Screening Visit [SV])

• History of a respiratory infection or disorder (including, but not limited to bronchitis, pneumonia, chronic sinusitis or influenza,) within the 14 days preceding the Screening Visit (SV), or development of a respiratory infection during the Run-in Period.

• Active asthma requiring treatment with inhaled or systemic corticosteroids and/or routine use of beta-agonists and any controller drug (e.g., theophylline, leukotriene antagonists). History of intermittent use (less than or equal to 3 uses per week) of inhaled short acting beta-agonists prior to the Screening Visit (SV) is acceptable

• Have any conditions that are judged by the investigator to be clinically significant and/or affect the subject's ability to participate in the clinical trial

• Other criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Clinical Study Site	Oxford	Alabama	United States	36203
2	Teva Clinical Study Site	Bell	California	United States	90201
3	Teva Clinical Study Site	Costa Mesa	California	United States	92626
4	Teva Clinical Study Site	Mission Viejo	California	United States	92691
5	Teva Clinical Study Site	Orange	California	United States	92868
6	Teva Clinical Study Site	Paramount	California	United States	90723
7	Teva Clinical Study Site	San Diego	California	United States	92120
8	Teva Clinical Study Site	San Diego	California	United States	92123
9	Teva Clinical Study Site	Stockton	California	United States	95207
10	Teva Clinical Study Site	Centennial	Colorado	United States	80112
11	Teva Clinical Study Site	Colorado Springs	Colorado	United States	80907
12	Teva Clinical Study Site	Gainesville	Georgia	United States	30501
13	Teva Clinical Study Site	Lawrenceville	Georgia	United States	30046
14	Teva Clinical Study Site	Savannah	Georgia	United States	31406
15	Teva Clinical Study Site	Stockbridge	Georgia	United States	30281
16	Teva Clinical Study Site	Indianapolis	Indiana	United States	43208
17	Teva Clinical Study Site	Bethesda	Maryland	United States	20814
18	Teva Clinical Study Site	Minneapolis	Minnesota	United States	55402
19	Teva Clinical Study Site	Plymouth	Minnesota	United States	55441
20	Teva Clinical Study Site	Columbia	Missouri	United States	65203
21	Teva Clinical Study Site	Rolla	Missouri	United States	65401
22	Teva Clinical Study Site	Warrensburg	Missouri	United States	64093
23	Teva Clinical Study Site	Bozeman	Montana	United States	597158
24	Teva Clinical Study Site	Brick	New Jersey	United States	08724
25	Teva Clinical Study Site	High Point	North Carolina	United States	27262
26	Teva Clinical Study Site	Oklahoma City	Oklahoma	United States	73102
27	Teva Clinical Study Site	Portland	Oregon	United States	97213
28	Teva Clinical Study Site	Blue Bell	Pennsylvania	United States	19422
29	Teva Clinical Study Site	Collegeville	Pennsylvania	United States	19426
30	Teva Clinical Study Site	Philadelphia	Pennsylvania	United States	19115
31	Teva Clinical Study Site	Pittsburgh	Pennsylvania	United States	15241
32	Teva Clinical Study Site	Charleston	South Carolina	United States	20460
33	Teva Clinical Study Site	Orangeburg	South Carolina	United States	29119
34	Teva Clinical Study Site	Austin	Texas	United States	78731
35	Teva Clinical Study Site	Dallas	Texas	United States	75230
36	Teva Clinical Study Site	Dallas	Texas	United States	75246
37	Teva Clinical Study Site	El Paso	Texas	United States	79903
38	Teva Clinical Study Site	Ft. Worth	Texas	United States	76132
39	Teva Clinical Study Site	Houston	Texas	United States	77054
40	Teva Clinical Study Site	Kerrville	Texas	United States	78028
41	Teva Clinical Study Site	New Braunfels	Texas	United States	78130
42	Teva Clinical Study Site	San Antonio	Texas	United States	78229
43	Teva Clinical Study Site	Waco	Texas	United States	76712
44	Teva Clinical Study Site	Burke	Virginia	United States	22015
45	Teva Clinical Study Site	Richmond	Virginia	United States	23233

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT01307319
• Other Study ID Numbers: BDP-AR-305
• First Posted: Mar 2, 2011
• Last Update Posted: Feb 20, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.: Allergies; Hayfever
• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Hypersensitivity; Beclomethasone

Study Results

Participant Flow

Pre-assignment Detail	A total of 1026 subjects were screened and 906 were enrolled and participated in the Run-in Period. Of the 906 enrolled subjects, 715 were randomized to treatment.

Arm/Group Title	BDP HFA 80 mcg/Day	BDP HFA 160 mcg/Day	Placebo Nasal Aerosol Once Daily
Arm/Group Description	Participants/parents administer 40 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days.	Participants/parents administer 80 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days.	Participants/parents administer placebo (a spray with no medication in each nostril) once daily for 15 days.
Period Title: Overall Study
STARTED	239	242	234
Safety Population	239	241	234
ITT Population	238	241	234
COMPLETED	235	234	227
NOT COMPLETED	4	8	7

Baseline Characteristics

Arm/Group Title	BDP HFA 80 mcg/Day	BDP HFA 160 mcg/Day	Placebo Nasal Aerosol Once Daily	Total
Arm/Group Description	Participants/parents administer 40 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days.	Participants/parents administer 80 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days.	Participants/parents administer placebo (a spray with no medication in each nostril) once daily for 15 days.	Total of all reporting groups
Overall Participants	239	241	234	714
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.9 (1.73)	9.1 (1.62)	9.1 (1.65)	9.0 (1.67)
Sex: Female, Male (Count of Participants)
Female	105 43.9%	116 48.1%	111 47.4%	332 46.5%
Male	134 56.1%	125 51.9%	123 52.6%	382 53.5%
Race/Ethnicity, Customized (participants) [Number]
White	169 70.7%	172 71.4%	164 70.1%	505 70.7%
Black or African American	56 23.4%	55 22.8%	52 22.2%	163 22.8%
Asian	2 0.8%	4 1.7%	6 2.6%	12 1.7%
Other	12 5%	10 4.1%	12 5.1%	34 4.8%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	40 16.7%	53 22%	45 19.2%	138 19.3%
Not Hispanic or Latino	199 83.3%	188 78%	189 80.8%	576 80.7%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	19.0 (4.15)	19.4 (4.52)	19.1 (4.72)	19.1 (4.46)

Outcome Measures

1. Secondary Outcome

Title	Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) During the Two Weeks of Treatment
Description	Instantaneous TNSS is an evaluation of symptom severity over the last 10 minutes prior to the recording of the score. Participants (with assistance from parents/guardians/caregivers, as needed) assessed and recorded four nasal symptoms (runny nose, nasal congestion, nasal itching, and sneezing) twice daily (AM and PM) using the following scale: 0 = absent (no sign/symptom present) 1 = mild (sign/symptom clearly present, but minimal awareness; easily tolerated) 2 = moderate (definite awareness of sign/symptom that is bothersome but tolerable) 3 = severe (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping) The total TNSS scale was 0-12 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. Baseline was defined as the average AM and PM subject-reported iTNSS over the 4 days prior to randomization.
Time Frame	Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Day 15

Outcome Measure Data

Analysis Population Description

The intent to treat (ITT) population included all randomized participants who received at least one dose of randomized study medication and had at least one post-baseline assessment. Two enrolled participants were excluded. One was randomized in error and did not receive test medication. The other provided no post-baseline assessment.

Arm/Group Title	BDP HFA 80 mcg/Day	BDP HFA 160 mcg/Day	Placebo Nasal Aerosol Once Daily
Arm/Group Description	Participants/parents administer 40 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days.	Participants/parents administer 80 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days.	Participants/parents administer placebo (a spray with no medication in each nostril) once daily for 15 days.
Measure Participants	238	241	234
Least Squares Mean (Standard Error) [units on a scale]	-1.6 (0.13)	-1.7 (0.13)	-1.0 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BDP HFA 80 mcg/Day, Placebo Nasal Aerosol Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	a priori statistical significance is <0.05.
	Method	mixed-model for repeated measures (MMRM)
	Comments	The MMRM included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.
Method of Estimation	Estimation Parameter	LSM treatment difference from placebo
	Estimated Value	-0.63
	Confidence Interval	(2-Sided) 95%; -1.0 to -0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BDP HFA 160 mcg/Day, Placebo Nasal Aerosol Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	a priori statistical significance is <0.05.
	Method	mixed-model for repeated measures (MMRM)
	Comments	The MMRM included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.
Method of Estimation	Estimation Parameter	LSM treatment difference from placebo
	Estimated Value	-0.73
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) During the Two Weeks of Treatment
Description	Reflective TNSS is an evaluation of symptom severity over the past 12 hours prior to the recording of the score. Participants (with assistance from parents/guardians/caregivers, as needed) assessed and recorded four nasal symptoms (runny nose, nasal congestion, nasal itching, and sneezing) twice daily (AM and PM) using the following scale: 0 = absent (no sign/symptom present) 1 = mild (sign/symptom clearly present, but minimal awareness; easily tolerated) 2 = moderate (definite awareness of sign/symptom that is bothersome but tolerable) 3 = severe (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping) The total TNSS scale was 0-12 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. Baseline was defined as the average AM and PM subject-reported rTNSS over the 4 days prior to randomization.
Time Frame	Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Day 15

Outcome Measure Data

Analysis Population Description

The intent to treat (ITT) population included all randomized participants who received at least one dose of randomized study medication and had at least one post-baseline assessment. Two enrolled participants were excluded. One was randomized in error and did not receive test medication. The other provided no post-baseline assessment.

Arm/Group Title	BDP HFA 80 mcg/Day	BDP HFA 160 mcg/Day	Placebo Nasal Aerosol Once Daily
Arm/Group Description	Participants/parents administer 40 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days.	Participants/parents administer 80 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days.	Participants/parents administer placebo (a spray with no medication in each nostril) once daily for 15 days.
Measure Participants	238	241	234
Least Squares Mean (Standard Error) [units on a scale]	-1.9 (0.14)	-2.0 (0.14)	-1.2 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BDP HFA 80 mcg/Day, Placebo Nasal Aerosol Once Daily
	Comments	The power calculation assumed the standard deviation (SD) for the change from baseline over two weeks in the average of AM and PM reflective TNSS is assumed to be 2.0. Using this standard deviation, 235 subjects per arm provides 90% power to detect a difference of 0.60 in TNSS change from baseline between treatment groups with a two-sided alpha level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	a priori statistical significance is <0.05.
	Method	mixed-model for repeated measures (MMRM)
	Comments	The MMRM included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.
Method of Estimation	Estimation Parameter	LSM treatment difference from placebo
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BDP HFA 160 mcg/Day, Placebo Nasal Aerosol Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	a priori statistical significance is <0.05.
	Method	mixed-model for repeated measures (MMRM)
	Comments	The MMRM included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.
Method of Estimation	Estimation Parameter	LSM treatment difference from placebo
	Estimated Value	-0.76
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Day 1 to Week 6
Arm/Group Title	BDP HFA 80 mcg/Day		BDP HFA 160 mcg/Day		Placebo Nasal Aerosol Once Daily
Arm/Group Description	Participants/parents administer 40 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days.		Participants/parents administer 80 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days.		Participants/parents administer placebo (a spray with no medication in each nostril) once daily for 15 days.
All Cause Mortality
	BDP HFA 80 mcg/Day		BDP HFA 160 mcg/Day		Placebo Nasal Aerosol Once Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	BDP HFA 80 mcg/Day		BDP HFA 160 mcg/Day		Placebo Nasal Aerosol Once Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/239 (0%)		0/241 (0%)		0/234 (0%)
Other (Not Including Serious) Adverse Events
	BDP HFA 80 mcg/Day		BDP HFA 160 mcg/Day		Placebo Nasal Aerosol Once Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/239 (0%)		0/241 (0%)		0/234 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.